Nutrient chapter

Shikimic acid

A nonaromatic plant and microbial metabolite connecting chorismate biosynthesis, cofactor requirements, microbial vitamin precursors and context-specific mammalian experimental responses.

129 recorded mechanisms · 8 availability situations · 1 preserved sources. Source recording and scientific verification are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Shikimate is the carboxylate conjugate base of shikimic acid, with the same stereochemical scaffold.
Shikimic acid → Shikimate anion Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Authoritative chemical identity/property records, PUG REST properties retrieved; not a biological experiment. Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Chemical identity records; acid-base relation rather than a therapeutic effect.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
Shikimate is the carboxylate conjugate base of shikimic acid, with the same stereochemical scaffold.
primary_references
PubChem shikimic acid CID 8742 and shikimate CID 7057976 | 2026 | https://pubchem.ncbi.nlm.nih.gov/compound/8742 | https://pubchem.ncbi.nlm.nih.gov/compound/7057976
primary_references
The metabolism of shikimate in the rat. | 1978 | DOI 10.1042/bj1700257 | PMID 637841 | https://pubmed.ncbi.nlm.nih.gov/637841/ | https://doi.org/10.1042/bj1700257 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1183892/
source_locator
Reviewed reference lines 5-5; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 5–5
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Chemical identity records; acid-base relation rather than a therapeutic effect. · Recorded from source · Recorded from source
**One chemical scaffold, two protonation states.** Shikimic acid is (3R,4S,5R)-3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acid, C7H10O5, molecular mass 174.15 g/mol. Its ring is not aromatic, so calling it a phenolic compound is chemically misleading even when a paper does so. Shikimate is its carboxylate conjugate base (C7H9O5−); charge is meaningful, but these must remain connected identities. Neither is oseltamivir, anisatin, triacetylshikimic acid or 3,4-O-isopropylidene shikimic acid. Plants and many microorganisms use the biosynthetic pathway; humans have no complete endogenous shikimate pathway. Absence of that pathway does not mean an ingested molecule cannot be absorbed or metabolized by the host–microbiome system. [PubChem shikimic acid CID 8742 and shikimate CID 7057976](https://pubchem.ncbi.nlm.nih.gov/compound/8742) [The metabolism of shikimate in the rat.](https://pubmed.ncbi.nlm.nih.gov/637841/)
Complete structured claim and evidence
DAHP synthase combines PEP and erythrose-4-phosphate into DAHP.
Phosphoenolpyruvate / PEP → 3-Deoxy-D-arabino-heptulosonate 7-phosphate / DAHP Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction. Primary correction read: duplicated Fig. 7 and incorrect panel reference corrected; not a retraction.
experimental_model
Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
DAHP synthase combines PEP and erythrose-4-phosphate into DAHP.
primary_references
Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate. | 2020 | DOI 10.1038/s41467-019-14024-1 | PMID 31937786 | https://pubmed.ncbi.nlm.nih.gov/31937786/ | https://doi.org/10.1038/s41467-019-14024-1 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6959354/
primary_references
Publisher correction to metabolic engineering of Escherichia coli for shikimate pathway derivative production | 2020 | DOI 10.1038/s41467-020-14710-5 | https://www.nature.com/articles/s41467-020-14710-5
source_locator
Reviewed reference lines 9-9; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 9–9
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage. · Recorded from source · Recorded from source
**Carbon entry: DAHP formation.** The E. coli pathway map joins phosphoenolpyruvate (PEP) and erythrose-4-phosphate (E4P) through DAHP synthase to form 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP), releasing phosphate. These inputs connect central carbon metabolism to aromatic biosynthesis. The cited engineering study provides pathway and flux-redistribution context; its diagram is not a new kinetic assay for every reaction. Its 2020 publisher correction replaces a duplicated Figure 7 and corrects its legend; the current corrected article is the reference. [Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate.](https://pubmed.ncbi.nlm.nih.gov/31937786/) [Publisher correction to metabolic engineering of Escherichia coli for shikimate pathway derivative production](https://www.nature.com/articles/s41467-020-14710-5)
Complete structured claim and evidence
AroB converts DAHP into 3-dehydroquinate.
3-Deoxy-D-arabino-heptulosonate 7-phosphate / DAHP → 3-Dehydroquinate / DHQ Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
AroB converts DAHP into 3-dehydroquinate.
primary_references
Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate. | 2020 | DOI 10.1038/s41467-019-14024-1 | PMID 31937786 | https://pubmed.ncbi.nlm.nih.gov/31937786/ | https://doi.org/10.1038/s41467-019-14024-1 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6959354/
source_locator
Reviewed reference lines 11-11; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 11–11
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage. · Recorded from source · Recorded from source
**The two steps before shikimate.** E. coli AroB converts DAHP to 3-dehydroquinate (DHQ); AroD dehydrates DHQ to 3-dehydroshikimate (DHS). DHS and shikimate are different metabolites. Separating these intermediates matters when metabolomics shows them accumulating during downstream inhibition. [Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate.](https://pubmed.ncbi.nlm.nih.gov/31937786/)
Complete structured claim and evidence
AroD dehydrates 3-dehydroquinate to 3-dehydroshikimate.
3-Dehydroquinate / DHQ → 3-Dehydroshikimate / DHS Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
AroD dehydrates 3-dehydroquinate to 3-dehydroshikimate.
primary_references
Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate. | 2020 | DOI 10.1038/s41467-019-14024-1 | PMID 31937786 | https://pubmed.ncbi.nlm.nih.gov/31937786/ | https://doi.org/10.1038/s41467-019-14024-1 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6959354/
source_locator
Reviewed reference lines 11-11; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 11–11
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage. · Recorded from source · Recorded from source
**The two steps before shikimate.** E. coli AroB converts DAHP to 3-dehydroquinate (DHQ); AroD dehydrates DHQ to 3-dehydroshikimate (DHS). DHS and shikimate are different metabolites. Separating these intermediates matters when metabolomics shows them accumulating during downstream inhibition. [Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate.](https://pubmed.ncbi.nlm.nih.gov/31937786/)
Complete structured claim and evidence
AroE reduces DHS to shikimate with NADPH oxidation to NADP+.
3-Dehydroshikimate / DHS → Shikimate anion Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted. Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
AroE reduces DHS to shikimate with NADPH oxidation to NADP+.
primary_references
Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate. | 2020 | DOI 10.1038/s41467-019-14024-1 | PMID 31937786 | https://pubmed.ncbi.nlm.nih.gov/31937786/ | https://doi.org/10.1038/s41467-019-14024-1 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6959354/
primary_references
Structures of shikimate dehydrogenase AroE and its Paralog YdiB. A common structural framework for different activities. | 2003 | DOI 10.1074/jbc.m300794200 | PMID 12637497 | https://pubmed.ncbi.nlm.nih.gov/12637497/ | https://doi.org/10.1074/jbc.m300794200
source_locator
Reviewed reference lines 13-13; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 13–13
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage. · Recorded from source · Recorded from source
**NADPH supplies reducing equivalents.** E. coli AroE reduces DHS to shikimate using NADPH, producing NADP+. The reaction is reversible; direction depends on conditions. Primary structural/biochemical work distinguishes NADP-specific AroE from paralog YdiB, which accepts NAD or NADP and has quinate/shikimate dehydrogenase activity. Do not give every homolog identical cofactor specificity or infer that human niacin supplementation necessarily increases gut pathway flux. [Structures of shikimate dehydrogenase AroE and its Paralog YdiB. A common structural framework for different activities.](https://pubmed.ncbi.nlm.nih.gov/12637497/) [Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate.](https://pubmed.ncbi.nlm.nih.gov/31937786/)
Complete structured claim and evidence
NADPH provides reducing equivalents for the biosynthetic AroE reaction.
NADPH → Escherichia coli shikimate dehydrogenase / AroE Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted. Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
E. coli enzyme cofactor specificity.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
NADPH provides reducing equivalents for the biosynthetic AroE reaction.
primary_references
Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate. | 2020 | DOI 10.1038/s41467-019-14024-1 | PMID 31937786 | https://pubmed.ncbi.nlm.nih.gov/31937786/ | https://doi.org/10.1038/s41467-019-14024-1 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6959354/
primary_references
Structures of shikimate dehydrogenase AroE and its Paralog YdiB. A common structural framework for different activities. | 2003 | DOI 10.1074/jbc.m300794200 | PMID 12637497 | https://pubmed.ncbi.nlm.nih.gov/12637497/ | https://doi.org/10.1074/jbc.m300794200
source_locator
Reviewed reference lines 13-13; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 13–13
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli enzyme cofactor specificity. · Recorded from source · Recorded from source
**NADPH supplies reducing equivalents.** E. coli AroE reduces DHS to shikimate using NADPH, producing NADP+. The reaction is reversible; direction depends on conditions. Primary structural/biochemical work distinguishes NADP-specific AroE from paralog YdiB, which accepts NAD or NADP and has quinate/shikimate dehydrogenase activity. Do not give every homolog identical cofactor specificity or infer that human niacin supplementation necessarily increases gut pathway flux. [Structures of shikimate dehydrogenase AroE and its Paralog YdiB. A common structural framework for different activities.](https://pubmed.ncbi.nlm.nih.gov/12637497/) [Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate.](https://pubmed.ncbi.nlm.nih.gov/31937786/)
Complete structured claim and evidence
E. coli YdiB accepts NAD/NADP cofactors for quinate/shikimate dehydrogenase activity.
Escherichia coli quinate/shikimate dehydrogenase / YdiB → NADP+ Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted. Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Primary enzyme specificity/structure comparison.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Paralog-specific acceptance is not a universal AroE property or a fixed in-vivo reaction direction.
plain_language
E. coli YdiB accepts NAD/NADP cofactors for quinate/shikimate dehydrogenase activity.
primary_references
Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate. | 2020 | DOI 10.1038/s41467-019-14024-1 | PMID 31937786 | https://pubmed.ncbi.nlm.nih.gov/31937786/ | https://doi.org/10.1038/s41467-019-14024-1 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6959354/
primary_references
Structures of shikimate dehydrogenase AroE and its Paralog YdiB. A common structural framework for different activities. | 2003 | DOI 10.1074/jbc.m300794200 | PMID 12637497 | https://pubmed.ncbi.nlm.nih.gov/12637497/ | https://doi.org/10.1074/jbc.m300794200
source_locator
Reviewed reference lines 13-13; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 13–13
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Primary enzyme specificity/structure comparison. · Recorded from source · Recorded from source
**NADPH supplies reducing equivalents.** E. coli AroE reduces DHS to shikimate using NADPH, producing NADP+. The reaction is reversible; direction depends on conditions. Primary structural/biochemical work distinguishes NADP-specific AroE from paralog YdiB, which accepts NAD or NADP and has quinate/shikimate dehydrogenase activity. Do not give every homolog identical cofactor specificity or infer that human niacin supplementation necessarily increases gut pathway flux. [Structures of shikimate dehydrogenase AroE and its Paralog YdiB. A common structural framework for different activities.](https://pubmed.ncbi.nlm.nih.gov/12637497/) [Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate.](https://pubmed.ncbi.nlm.nih.gov/31937786/)
Complete structured claim and evidence
The ecoli-arok kinase phosphorylates shikimate using ATP.
Shikimate anion → Shikimate 3-phosphate Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text HTML and indexed abstract reviewed for the stated results; archived locally. Primary publisher article introductory text reviewed; precise affinity estimates are contextual, not newly remeasured.
experimental_model
Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
The ecoli-arok kinase phosphorylates shikimate using ATP.
primary_references
Biochemical and X-ray crystallographic studies on shikimate kinase: the important structural role of the P-loop lysine. | 2001 | DOI 10.1110/ps.52501 | PMID 11369852 | https://pubmed.ncbi.nlm.nih.gov/11369852/ | https://doi.org/10.1110/ps.52501 | https://pmc.ncbi.nlm.nih.gov/articles/PMC2374015/
primary_references
Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers sensitivity to mecillinam. | 2002 | DOI 10.1002/prot.10099 | PMID 12001235 | https://pubmed.ncbi.nlm.nih.gov/12001235/ | https://doi.org/10.1002/prot.10099
source_locator
Reviewed reference lines 15-15; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 15–15
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage. · Recorded from source · Recorded from source
**ATP and magnesium at shikimate kinase.** Shikimate kinase transfers a phosphoryl group from ATP to shikimate, yielding shikimate-3-phosphate and ADP. The Erwinia chrysanthemi enzyme study identifies magnesium dependence and a Mg–ADP structural complex; this is a microbial enzyme requirement, not a demonstrated human magnesium-deficiency phenotype. E. coli has AroK and AroL kinase isoenzymes with different substrate affinities. The AroK structural paper discusses approximate shikimate Km values of 20 mM versus 0.2 mM for the two systems; these are organism/assay properties, not plasma targets. Loss of both kinases produces aromatic-amino-acid auxotrophy; environmental nutrient rescue and isoenzyme compensation matter. [Biochemical and X-ray crystallographic studies on shikimate kinase: the important structural role of the P-loop lysine.](https://pubmed.ncbi.nlm.nih.gov/11369852/) [Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers sensitivity to mecillinam.](https://pubmed.ncbi.nlm.nih.gov/12001235/)
Complete structured claim and evidence
The ecoli-arol kinase phosphorylates shikimate using ATP.
Shikimate anion → Shikimate 3-phosphate Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text HTML and indexed abstract reviewed for the stated results; archived locally. Primary publisher article introductory text reviewed; precise affinity estimates are contextual, not newly remeasured.
experimental_model
Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
The ecoli-arol kinase phosphorylates shikimate using ATP.
primary_references
Biochemical and X-ray crystallographic studies on shikimate kinase: the important structural role of the P-loop lysine. | 2001 | DOI 10.1110/ps.52501 | PMID 11369852 | https://pubmed.ncbi.nlm.nih.gov/11369852/ | https://doi.org/10.1110/ps.52501 | https://pmc.ncbi.nlm.nih.gov/articles/PMC2374015/
primary_references
Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers sensitivity to mecillinam. | 2002 | DOI 10.1002/prot.10099 | PMID 12001235 | https://pubmed.ncbi.nlm.nih.gov/12001235/ | https://doi.org/10.1002/prot.10099
source_locator
Reviewed reference lines 15-15; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 15–15
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage. · Recorded from source · Recorded from source
**ATP and magnesium at shikimate kinase.** Shikimate kinase transfers a phosphoryl group from ATP to shikimate, yielding shikimate-3-phosphate and ADP. The Erwinia chrysanthemi enzyme study identifies magnesium dependence and a Mg–ADP structural complex; this is a microbial enzyme requirement, not a demonstrated human magnesium-deficiency phenotype. E. coli has AroK and AroL kinase isoenzymes with different substrate affinities. The AroK structural paper discusses approximate shikimate Km values of 20 mM versus 0.2 mM for the two systems; these are organism/assay properties, not plasma targets. Loss of both kinases produces aromatic-amino-acid auxotrophy; environmental nutrient rescue and isoenzyme compensation matter. [Biochemical and X-ray crystallographic studies on shikimate kinase: the important structural role of the P-loop lysine.](https://pubmed.ncbi.nlm.nih.gov/11369852/) [Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers sensitivity to mecillinam.](https://pubmed.ncbi.nlm.nih.gov/12001235/)
Complete structured claim and evidence
The studied Erwinia shikimate kinase requires magnesium for its ATP-dependent reaction.
Mg2+ → Erwinia chrysanthemi shikimate kinase Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text HTML and indexed abstract reviewed for the stated results; archived locally. Primary publisher article introductory text reviewed; precise affinity estimates are contextual, not newly remeasured.
experimental_model
Purified Erwinia chrysanthemi enzyme and Mg–ADP structure.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
No human magnesium dose threshold or E. coli-specific quantitative affinity inferred.
plain_language
The studied Erwinia shikimate kinase requires magnesium for its ATP-dependent reaction.
primary_references
Biochemical and X-ray crystallographic studies on shikimate kinase: the important structural role of the P-loop lysine. | 2001 | DOI 10.1110/ps.52501 | PMID 11369852 | https://pubmed.ncbi.nlm.nih.gov/11369852/ | https://doi.org/10.1110/ps.52501 | https://pmc.ncbi.nlm.nih.gov/articles/PMC2374015/
primary_references
Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers sensitivity to mecillinam. | 2002 | DOI 10.1002/prot.10099 | PMID 12001235 | https://pubmed.ncbi.nlm.nih.gov/12001235/ | https://doi.org/10.1002/prot.10099
source_locator
Reviewed reference lines 15-15; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 15–15
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Purified Erwinia chrysanthemi enzyme and Mg–ADP structure. · Recorded from source · Recorded from source
**ATP and magnesium at shikimate kinase.** Shikimate kinase transfers a phosphoryl group from ATP to shikimate, yielding shikimate-3-phosphate and ADP. The Erwinia chrysanthemi enzyme study identifies magnesium dependence and a Mg–ADP structural complex; this is a microbial enzyme requirement, not a demonstrated human magnesium-deficiency phenotype. E. coli has AroK and AroL kinase isoenzymes with different substrate affinities. The AroK structural paper discusses approximate shikimate Km values of 20 mM versus 0.2 mM for the two systems; these are organism/assay properties, not plasma targets. Loss of both kinases produces aromatic-amino-acid auxotrophy; environmental nutrient rescue and isoenzyme compensation matter. [Biochemical and X-ray crystallographic studies on shikimate kinase: the important structural role of the P-loop lysine.](https://pubmed.ncbi.nlm.nih.gov/11369852/) [Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers sensitivity to mecillinam.](https://pubmed.ncbi.nlm.nih.gov/12001235/)
Complete structured claim and evidence
Loss of both AroK and AroL produces aromatic-amino-acid auxotrophy in E. coli.
Escherichia coli shikimate kinase I / AroK → E. coli growth dependent on external aromatic amino acids Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full-text HTML and indexed abstract reviewed for the stated results; archived locally. Primary publisher article introductory text reviewed; precise affinity estimates are contextual, not newly remeasured.
experimental_condition
Functional shikimate kinase background lost · Escherichia coli shikimate kinase I / AroK Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
Functional shikimate kinase background lost · Escherichia coli shikimate kinase II / AroL Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "Both AroK and AroL unavailable", "comparator": "Functional shikimate kinase background", "endpoint": "Loss of both AroK and AroL produces aromatic-amino-acid auxotrophy in E. coli.", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "ecoli-arok", "state": "lost"}, {"entity_slug": "ecoli-arol", "state": "lost"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
E. coli double-kinase loss phenotype discussed in the primary structural study.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
Loss of both AroK and AroL produces aromatic-amino-acid auxotrophy in E. coli.
primary_references
Biochemical and X-ray crystallographic studies on shikimate kinase: the important structural role of the P-loop lysine. | 2001 | DOI 10.1110/ps.52501 | PMID 11369852 | https://pubmed.ncbi.nlm.nih.gov/11369852/ | https://doi.org/10.1110/ps.52501 | https://pmc.ncbi.nlm.nih.gov/articles/PMC2374015/
primary_references
Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers sensitivity to mecillinam. | 2002 | DOI 10.1002/prot.10099 | PMID 12001235 | https://pubmed.ncbi.nlm.nih.gov/12001235/ | https://doi.org/10.1002/prot.10099
source_locator
Reviewed reference lines 15-15; exact primary location described in quoted passage where extracted.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 15–15
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli double-kinase loss phenotype discussed in the primary structural study. · Recorded from source · Recorded from source
**ATP and magnesium at shikimate kinase.** Shikimate kinase transfers a phosphoryl group from ATP to shikimate, yielding shikimate-3-phosphate and ADP. The Erwinia chrysanthemi enzyme study identifies magnesium dependence and a Mg–ADP structural complex; this is a microbial enzyme requirement, not a demonstrated human magnesium-deficiency phenotype. E. coli has AroK and AroL kinase isoenzymes with different substrate affinities. The AroK structural paper discusses approximate shikimate Km values of 20 mM versus 0.2 mM for the two systems; these are organism/assay properties, not plasma targets. Loss of both kinases produces aromatic-amino-acid auxotrophy; environmental nutrient rescue and isoenzyme compensation matter. [Biochemical and X-ray crystallographic studies on shikimate kinase: the important structural role of the P-loop lysine.](https://pubmed.ncbi.nlm.nih.gov/11369852/) [Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers sensitivity to mecillinam.](https://pubmed.ncbi.nlm.nih.gov/12001235/)
Complete structured claim and evidence
EPSPS uses PEP and shikimate-3-phosphate to produce EPSP and phosphate.
Shikimate 3-phosphate → 5-Enolpyruvylshikimate 3-phosphate / EPSP Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text HTML and indexed abstract reviewed for the stated results; archived locally.
experimental_model
Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
EPSPS uses PEP and shikimate-3-phosphate to produce EPSP and phosphate.
primary_references
Molecular basis for the herbicide resistance of Roundup Ready crops. | 2006 | DOI 10.1073/pnas.0603638103 | PMID 16916934 | https://pubmed.ncbi.nlm.nih.gov/16916934/ | https://doi.org/10.1073/pnas.0603638103 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1559744/
source_locator
Reviewed reference lines 17-17; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 17–17
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage. · Recorded from source · Recorded from source
**EPSPS uses a second PEP molecule.** E. coli EPSPS (AroA) transfers an enolpyruvyl group from a second PEP molecule to shikimate-3-phosphate, making 5-enolpyruvylshikimate-3-phosphate (EPSP) and phosphate. Glyphosate inhibits this enzyme by occupying the PEP-associated substrate site in the substrate-bound enzyme. Purified-enzyme IC50 estimates were about 2.5 µM for E. coli EPSPS and 11 mM for CP4 EPSPS. These are not interchangeable microbial-growth thresholds or human intestinal effect concentrations. Adding shikimate upstream does not remove the need for EPSPS downstream. [Molecular basis for the herbicide resistance of Roundup Ready crops.](https://pubmed.ncbi.nlm.nih.gov/16916934/)
Complete structured claim and evidence
Glyphosate inhibited ecoli-aroa with an approximate purified-enzyme IC50 of 2.5 micromolar.
Glyphosate → Escherichia coli EPSP synthase / AroA Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text HTML and indexed abstract reviewed for the stated results; archived locally.
experimental_contrast
{"intervention": "Glyphosate titration", "comparator": "Enzyme without glyphosate", "endpoint": "Glyphosate inhibited ecoli-aroa with an approximate purified-enzyme IC50 of 2.5 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Purified enzyme comparison, Funke 2006.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
IC50 depends on assay conditions; not a growth threshold, dietary exposure limit or complete microbiome response.
plain_language
Glyphosate inhibited ecoli-aroa with an approximate purified-enzyme IC50 of 2.5 micromolar.
primary_references
Molecular basis for the herbicide resistance of Roundup Ready crops. | 2006 | DOI 10.1073/pnas.0603638103 | PMID 16916934 | https://pubmed.ncbi.nlm.nih.gov/16916934/ | https://doi.org/10.1073/pnas.0603638103 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1559744/
source_locator
Reviewed reference lines 17-17; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 17–17
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Purified enzyme comparison, Funke 2006. · Recorded from source · Recorded from source
**EPSPS uses a second PEP molecule.** E. coli EPSPS (AroA) transfers an enolpyruvyl group from a second PEP molecule to shikimate-3-phosphate, making 5-enolpyruvylshikimate-3-phosphate (EPSP) and phosphate. Glyphosate inhibits this enzyme by occupying the PEP-associated substrate site in the substrate-bound enzyme. Purified-enzyme IC50 estimates were about 2.5 µM for E. coli EPSPS and 11 mM for CP4 EPSPS. These are not interchangeable microbial-growth thresholds or human intestinal effect concentrations. Adding shikimate upstream does not remove the need for EPSPS downstream. [Molecular basis for the herbicide resistance of Roundup Ready crops.](https://pubmed.ncbi.nlm.nih.gov/16916934/)
Complete structured claim and evidence
Glyphosate inhibited cp4-epsps with an approximate purified-enzyme IC50 of 11 millimolar.
Glyphosate → Agrobacterium strain CP4 EPSP synthase Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text HTML and indexed abstract reviewed for the stated results; archived locally.
experimental_contrast
{"intervention": "Glyphosate titration", "comparator": "Enzyme without glyphosate", "endpoint": "Glyphosate inhibited cp4-epsps with an approximate purified-enzyme IC50 of 11 millimolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Purified enzyme comparison, Funke 2006.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
IC50 depends on assay conditions; not a growth threshold, dietary exposure limit or complete microbiome response.
plain_language
Glyphosate inhibited cp4-epsps with an approximate purified-enzyme IC50 of 11 millimolar.
primary_references
Molecular basis for the herbicide resistance of Roundup Ready crops. | 2006 | DOI 10.1073/pnas.0603638103 | PMID 16916934 | https://pubmed.ncbi.nlm.nih.gov/16916934/ | https://doi.org/10.1073/pnas.0603638103 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1559744/
source_locator
Reviewed reference lines 17-17; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 17–17
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Purified enzyme comparison, Funke 2006. · Recorded from source · Recorded from source
**EPSPS uses a second PEP molecule.** E. coli EPSPS (AroA) transfers an enolpyruvyl group from a second PEP molecule to shikimate-3-phosphate, making 5-enolpyruvylshikimate-3-phosphate (EPSP) and phosphate. Glyphosate inhibits this enzyme by occupying the PEP-associated substrate site in the substrate-bound enzyme. Purified-enzyme IC50 estimates were about 2.5 µM for E. coli EPSPS and 11 mM for CP4 EPSPS. These are not interchangeable microbial-growth thresholds or human intestinal effect concentrations. Adding shikimate upstream does not remove the need for EPSPS downstream. [Molecular basis for the herbicide resistance of Roundup Ready crops.](https://pubmed.ncbi.nlm.nih.gov/16916934/)
Complete structured claim and evidence
Potassium activated purified CP4 EPSPS, with a reported binding estimate around 25 mM.
Potassium ion → Agrobacterium strain CP4 EPSP synthase Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text HTML and indexed abstract reviewed for the stated results; archived locally.
experimental_contrast
{"intervention": "K+ supplied in enzyme assay", "comparator": "Assay without activating monovalent cation", "endpoint": "Potassium activated purified CP4 EPSPS, with a reported binding estimate around 25 mM.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Purified strain CP4 enzyme; monovalent-cation comparison.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Specific bacterial enzyme, not human potassium status or a universal EPSPS gate.
plain_language
Potassium activated purified CP4 EPSPS, with a reported binding estimate around 25 mM.
primary_references
Molecular basis for the herbicide resistance of Roundup Ready crops. | 2006 | DOI 10.1073/pnas.0603638103 | PMID 16916934 | https://pubmed.ncbi.nlm.nih.gov/16916934/ | https://doi.org/10.1073/pnas.0603638103 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1559744/
source_locator
Reviewed reference lines 19-19; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 19–19
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Purified strain CP4 enzyme; monovalent-cation comparison. · Recorded from source · Recorded from source
**Potassium dependence is enzyme-specific.** The CP4 EPSPS study found activation by K+, NH4+ and Rb+; the reported K+ dissociation estimate was approximately 25 mM. This result belongs to that purified bacterial enzyme. It does not mean human potassium intake controls all EPSPS enzymes or makes glyphosate inhibition irrelevant. [Molecular basis for the herbicide resistance of Roundup Ready crops.](https://pubmed.ncbi.nlm.nih.gov/16916934/)
Complete structured claim and evidence
AroC forms chorismate from EPSP with reduced-FMN dependence and phosphate elimination.
5-Enolpyruvylshikimate 3-phosphate / EPSP → Chorismate Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
AroC forms chorismate from EPSP with reduced-FMN dependence and phosphate elimination.
primary_references
Evidence for a major structural change in Escherichia coli chorismate synthase induced by flavin and substrate binding. | 1998 | DOI 10.1042/bj3350319 | PMID 9761730 | https://pubmed.ncbi.nlm.nih.gov/9761730/ | https://doi.org/10.1042/bj3350319 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1219785/
primary_references
Mechanism of chorismate synthase. Role of the two invariant histidine residues in the active site. | 2004 | DOI 10.1074/jbc.m312471200 | PMID 14668332 | https://pubmed.ncbi.nlm.nih.gov/14668332/ | https://doi.org/10.1074/jbc.m312471200
source_locator
Reviewed reference lines 21-21; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 21–21
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage. · Recorded from source · Recorded from source
**Chorismate synthase needs reduced FMN.** E. coli AroC converts EPSP to chorismate with phosphate elimination. Reduced FMN is required although the overall substrate conversion is not a net redox reaction; flavin is a catalytic cofactor rather than a stoichiometrically consumed vitamin. The 1998 study observed a stable oxidized-FMN/EPSP/enzyme complex without productive turnover. Binding, cofactor quantity and cofactor redox state therefore answer different questions. In Neurospora crassa, bifunctional chorismate synthase can use NADPH to reduce its flavin; that reductase capability must not be assigned to every bacterial AroC. [Evidence for a major structural change in Escherichia coli chorismate synthase induced by flavin and substrate binding.](https://pubmed.ncbi.nlm.nih.gov/9761730/) [Mechanism of chorismate synthase. Role of the two invariant histidine residues in the active site.](https://pubmed.ncbi.nlm.nih.gov/14668332/)
Complete structured claim and evidence
Reduced FMN supports productive E. coli chorismate-synthase catalysis.
Reduced flavin mononucleotide / FMNH2 → Escherichia coli chorismate synthase / AroC Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Purified E. coli chorismate synthase.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Catalytic redox-state requirement; no net stoichiometric consumption of FMN, dietary B2 deficiency or human phenotype inferred.
plain_language
Reduced FMN supports productive E. coli chorismate-synthase catalysis.
primary_references
Evidence for a major structural change in Escherichia coli chorismate synthase induced by flavin and substrate binding. | 1998 | DOI 10.1042/bj3350319 | PMID 9761730 | https://pubmed.ncbi.nlm.nih.gov/9761730/ | https://doi.org/10.1042/bj3350319 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1219785/
primary_references
Mechanism of chorismate synthase. Role of the two invariant histidine residues in the active site. | 2004 | DOI 10.1074/jbc.m312471200 | PMID 14668332 | https://pubmed.ncbi.nlm.nih.gov/14668332/ | https://doi.org/10.1074/jbc.m312471200
source_locator
Reviewed reference lines 21-21; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 21–21
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Purified E. coli chorismate synthase. · Recorded from source · Recorded from source
**Chorismate synthase needs reduced FMN.** E. coli AroC converts EPSP to chorismate with phosphate elimination. Reduced FMN is required although the overall substrate conversion is not a net redox reaction; flavin is a catalytic cofactor rather than a stoichiometrically consumed vitamin. The 1998 study observed a stable oxidized-FMN/EPSP/enzyme complex without productive turnover. Binding, cofactor quantity and cofactor redox state therefore answer different questions. In Neurospora crassa, bifunctional chorismate synthase can use NADPH to reduce its flavin; that reductase capability must not be assigned to every bacterial AroC. [Evidence for a major structural change in Escherichia coli chorismate synthase induced by flavin and substrate binding.](https://pubmed.ncbi.nlm.nih.gov/9761730/) [Mechanism of chorismate synthase. Role of the two invariant histidine residues in the active site.](https://pubmed.ncbi.nlm.nih.gov/14668332/)
Complete structured claim and evidence
An oxidized-FMN/EPSP/enzyme complex formed without productive chorismate-synthase turnover.
Flavin mononucleotide → Escherichia coli chorismate synthase / AroC Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
E. coli ternary-complex experiment.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Null denotes no productive turnover in the oxidized complex, not equal activity versus reduced FMN; binding and catalysis are distinct.
plain_language
An oxidized-FMN/EPSP/enzyme complex formed without productive chorismate-synthase turnover.
primary_references
Evidence for a major structural change in Escherichia coli chorismate synthase induced by flavin and substrate binding. | 1998 | DOI 10.1042/bj3350319 | PMID 9761730 | https://pubmed.ncbi.nlm.nih.gov/9761730/ | https://doi.org/10.1042/bj3350319 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1219785/
primary_references
Mechanism of chorismate synthase. Role of the two invariant histidine residues in the active site. | 2004 | DOI 10.1074/jbc.m312471200 | PMID 14668332 | https://pubmed.ncbi.nlm.nih.gov/14668332/ | https://doi.org/10.1074/jbc.m312471200
source_locator
Reviewed reference lines 21-21; exact primary location described in quoted passage where extracted.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 21–21
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli ternary-complex experiment. · Recorded from source · Recorded from source
**Chorismate synthase needs reduced FMN.** E. coli AroC converts EPSP to chorismate with phosphate elimination. Reduced FMN is required although the overall substrate conversion is not a net redox reaction; flavin is a catalytic cofactor rather than a stoichiometrically consumed vitamin. The 1998 study observed a stable oxidized-FMN/EPSP/enzyme complex without productive turnover. Binding, cofactor quantity and cofactor redox state therefore answer different questions. In Neurospora crassa, bifunctional chorismate synthase can use NADPH to reduce its flavin; that reductase capability must not be assigned to every bacterial AroC. [Evidence for a major structural change in Escherichia coli chorismate synthase induced by flavin and substrate binding.](https://pubmed.ncbi.nlm.nih.gov/9761730/) [Mechanism of chorismate synthase. Role of the two invariant histidine residues in the active site.](https://pubmed.ncbi.nlm.nih.gov/14668332/)
Complete structured claim and evidence
Neurospora crassa bifunctional chorismate synthase can reduce FMN using NADPH.
Flavin mononucleotide → Reduced flavin mononucleotide / FMNH2 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Purified fungal bifunctional chorismate synthase, not all bacterial enzymes.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
Neurospora crassa bifunctional chorismate synthase can reduce FMN using NADPH.
primary_references
Evidence for a major structural change in Escherichia coli chorismate synthase induced by flavin and substrate binding. | 1998 | DOI 10.1042/bj3350319 | PMID 9761730 | https://pubmed.ncbi.nlm.nih.gov/9761730/ | https://doi.org/10.1042/bj3350319 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1219785/
primary_references
Mechanism of chorismate synthase. Role of the two invariant histidine residues in the active site. | 2004 | DOI 10.1074/jbc.m312471200 | PMID 14668332 | https://pubmed.ncbi.nlm.nih.gov/14668332/ | https://doi.org/10.1074/jbc.m312471200
source_locator
Reviewed reference lines 21-21; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 21–21
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Purified fungal bifunctional chorismate synthase, not all bacterial enzymes. · Recorded from source · Recorded from source
**Chorismate synthase needs reduced FMN.** E. coli AroC converts EPSP to chorismate with phosphate elimination. Reduced FMN is required although the overall substrate conversion is not a net redox reaction; flavin is a catalytic cofactor rather than a stoichiometrically consumed vitamin. The 1998 study observed a stable oxidized-FMN/EPSP/enzyme complex without productive turnover. Binding, cofactor quantity and cofactor redox state therefore answer different questions. In Neurospora crassa, bifunctional chorismate synthase can use NADPH to reduce its flavin; that reductase capability must not be assigned to every bacterial AroC. [Evidence for a major structural change in Escherichia coli chorismate synthase induced by flavin and substrate binding.](https://pubmed.ncbi.nlm.nih.gov/9761730/) [Mechanism of chorismate synthase. Role of the two invariant histidine residues in the active site.](https://pubmed.ncbi.nlm.nih.gov/14668332/)
Complete structured claim and evidence
Chorismate supplies a multistep E. coli biosynthetic branch toward l-phenylalanine.
Chorismate → L-Phenylalanine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
E. coli pathway map/engineering context.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Multistep precursor relationship; not one reaction, direct conversion by humans, or measured host nutrient delivery.
plain_language
Chorismate supplies a multistep E. coli biosynthetic branch toward l-phenylalanine.
primary_references
Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate. | 2020 | DOI 10.1038/s41467-019-14024-1 | PMID 31937786 | https://pubmed.ncbi.nlm.nih.gov/31937786/ | https://doi.org/10.1038/s41467-019-14024-1 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6959354/
source_locator
Reviewed reference lines 23-23; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 23–23
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli pathway map/engineering context. · Recorded from source · Recorded from source
**Aromatic amino acids and competing branches.** Chorismate feeds organism-dependent synthesis of phenylalanine, tyrosine and tryptophan. The E. coli engineering study shows that central carbon supply and competing reactions can redistribute product yields; it does not measure host nutrient delivery. Humans obtain essential phenylalanine and tryptophan through nutrition and can convert phenylalanine to tyrosine through a different pathway. Bacterial synthesis, extracellular release, community use and human absorption are separate stages. Chorismate also participates in specialized siderophore pathways in some organisms, but no universal increase in iron delivery follows from having more precursor. [Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate.](https://pubmed.ncbi.nlm.nih.gov/31937786/)
Complete structured claim and evidence
Chorismate supplies a multistep E. coli biosynthetic branch toward l-tyrosine.
Chorismate → L-Tyrosine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
E. coli pathway map/engineering context.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Multistep precursor relationship; not one reaction, direct conversion by humans, or measured host nutrient delivery.
plain_language
Chorismate supplies a multistep E. coli biosynthetic branch toward l-tyrosine.
primary_references
Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate. | 2020 | DOI 10.1038/s41467-019-14024-1 | PMID 31937786 | https://pubmed.ncbi.nlm.nih.gov/31937786/ | https://doi.org/10.1038/s41467-019-14024-1 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6959354/
source_locator
Reviewed reference lines 23-23; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 23–23
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli pathway map/engineering context. · Recorded from source · Recorded from source
**Aromatic amino acids and competing branches.** Chorismate feeds organism-dependent synthesis of phenylalanine, tyrosine and tryptophan. The E. coli engineering study shows that central carbon supply and competing reactions can redistribute product yields; it does not measure host nutrient delivery. Humans obtain essential phenylalanine and tryptophan through nutrition and can convert phenylalanine to tyrosine through a different pathway. Bacterial synthesis, extracellular release, community use and human absorption are separate stages. Chorismate also participates in specialized siderophore pathways in some organisms, but no universal increase in iron delivery follows from having more precursor. [Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate.](https://pubmed.ncbi.nlm.nih.gov/31937786/)
Complete structured claim and evidence
Chorismate supplies a multistep E. coli biosynthetic branch toward l-tryptophan.
Chorismate → L-Tryptophan Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
E. coli pathway map/engineering context.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Multistep precursor relationship; not one reaction, direct conversion by humans, or measured host nutrient delivery.
plain_language
Chorismate supplies a multistep E. coli biosynthetic branch toward l-tryptophan.
primary_references
Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate. | 2020 | DOI 10.1038/s41467-019-14024-1 | PMID 31937786 | https://pubmed.ncbi.nlm.nih.gov/31937786/ | https://doi.org/10.1038/s41467-019-14024-1 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6959354/
source_locator
Reviewed reference lines 23-23; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 23–23
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli pathway map/engineering context. · Recorded from source · Recorded from source
**Aromatic amino acids and competing branches.** Chorismate feeds organism-dependent synthesis of phenylalanine, tyrosine and tryptophan. The E. coli engineering study shows that central carbon supply and competing reactions can redistribute product yields; it does not measure host nutrient delivery. Humans obtain essential phenylalanine and tryptophan through nutrition and can convert phenylalanine to tyrosine through a different pathway. Bacterial synthesis, extracellular release, community use and human absorption are separate stages. Chorismate also participates in specialized siderophore pathways in some organisms, but no universal increase in iron delivery follows from having more precursor. [Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate.](https://pubmed.ncbi.nlm.nih.gov/31937786/)
Complete structured claim and evidence
PabA supplies glutamine nitrogen for the PabB aminodeoxychorismate reaction.
L-Glutamine → L-Glutamate Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
E. coli PabA/PabB coupled enzyme system; nitrogen transfer is coupled, not an independent folate concentration effect.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
PabA supplies glutamine nitrogen for the PabB aminodeoxychorismate reaction.
primary_references
Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme. | 1992 | DOI 10.1128/jb.174.16.5317-5323.1992 | PMID 1644759 | https://pubmed.ncbi.nlm.nih.gov/1644759/ | https://doi.org/10.1128/jb.174.16.5317-5323.1992 | https://pmc.ncbi.nlm.nih.gov/articles/PMC206368/
primary_references
para-aminobenzoate synthesis from chorismate occurs in two steps. | 1989 | DOI 10.1016/s0021-9258(18)81833-6 | PMID 2656685 | https://pubmed.ncbi.nlm.nih.gov/2656685/ | https://doi.org/10.1016/s0021-9258(18)81833-6
source_locator
Reviewed reference lines 25-25; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 25–25
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli PabA/PabB coupled enzyme system; nitrogen transfer is coupled, not an independent folate concentration effect. · Recorded from source · Recorded from source
**The folate branch contains a B6-dependent step.** In E. coli, PabA supplies nitrogen from glutamine, generating glutamate; PabB uses chorismate and that nitrogen to form 4-amino-4-deoxychorismate. PabC then cleaves this intermediate to p-aminobenzoate (pABA) and pyruvate. The purified PabC enzyme contains pyridoxal phosphate (PLP), a B6 cofactor. A disrupted pabC strain required external pABA for growth. This establishes a microbial cofactor and biosynthetic dependency, not that marginal human B6 deficiency causes microbial folate failure. pABA is a precursor used in bacterial folate synthesis, not folate itself. [para-aminobenzoate synthesis from chorismate occurs in two steps.](https://pubmed.ncbi.nlm.nih.gov/2656685/) [Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme.](https://pubmed.ncbi.nlm.nih.gov/1644759/)
Complete structured claim and evidence
PabB forms aminodeoxychorismate using nitrogen supplied by the glutamine/PabA system.
Chorismate → 4-Amino-4-deoxychorismate Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
PabB forms aminodeoxychorismate using nitrogen supplied by the glutamine/PabA system.
primary_references
Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme. | 1992 | DOI 10.1128/jb.174.16.5317-5323.1992 | PMID 1644759 | https://pubmed.ncbi.nlm.nih.gov/1644759/ | https://doi.org/10.1128/jb.174.16.5317-5323.1992 | https://pmc.ncbi.nlm.nih.gov/articles/PMC206368/
primary_references
para-aminobenzoate synthesis from chorismate occurs in two steps. | 1989 | DOI 10.1016/s0021-9258(18)81833-6 | PMID 2656685 | https://pubmed.ncbi.nlm.nih.gov/2656685/ | https://doi.org/10.1016/s0021-9258(18)81833-6
source_locator
Reviewed reference lines 25-25; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 25–25
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage. · Recorded from source · Recorded from source
**The folate branch contains a B6-dependent step.** In E. coli, PabA supplies nitrogen from glutamine, generating glutamate; PabB uses chorismate and that nitrogen to form 4-amino-4-deoxychorismate. PabC then cleaves this intermediate to p-aminobenzoate (pABA) and pyruvate. The purified PabC enzyme contains pyridoxal phosphate (PLP), a B6 cofactor. A disrupted pabC strain required external pABA for growth. This establishes a microbial cofactor and biosynthetic dependency, not that marginal human B6 deficiency causes microbial folate failure. pABA is a precursor used in bacterial folate synthesis, not folate itself. [para-aminobenzoate synthesis from chorismate occurs in two steps.](https://pubmed.ncbi.nlm.nih.gov/2656685/) [Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme.](https://pubmed.ncbi.nlm.nih.gov/1644759/)
Complete structured claim and evidence
PLP-containing PabC cleaves aminodeoxychorismate to pABA and pyruvate.
4-Amino-4-deoxychorismate → 4-Aminobenzoate / pABA Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
PLP-containing PabC cleaves aminodeoxychorismate to pABA and pyruvate.
primary_references
Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme. | 1992 | DOI 10.1128/jb.174.16.5317-5323.1992 | PMID 1644759 | https://pubmed.ncbi.nlm.nih.gov/1644759/ | https://doi.org/10.1128/jb.174.16.5317-5323.1992 | https://pmc.ncbi.nlm.nih.gov/articles/PMC206368/
primary_references
para-aminobenzoate synthesis from chorismate occurs in two steps. | 1989 | DOI 10.1016/s0021-9258(18)81833-6 | PMID 2656685 | https://pubmed.ncbi.nlm.nih.gov/2656685/ | https://doi.org/10.1016/s0021-9258(18)81833-6
source_locator
Reviewed reference lines 25-25; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 25–25
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage. · Recorded from source · Recorded from source
**The folate branch contains a B6-dependent step.** In E. coli, PabA supplies nitrogen from glutamine, generating glutamate; PabB uses chorismate and that nitrogen to form 4-amino-4-deoxychorismate. PabC then cleaves this intermediate to p-aminobenzoate (pABA) and pyruvate. The purified PabC enzyme contains pyridoxal phosphate (PLP), a B6 cofactor. A disrupted pabC strain required external pABA for growth. This establishes a microbial cofactor and biosynthetic dependency, not that marginal human B6 deficiency causes microbial folate failure. pABA is a precursor used in bacterial folate synthesis, not folate itself. [para-aminobenzoate synthesis from chorismate occurs in two steps.](https://pubmed.ncbi.nlm.nih.gov/2656685/) [Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme.](https://pubmed.ncbi.nlm.nih.gov/1644759/)
Complete structured claim and evidence
Purified E. coli PabC contains PLP as its enzyme cofactor.
PLP → Escherichia coli aminodeoxychorismate lyase / PabC Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Purified bacterial aminodeoxychorismate lyase.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
Purified E. coli PabC contains PLP as its enzyme cofactor.
primary_references
Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme. | 1992 | DOI 10.1128/jb.174.16.5317-5323.1992 | PMID 1644759 | https://pubmed.ncbi.nlm.nih.gov/1644759/ | https://doi.org/10.1128/jb.174.16.5317-5323.1992 | https://pmc.ncbi.nlm.nih.gov/articles/PMC206368/
primary_references
para-aminobenzoate synthesis from chorismate occurs in two steps. | 1989 | DOI 10.1016/s0021-9258(18)81833-6 | PMID 2656685 | https://pubmed.ncbi.nlm.nih.gov/2656685/ | https://doi.org/10.1016/s0021-9258(18)81833-6
source_locator
Reviewed reference lines 25-25; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 25–25
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Purified bacterial aminodeoxychorismate lyase. · Recorded from source · Recorded from source
**The folate branch contains a B6-dependent step.** In E. coli, PabA supplies nitrogen from glutamine, generating glutamate; PabB uses chorismate and that nitrogen to form 4-amino-4-deoxychorismate. PabC then cleaves this intermediate to p-aminobenzoate (pABA) and pyruvate. The purified PabC enzyme contains pyridoxal phosphate (PLP), a B6 cofactor. A disrupted pabC strain required external pABA for growth. This establishes a microbial cofactor and biosynthetic dependency, not that marginal human B6 deficiency causes microbial folate failure. pABA is a precursor used in bacterial folate synthesis, not folate itself. [para-aminobenzoate synthesis from chorismate occurs in two steps.](https://pubmed.ncbi.nlm.nih.gov/2656685/) [Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme.](https://pubmed.ncbi.nlm.nih.gov/1644759/)
Complete structured claim and evidence
External pABA supports growth of the disrupted-pabC strain.
4-Aminobenzoate / pABA → Growth of PabC-deficient E. coli Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_condition
Same disrupted-pabC strain without external pABA disrupted · Escherichia coli aminodeoxychorismate lyase / PabC Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
Same disrupted-pabC strain without external pABA supplied · 4-Aminobenzoate / pABA Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "External pABA in disrupted-pabC background", "comparator": "Same disrupted-pabC strain without external pABA", "endpoint": "External pABA supports growth of the disrupted-pabC strain.", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "ecoli-pabc", "state": "disrupted"}, {"entity_slug": "4-aminobenzoate", "state": "supplied"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
E. coli genetic machinery impairment and nutritional rescue.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
External pABA supports growth of the disrupted-pabC strain.
primary_references
Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme. | 1992 | DOI 10.1128/jb.174.16.5317-5323.1992 | PMID 1644759 | https://pubmed.ncbi.nlm.nih.gov/1644759/ | https://doi.org/10.1128/jb.174.16.5317-5323.1992 | https://pmc.ncbi.nlm.nih.gov/articles/PMC206368/
primary_references
para-aminobenzoate synthesis from chorismate occurs in two steps. | 1989 | DOI 10.1016/s0021-9258(18)81833-6 | PMID 2656685 | https://pubmed.ncbi.nlm.nih.gov/2656685/ | https://doi.org/10.1016/s0021-9258(18)81833-6
source_locator
Reviewed reference lines 25-25; exact primary location described in quoted passage where extracted.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 25–25
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli genetic machinery impairment and nutritional rescue. · Recorded from source · Recorded from source
**The folate branch contains a B6-dependent step.** In E. coli, PabA supplies nitrogen from glutamine, generating glutamate; PabB uses chorismate and that nitrogen to form 4-amino-4-deoxychorismate. PabC then cleaves this intermediate to p-aminobenzoate (pABA) and pyruvate. The purified PabC enzyme contains pyridoxal phosphate (PLP), a B6 cofactor. A disrupted pabC strain required external pABA for growth. This establishes a microbial cofactor and biosynthetic dependency, not that marginal human B6 deficiency causes microbial folate failure. pABA is a precursor used in bacterial folate synthesis, not folate itself. [para-aminobenzoate synthesis from chorismate occurs in two steps.](https://pubmed.ncbi.nlm.nih.gov/2656685/) [Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme.](https://pubmed.ncbi.nlm.nih.gov/1644759/)
Complete structured claim and evidence
pABA is a bacterial folate biosynthetic precursor downstream of the chorismate/PabC branch.
4-Aminobenzoate / pABA → Folate (vitamin B9) Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
E. coli biosynthesis context, not mammalian de-novo folate synthesis.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Multistep branch relationship; not direct pABA-to-folate conversion, increased human plasma folate or a supplement effect.
plain_language
pABA is a bacterial folate biosynthetic precursor downstream of the chorismate/PabC branch.
primary_references
Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme. | 1992 | DOI 10.1128/jb.174.16.5317-5323.1992 | PMID 1644759 | https://pubmed.ncbi.nlm.nih.gov/1644759/ | https://doi.org/10.1128/jb.174.16.5317-5323.1992 | https://pmc.ncbi.nlm.nih.gov/articles/PMC206368/
primary_references
para-aminobenzoate synthesis from chorismate occurs in two steps. | 1989 | DOI 10.1016/s0021-9258(18)81833-6 | PMID 2656685 | https://pubmed.ncbi.nlm.nih.gov/2656685/ | https://doi.org/10.1016/s0021-9258(18)81833-6
source_locator
Reviewed reference lines 25-25; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 25–25
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli biosynthesis context, not mammalian de-novo folate synthesis. · Recorded from source · Recorded from source
**The folate branch contains a B6-dependent step.** In E. coli, PabA supplies nitrogen from glutamine, generating glutamate; PabB uses chorismate and that nitrogen to form 4-amino-4-deoxychorismate. PabC then cleaves this intermediate to p-aminobenzoate (pABA) and pyruvate. The purified PabC enzyme contains pyridoxal phosphate (PLP), a B6 cofactor. A disrupted pabC strain required external pABA for growth. This establishes a microbial cofactor and biosynthetic dependency, not that marginal human B6 deficiency causes microbial folate failure. pABA is a precursor used in bacterial folate synthesis, not folate itself. [para-aminobenzoate synthesis from chorismate occurs in two steps.](https://pubmed.ncbi.nlm.nih.gov/2656685/) [Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme.](https://pubmed.ncbi.nlm.nih.gov/1644759/)
Complete structured claim and evidence
Isotope-labeled shikimate contributed carbon to E. coli MK-8 in the historical labeling experiment.
Shikimate anion → Menaquinone-8 / MK-8 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
E. coli 1966 isotope tracing; shikimate ring carbon versus methionine methyl carbon.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Carbon incorporation, not complete enzymatic sequence, human MK-7 production or oral vitamin-K efficacy.
plain_language
Isotope-labeled shikimate contributed carbon to E. coli MK-8 in the historical labeling experiment.
primary_references
Biosynthesis of ubiquinone in Escherichia coli K-12: biochemical and genetic characterization of a mutant unable to convert chorismate into 4-hydroxybenzoate. | 1974 | DOI 10.1128/jb.118.1.41-45.1974 | PMID 4595202 | https://pubmed.ncbi.nlm.nih.gov/4595202/ | https://doi.org/10.1128/jb.118.1.41-45.1974 | https://pmc.ncbi.nlm.nih.gov/articles/PMC246637/
primary_references
The role of shikimic acid in the biosynthesis of vitamin K2. | 1966 | DOI 10.1042/bj1000001 | PMID 5337721 | https://pubmed.ncbi.nlm.nih.gov/5337721/ | https://doi.org/10.1042/bj1000001 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1265084/
source_locator
Reviewed reference lines 27-27; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 27–27
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli 1966 isotope tracing; shikimate ring carbon versus methionine methyl carbon. · Recorded from source · Recorded from source
**The K and Q branches are organism-specific.** Isotope experiments in E. coli traced shikimate carbon into the benzene ring of menaquinone-8 (MK-8), and methionine-derived methyl carbon into that product. This does not establish increased human MK-7, vitamin-K function or an oral shikimate dose response. Separately, an E. coli ubiC mutant failed to convert chorismate to 4-hydroxybenzoate and produced little ubiquinone unless supplied with 4-hydroxybenzoate. UbiC therefore identifies a branch-specific supply bottleneck; bacterial ubiquinone production is not synonymous with human mitochondrial CoQ10 synthesis. [The role of shikimic acid in the biosynthesis of vitamin K2.](https://pubmed.ncbi.nlm.nih.gov/5337721/) [Biosynthesis of ubiquinone in Escherichia coli K-12: biochemical and genetic characterization of a mutant unable to convert chorismate into 4-hydroxybenzoate.](https://pubmed.ncbi.nlm.nih.gov/4595202/)
Complete structured claim and evidence
Isotope-labeled methionine contributed carbon to E. coli MK-8 in the historical labeling experiment.
L-Methionine → Menaquinone-8 / MK-8 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
E. coli 1966 isotope tracing; shikimate ring carbon versus methionine methyl carbon.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Carbon incorporation, not complete enzymatic sequence, human MK-7 production or oral vitamin-K efficacy.
plain_language
Isotope-labeled methionine contributed carbon to E. coli MK-8 in the historical labeling experiment.
primary_references
Biosynthesis of ubiquinone in Escherichia coli K-12: biochemical and genetic characterization of a mutant unable to convert chorismate into 4-hydroxybenzoate. | 1974 | DOI 10.1128/jb.118.1.41-45.1974 | PMID 4595202 | https://pubmed.ncbi.nlm.nih.gov/4595202/ | https://doi.org/10.1128/jb.118.1.41-45.1974 | https://pmc.ncbi.nlm.nih.gov/articles/PMC246637/
primary_references
The role of shikimic acid in the biosynthesis of vitamin K2. | 1966 | DOI 10.1042/bj1000001 | PMID 5337721 | https://pubmed.ncbi.nlm.nih.gov/5337721/ | https://doi.org/10.1042/bj1000001 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1265084/
source_locator
Reviewed reference lines 27-27; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 27–27
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli 1966 isotope tracing; shikimate ring carbon versus methionine methyl carbon. · Recorded from source · Recorded from source
**The K and Q branches are organism-specific.** Isotope experiments in E. coli traced shikimate carbon into the benzene ring of menaquinone-8 (MK-8), and methionine-derived methyl carbon into that product. This does not establish increased human MK-7, vitamin-K function or an oral shikimate dose response. Separately, an E. coli ubiC mutant failed to convert chorismate to 4-hydroxybenzoate and produced little ubiquinone unless supplied with 4-hydroxybenzoate. UbiC therefore identifies a branch-specific supply bottleneck; bacterial ubiquinone production is not synonymous with human mitochondrial CoQ10 synthesis. [The role of shikimic acid in the biosynthesis of vitamin K2.](https://pubmed.ncbi.nlm.nih.gov/5337721/) [Biosynthesis of ubiquinone in Escherichia coli K-12: biochemical and genetic characterization of a mutant unable to convert chorismate into 4-hydroxybenzoate.](https://pubmed.ncbi.nlm.nih.gov/4595202/)
Complete structured claim and evidence
E. coli UbiC converts chorismate toward the 4-hydroxybenzoate precursor of bacterial ubiquinone.
Chorismate → 4-Hydroxybenzoate Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
E. coli UbiC converts chorismate toward the 4-hydroxybenzoate precursor of bacterial ubiquinone.
primary_references
Biosynthesis of ubiquinone in Escherichia coli K-12: biochemical and genetic characterization of a mutant unable to convert chorismate into 4-hydroxybenzoate. | 1974 | DOI 10.1128/jb.118.1.41-45.1974 | PMID 4595202 | https://pubmed.ncbi.nlm.nih.gov/4595202/ | https://doi.org/10.1128/jb.118.1.41-45.1974 | https://pmc.ncbi.nlm.nih.gov/articles/PMC246637/
primary_references
The role of shikimic acid in the biosynthesis of vitamin K2. | 1966 | DOI 10.1042/bj1000001 | PMID 5337721 | https://pubmed.ncbi.nlm.nih.gov/5337721/ | https://doi.org/10.1042/bj1000001 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1265084/
source_locator
Reviewed reference lines 27-27; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 27–27
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Escherichia coli biochemical pathway; source-specific enzyme evidence recorded in the passage. · Recorded from source · Recorded from source
**The K and Q branches are organism-specific.** Isotope experiments in E. coli traced shikimate carbon into the benzene ring of menaquinone-8 (MK-8), and methionine-derived methyl carbon into that product. This does not establish increased human MK-7, vitamin-K function or an oral shikimate dose response. Separately, an E. coli ubiC mutant failed to convert chorismate to 4-hydroxybenzoate and produced little ubiquinone unless supplied with 4-hydroxybenzoate. UbiC therefore identifies a branch-specific supply bottleneck; bacterial ubiquinone production is not synonymous with human mitochondrial CoQ10 synthesis. [The role of shikimic acid in the biosynthesis of vitamin K2.](https://pubmed.ncbi.nlm.nih.gov/5337721/) [Biosynthesis of ubiquinone in Escherichia coli K-12: biochemical and genetic characterization of a mutant unable to convert chorismate into 4-hydroxybenzoate.](https://pubmed.ncbi.nlm.nih.gov/4595202/)
Complete structured claim and evidence
The ubiC mutant produced little ubiquinone without exogenous 4-hydroxybenzoate.
Escherichia coli chorismate pyruvate-lyase / UbiC → E. coli ubiquinone biosynthesis Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_contrast
{"intervention": "ubiC-defective strain without external 4-hydroxybenzoate", "comparator": "UbiC-functional or precursor-rescued background", "endpoint": "The ubiC mutant produced little ubiquinone without exogenous 4-hydroxybenzoate.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
E. coli K12 mutant characterization.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
The ubiC mutant produced little ubiquinone without exogenous 4-hydroxybenzoate.
primary_references
Biosynthesis of ubiquinone in Escherichia coli K-12: biochemical and genetic characterization of a mutant unable to convert chorismate into 4-hydroxybenzoate. | 1974 | DOI 10.1128/jb.118.1.41-45.1974 | PMID 4595202 | https://pubmed.ncbi.nlm.nih.gov/4595202/ | https://doi.org/10.1128/jb.118.1.41-45.1974 | https://pmc.ncbi.nlm.nih.gov/articles/PMC246637/
primary_references
The role of shikimic acid in the biosynthesis of vitamin K2. | 1966 | DOI 10.1042/bj1000001 | PMID 5337721 | https://pubmed.ncbi.nlm.nih.gov/5337721/ | https://doi.org/10.1042/bj1000001 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1265084/
source_locator
Reviewed reference lines 27-27; exact primary location described in quoted passage where extracted.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 27–27
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli K12 mutant characterization. · Recorded from source · Recorded from source
**The K and Q branches are organism-specific.** Isotope experiments in E. coli traced shikimate carbon into the benzene ring of menaquinone-8 (MK-8), and methionine-derived methyl carbon into that product. This does not establish increased human MK-7, vitamin-K function or an oral shikimate dose response. Separately, an E. coli ubiC mutant failed to convert chorismate to 4-hydroxybenzoate and produced little ubiquinone unless supplied with 4-hydroxybenzoate. UbiC therefore identifies a branch-specific supply bottleneck; bacterial ubiquinone production is not synonymous with human mitochondrial CoQ10 synthesis. [The role of shikimic acid in the biosynthesis of vitamin K2.](https://pubmed.ncbi.nlm.nih.gov/5337721/) [Biosynthesis of ubiquinone in Escherichia coli K-12: biochemical and genetic characterization of a mutant unable to convert chorismate into 4-hydroxybenzoate.](https://pubmed.ncbi.nlm.nih.gov/4595202/)
Complete structured claim and evidence
External 4-hydroxybenzoate restored the precursor supply supporting ubiquinone production in ubiC-defective E. coli.
4-Hydroxybenzoate → E. coli ubiquinone biosynthesis Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_condition
Same mutant without supplied precursor supplied · 4-Hydroxybenzoate Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
Same mutant without supplied precursor defective · Escherichia coli chorismate pyruvate-lyase / UbiC Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "4-Hydroxybenzoate supplied to ubiC mutant", "comparator": "Same mutant without supplied precursor", "endpoint": "External 4-hydroxybenzoate restored the precursor supply supporting ubiquinone production in ubiC-defective E. coli.", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "ecoli-ubic", "state": "defective"}, {"entity_slug": "4-hydroxybenzoate", "state": "supplied"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
E. coli K12 precursor-rescue experiment.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
External 4-hydroxybenzoate restored the precursor supply supporting ubiquinone production in ubiC-defective E. coli.
primary_references
Biosynthesis of ubiquinone in Escherichia coli K-12: biochemical and genetic characterization of a mutant unable to convert chorismate into 4-hydroxybenzoate. | 1974 | DOI 10.1128/jb.118.1.41-45.1974 | PMID 4595202 | https://pubmed.ncbi.nlm.nih.gov/4595202/ | https://doi.org/10.1128/jb.118.1.41-45.1974 | https://pmc.ncbi.nlm.nih.gov/articles/PMC246637/
primary_references
The role of shikimic acid in the biosynthesis of vitamin K2. | 1966 | DOI 10.1042/bj1000001 | PMID 5337721 | https://pubmed.ncbi.nlm.nih.gov/5337721/ | https://doi.org/10.1042/bj1000001 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1265084/
source_locator
Reviewed reference lines 27-27; exact primary location described in quoted passage where extracted.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 27–27
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · E. coli K12 precursor-rescue experiment. · Recorded from source · Recorded from source
**The K and Q branches are organism-specific.** Isotope experiments in E. coli traced shikimate carbon into the benzene ring of menaquinone-8 (MK-8), and methionine-derived methyl carbon into that product. This does not establish increased human MK-7, vitamin-K function or an oral shikimate dose response. Separately, an E. coli ubiC mutant failed to convert chorismate to 4-hydroxybenzoate and produced little ubiquinone unless supplied with 4-hydroxybenzoate. UbiC therefore identifies a branch-specific supply bottleneck; bacterial ubiquinone production is not synonymous with human mitochondrial CoQ10 synthesis. [The role of shikimic acid in the biosynthesis of vitamin K2.](https://pubmed.ncbi.nlm.nih.gov/5337721/) [Biosynthesis of ubiquinone in Escherichia coli K-12: biochemical and genetic characterization of a mutant unable to convert chorismate into 4-hydroxybenzoate.](https://pubmed.ncbi.nlm.nih.gov/4595202/)
Complete structured claim and evidence
Cecally supplied labeled folate appeared in plasma as labeled 5-methyltetrahydrofolate in six healthy adults.
5-Formyltetrahydrofolate → Human plasma appearance of cecally administered labeled folate Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text HTML and indexed abstract reviewed for the stated results; archived locally.
experimental_model
Cecal 684-nmol isotope administration; separate intravenous comparator.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Absorption of supplied folate, not measurement of daily microbial vitamin contribution or shikimate supplementation.
plain_language
Cecally supplied labeled folate appeared in plasma as labeled 5-methyltetrahydrofolate in six healthy adults.
primary_references
Folate is absorbed across the colon of adults: evidence from cecal infusion of (13)C-labeled [6S]-5-formyltetrahydrofolic acid. | 2009 | DOI 10.3945/ajcn.2008.27345 | PMID 19439459 | https://pubmed.ncbi.nlm.nih.gov/19439459/ | https://doi.org/10.3945/ajcn.2008.27345 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6443296/
source_locator
Reviewed reference lines 29-29; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 29–29
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Cecal 684-nmol isotope administration; separate intravenous comparator. · Recorded from source · Recorded from source
**Production and absorption are separate questions.** A human stable-isotope study delivered 684 nmol (320 µg) of labeled [6S]-5-formyltetrahydrofolate to the cecum of six healthy adults. Labeled 5-methyltetrahydrofolate appeared in plasma; appearance was about 0.6 ± 0.2 nmol/h versus 7 ± 1.2 nmol/h after a separate 172-nmol intravenous administration. This demonstrates colonic absorption of a supplied folate preparation under the study conditions. It does not quantify habitual microbial folate contribution, prove a shikimate intervention, or establish equal absorption of every microbial folate form. [Folate is absorbed across the colon of adults: evidence from cecal infusion of (13)C-labeled [6S]-5-formyltetrahydrofolic acid.](https://pubmed.ncbi.nlm.nih.gov/19439459/)
Complete structured claim and evidence
Longitudinal fecal menaquinone patterns did not associate significantly with glycemia, insulin resistance or inflammatory markers in the recorded cohort.
Vitamin K2 / menaquinone family → Human fecal menaquinone association with glycemia, insulin resistance and inflammation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
77 overweight Chinese adults during a diet intervention.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Observational association null; not proof of absence of every vitamin-K effect or absorbed exposure.
plain_language
Longitudinal fecal menaquinone patterns did not associate significantly with glycemia, insulin resistance or inflammatory markers in the recorded cohort.
primary_references
Fecal menaquinone profiles of overweight adults are associated with gut microbiota composition during a gut microbiota-targeted dietary intervention. | 2015 | DOI 10.3945/ajcn.115.109496 | PMID 26016865 | https://pubmed.ncbi.nlm.nih.gov/26016865/ | https://doi.org/10.3945/ajcn.115.109496
primary_references
Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. | 2010 | DOI 10.1038/nature09464 | PMID 20953171 | https://pubmed.ncbi.nlm.nih.gov/20953171/ | https://doi.org/10.1038/nature09464
source_locator
Reviewed reference lines 31-31; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 31–31
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · 77 overweight Chinese adults during a diet intervention. · Recorded from source · Recorded from source
**Fecal vitamin K is not absorbed vitamin K.** In 77 overweight Chinese adults, fecal menaquinone patterns associated with microbial composition. A diet intervention decreased fecal MK-4, MK-6 and MK-8, but longitudinal menaquinone patterns did not associate with glycemia, insulin resistance or inflammation. Separately, human UBIAD1 silencing reduced MK-4 biosynthesis in labeled-precursor experiments; UBIAD1 is a host prenyltransferase, not a shikimate-pathway enzyme. Neither result proves that microbial shikimate output determines tissue vitamin-K adequacy. [Fecal menaquinone profiles of overweight adults are associated with gut microbiota composition during a gut microbiota-targeted dietary intervention.](https://pubmed.ncbi.nlm.nih.gov/26016865/) [Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme.](https://pubmed.ncbi.nlm.nih.gov/20953171/)
Complete structured claim and evidence
Silencing human UBIAD1 reduced labeled-precursor MK-4 biosynthesis.
Human UBIAD1 prenyltransferase → Menaquinone-4 biosynthesis Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_contrast
{"intervention": "UBIAD1 silencing", "comparator": "Matched functional UBIAD1 background", "endpoint": "Silencing human UBIAD1 reduced labeled-precursor MK-4 biosynthesis.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human cellular gene-silencing and enzyme studies.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Host prenylation route; no human shikimate pathway is implied.
plain_language
Silencing human UBIAD1 reduced labeled-precursor MK-4 biosynthesis.
primary_references
Fecal menaquinone profiles of overweight adults are associated with gut microbiota composition during a gut microbiota-targeted dietary intervention. | 2015 | DOI 10.3945/ajcn.115.109496 | PMID 26016865 | https://pubmed.ncbi.nlm.nih.gov/26016865/ | https://doi.org/10.3945/ajcn.115.109496
primary_references
Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. | 2010 | DOI 10.1038/nature09464 | PMID 20953171 | https://pubmed.ncbi.nlm.nih.gov/20953171/ | https://doi.org/10.1038/nature09464
source_locator
Reviewed reference lines 31-31; exact primary location described in quoted passage where extracted.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 31–31
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human cellular gene-silencing and enzyme studies. · Recorded from source · Recorded from source
**Fecal vitamin K is not absorbed vitamin K.** In 77 overweight Chinese adults, fecal menaquinone patterns associated with microbial composition. A diet intervention decreased fecal MK-4, MK-6 and MK-8, but longitudinal menaquinone patterns did not associate with glycemia, insulin resistance or inflammation. Separately, human UBIAD1 silencing reduced MK-4 biosynthesis in labeled-precursor experiments; UBIAD1 is a host prenyltransferase, not a shikimate-pathway enzyme. Neither result proves that microbial shikimate output determines tissue vitamin-K adequacy. [Fecal menaquinone profiles of overweight adults are associated with gut microbiota composition during a gut microbiota-targeted dietary intervention.](https://pubmed.ncbi.nlm.nih.gov/26016865/) [Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme.](https://pubmed.ncbi.nlm.nih.gov/20953171/)
Complete structured claim and evidence
dp-ucMGP interpretation is associated with kidney function in the transplant cohort.
Vitamin K2 / menaquinone family → Association of human dp-ucMGP with renal function Recorded from sourceungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Kidney-transplant observational cohort; biomarker context.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Not source-specific vitamin K, proof of microbial depletion, or an isolated renal-clearance mechanism.
plain_language
dp-ucMGP interpretation is associated with kidney function in the transplant cohort.
primary_references
Kidney Function-Dependence of Vitamin K-Status Parameters: Results from the TransplantLines Biobank and Cohort Studies. | 2021 | DOI 10.3390/nu13093069 | PMID 34578950 | https://pubmed.ncbi.nlm.nih.gov/34578950/ | https://doi.org/10.3390/nu13093069 | https://pmc.ncbi.nlm.nih.gov/articles/PMC8467091/
source_locator
Reviewed reference lines 33-33; exact primary location described in quoted passage where extracted.
trigger_kind
biomarker_context Imported condition classification; unverified.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 33–33
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Kidney-transplant observational cohort; biomarker context. · Recorded from source · Recorded from source
**Kidney function complicates dp-ucMGP interpretation.** The kidney-transplant study associated lower estimated GFR with higher circulating dp-ucMGP, and recorded a large fall after transplantation. This is a biomarker-context observation, not an assay identifying the microbial origin of vitamin K or isolating renal clearance as the only explanation. A related published comment exists and causal interpretation remains open. A correlation among glyphosate exposure, fecal menaquinones and dp-ucMGP would not by itself establish the entire proposed causal chain. [Kidney Function-Dependence of Vitamin K-Status Parameters: Results from the TransplantLines Biobank and Cohort Studies.](https://pubmed.ncbi.nlm.nih.gov/34578950/)
Complete structured claim and evidence
Environmental aromatic-amino-acid availability modified bacterial susceptibility in the two-week glyphosate study.
Glyphosate → Rat/microbial glyphosate response with environmental aromatic amino acids Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Nielsen 2018 rats and microbial nutrient-context assays.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
No universal gut effect threshold or assertion that every metabolic function remained unchanged.
plain_language
Environmental aromatic-amino-acid availability modified bacterial susceptibility in the two-week glyphosate study.
primary_references
Glyphosate has limited short-term effects on commensal bacterial community composition in the gut environment due to sufficient aromatic amino acid levels. | 2018 | DOI 10.1016/j.envpol.2017.10.016 | PMID 29096310 | https://pubmed.ncbi.nlm.nih.gov/29096310/ | https://doi.org/10.1016/j.envpol.2017.10.016
source_locator
Reviewed reference lines 35-35; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 35–35
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Nielsen 2018 rats and microbial nutrient-context assays. · Recorded from source · Recorded from source
**Nutrient environment changes glyphosate sensitivity.** Nielsen 2018 tested pure glyphosate and Glyfonova 450 PLUS in rats for two weeks, including 25 mg/kg/day. Community-composition effects were limited in that setting; bacterial responses depended on available aromatic amino acids. This is not a blanket null for every microbial function. The study also reported reduced acetate and correlations involving intestinal glyphosate concentration and pH. Preserve compound, preparation, duration and nutrient conditions instead of declaring all bacteria uniformly resistant or sensitive. [Glyphosate has limited short-term effects on commensal bacterial community composition in the gut environment due to sufficient aromatic amino acid levels.](https://pubmed.ncbi.nlm.nih.gov/29096310/)
Complete structured claim and evidence
The 90-day glyphosate study recorded cecal shikimate accumulation consistent with pathway inhibition.
Glyphosate → Rat cecal shikimate accumulation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Female Sprague–Dawley rats; 0.5, 50 and 175 mg/kg/day glyphosate-equivalent groups; 12/group.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Study-level direction; no unsupported per-dose significance claim. Pool accumulation is not increased downstream flux.
plain_language
The 90-day glyphosate study recorded cecal shikimate accumulation consistent with pathway inhibition.
primary_references
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. | 2021 | DOI 10.1289/ehp6990 | PMID 33502259 | https://pubmed.ncbi.nlm.nih.gov/33502259/ | https://doi.org/10.1289/ehp6990 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7839352/
source_locator
Reviewed reference lines 37-37; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 37–37
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Female Sprague–Dawley rats; 0.5, 50 and 175 mg/kg/day glyphosate-equivalent groups; 12/group. · Recorded from source · Recorded from source
**An upstream pool can rise when flux is blocked.** Mesnage 2021 compared pure glyphosate and Roundup MON52276 in female Sprague–Dawley rats for 90 days at 0.5, 50 and 175 mg/kg/day glyphosate-equivalent exposures, with 12 animals per group. Cecal shikimate and DHS accumulation supported pathway inhibition; abundance alone was less informative. The collection records study-level accumulation rather than asserting every dose had an identical significant effect. Overall alpha-diversity differences were not significant (p=0.09), while beta diversity differed. Selected low-abundance taxa changed, and formulation-specific differences remained. Serum shikimate was undetected with the employed method, whose sensitivity and protein interference limit a zero-exposure interpretation. [Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.](https://pubmed.ncbi.nlm.nih.gov/33502259/)
Complete structured claim and evidence
The 90-day glyphosate study recorded cecal 3-dehydroshikimate accumulation consistent with pathway inhibition.
Glyphosate → Rat cecal DHS accumulation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Female Sprague–Dawley rats; 0.5, 50 and 175 mg/kg/day glyphosate-equivalent groups; 12/group.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Study-level direction; no unsupported per-dose significance claim. Pool accumulation is not increased downstream flux.
plain_language
The 90-day glyphosate study recorded cecal 3-dehydroshikimate accumulation consistent with pathway inhibition.
primary_references
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. | 2021 | DOI 10.1289/ehp6990 | PMID 33502259 | https://pubmed.ncbi.nlm.nih.gov/33502259/ | https://doi.org/10.1289/ehp6990 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7839352/
source_locator
Reviewed reference lines 37-37; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 37–37
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Female Sprague–Dawley rats; 0.5, 50 and 175 mg/kg/day glyphosate-equivalent groups; 12/group. · Recorded from source · Recorded from source
**An upstream pool can rise when flux is blocked.** Mesnage 2021 compared pure glyphosate and Roundup MON52276 in female Sprague–Dawley rats for 90 days at 0.5, 50 and 175 mg/kg/day glyphosate-equivalent exposures, with 12 animals per group. Cecal shikimate and DHS accumulation supported pathway inhibition; abundance alone was less informative. The collection records study-level accumulation rather than asserting every dose had an identical significant effect. Overall alpha-diversity differences were not significant (p=0.09), while beta diversity differed. Selected low-abundance taxa changed, and formulation-specific differences remained. Serum shikimate was undetected with the employed method, whose sensitivity and protein interference limit a zero-exposure interpretation. [Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.](https://pubmed.ncbi.nlm.nih.gov/33502259/)
Complete structured claim and evidence
The 90-day roundup-mon52276 study recorded cecal shikimate accumulation consistent with pathway inhibition.
Roundup MON52276, tested glyphosate formulation → Rat cecal shikimate accumulation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Female Sprague–Dawley rats; 0.5, 50 and 175 mg/kg/day glyphosate-equivalent groups; 12/group.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Study-level direction; no unsupported per-dose significance claim. Pool accumulation is not increased downstream flux.
plain_language
The 90-day roundup-mon52276 study recorded cecal shikimate accumulation consistent with pathway inhibition.
primary_references
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. | 2021 | DOI 10.1289/ehp6990 | PMID 33502259 | https://pubmed.ncbi.nlm.nih.gov/33502259/ | https://doi.org/10.1289/ehp6990 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7839352/
source_locator
Reviewed reference lines 37-37; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 37–37
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Female Sprague–Dawley rats; 0.5, 50 and 175 mg/kg/day glyphosate-equivalent groups; 12/group. · Recorded from source · Recorded from source
**An upstream pool can rise when flux is blocked.** Mesnage 2021 compared pure glyphosate and Roundup MON52276 in female Sprague–Dawley rats for 90 days at 0.5, 50 and 175 mg/kg/day glyphosate-equivalent exposures, with 12 animals per group. Cecal shikimate and DHS accumulation supported pathway inhibition; abundance alone was less informative. The collection records study-level accumulation rather than asserting every dose had an identical significant effect. Overall alpha-diversity differences were not significant (p=0.09), while beta diversity differed. Selected low-abundance taxa changed, and formulation-specific differences remained. Serum shikimate was undetected with the employed method, whose sensitivity and protein interference limit a zero-exposure interpretation. [Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.](https://pubmed.ncbi.nlm.nih.gov/33502259/)
Complete structured claim and evidence
The 90-day roundup-mon52276 study recorded cecal 3-dehydroshikimate accumulation consistent with pathway inhibition.
Roundup MON52276, tested glyphosate formulation → Rat cecal DHS accumulation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Female Sprague–Dawley rats; 0.5, 50 and 175 mg/kg/day glyphosate-equivalent groups; 12/group.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Study-level direction; no unsupported per-dose significance claim. Pool accumulation is not increased downstream flux.
plain_language
The 90-day roundup-mon52276 study recorded cecal 3-dehydroshikimate accumulation consistent with pathway inhibition.
primary_references
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. | 2021 | DOI 10.1289/ehp6990 | PMID 33502259 | https://pubmed.ncbi.nlm.nih.gov/33502259/ | https://doi.org/10.1289/ehp6990 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7839352/
source_locator
Reviewed reference lines 37-37; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 37–37
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Female Sprague–Dawley rats; 0.5, 50 and 175 mg/kg/day glyphosate-equivalent groups; 12/group. · Recorded from source · Recorded from source
**An upstream pool can rise when flux is blocked.** Mesnage 2021 compared pure glyphosate and Roundup MON52276 in female Sprague–Dawley rats for 90 days at 0.5, 50 and 175 mg/kg/day glyphosate-equivalent exposures, with 12 animals per group. Cecal shikimate and DHS accumulation supported pathway inhibition; abundance alone was less informative. The collection records study-level accumulation rather than asserting every dose had an identical significant effect. Overall alpha-diversity differences were not significant (p=0.09), while beta diversity differed. Selected low-abundance taxa changed, and formulation-specific differences remained. Serum shikimate was undetected with the employed method, whose sensitivity and protein interference limit a zero-exposure interpretation. [Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.](https://pubmed.ncbi.nlm.nih.gov/33502259/)
Complete structured claim and evidence
Overall alpha-diversity differences in the study were not significant (p=0.09).
Glyphosate → Rat microbiome alpha diversity Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Across glyphosate and MON52276 treatment groups in the 90-day rat study.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Diversity null does not erase metabolomic differences or establish absence of biological effect.
plain_language
Overall alpha-diversity differences in the study were not significant (p=0.09).
primary_references
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. | 2021 | DOI 10.1289/ehp6990 | PMID 33502259 | https://pubmed.ncbi.nlm.nih.gov/33502259/ | https://doi.org/10.1289/ehp6990 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7839352/
source_locator
Reviewed reference lines 37-37; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 37–37
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Across glyphosate and MON52276 treatment groups in the 90-day rat study. · Recorded from source · Recorded from source
**An upstream pool can rise when flux is blocked.** Mesnage 2021 compared pure glyphosate and Roundup MON52276 in female Sprague–Dawley rats for 90 days at 0.5, 50 and 175 mg/kg/day glyphosate-equivalent exposures, with 12 animals per group. Cecal shikimate and DHS accumulation supported pathway inhibition; abundance alone was less informative. The collection records study-level accumulation rather than asserting every dose had an identical significant effect. Overall alpha-diversity differences were not significant (p=0.09), while beta diversity differed. Selected low-abundance taxa changed, and formulation-specific differences remained. Serum shikimate was undetected with the employed method, whose sensitivity and protein interference limit a zero-exposure interpretation. [Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.](https://pubmed.ncbi.nlm.nih.gov/33502259/)
Complete structured claim and evidence
Serum shikimate was not detected by the reported analytical method in the 90-day study.
Glyphosate → Rat serum shikimate detection in the Mesnage assay Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Rat serum assay with matrix and sensitivity limitations.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Non-detection is not zero concentration, proof of no absorption or a measured decline.
plain_language
Serum shikimate was not detected by the reported analytical method in the 90-day study.
primary_references
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. | 2021 | DOI 10.1289/ehp6990 | PMID 33502259 | https://pubmed.ncbi.nlm.nih.gov/33502259/ | https://doi.org/10.1289/ehp6990 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7839352/
source_locator
Reviewed reference lines 37-37; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 37–37
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Rat serum assay with matrix and sensitivity limitations. · Recorded from source · Recorded from source
**An upstream pool can rise when flux is blocked.** Mesnage 2021 compared pure glyphosate and Roundup MON52276 in female Sprague–Dawley rats for 90 days at 0.5, 50 and 175 mg/kg/day glyphosate-equivalent exposures, with 12 animals per group. Cecal shikimate and DHS accumulation supported pathway inhibition; abundance alone was less informative. The collection records study-level accumulation rather than asserting every dose had an identical significant effect. Overall alpha-diversity differences were not significant (p=0.09), while beta diversity differed. Selected low-abundance taxa changed, and formulation-specific differences remained. Serum shikimate was undetected with the employed method, whose sensitivity and protein interference limit a zero-exposure interpretation. [Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.](https://pubmed.ncbi.nlm.nih.gov/33502259/)
Complete structured claim and evidence
GT+ reduced L. rhamnosus growth in the tested comparison.
Roundup GT+, tested glyphosate formulation → Lactobacillus rhamnosus growth in formulation-comparison assays Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "roundup-gt-plus at the reported tested concentration", "comparator": "Matched culture without formulation", "endpoint": "GT+ reduced L. rhamnosus growth in the tested comparison.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Bacterial culture comparison separate from the rat study.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Specific formulation and concentration comparison, not universal absence or presence of inhibition.
plain_language
GT+ reduced L. rhamnosus growth in the tested comparison.
primary_references
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. | 2021 | DOI 10.1289/ehp6990 | PMID 33502259 | https://pubmed.ncbi.nlm.nih.gov/33502259/ | https://doi.org/10.1289/ehp6990 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7839352/
source_locator
Reviewed reference lines 39-39; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 39–39
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Bacterial culture comparison separate from the rat study. · Recorded from source · Recorded from source
**Microbial metabolites do not automatically establish host deficiency.** The same rat study recorded cecal changes in cysteinylglycine, gamma-glutamylglutamine and valylglycine, among other metabolites. These pools are not direct measurements of host glutathione synthesis, nutrient sufficiency or pathway flux. In separate bacterial culture comparisons, Roundup GT+ suppressed L. rhamnosus growth under conditions where pure glyphosate and MON52276 did not. Formulations therefore retain separate actor identities. A dose in mg/kg/day cannot be converted into a microbial mM exposure without measured concentration, distribution and time. [Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.](https://pubmed.ncbi.nlm.nih.gov/33502259/)
Complete structured claim and evidence
Pure glyphosate did not inhibit growth under the cited GT+-sensitive test conditions.
Glyphosate → Lactobacillus rhamnosus growth in formulation-comparison assays Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "glyphosate at the reported tested concentration", "comparator": "Matched culture without formulation", "endpoint": "Pure glyphosate did not inhibit growth under the cited GT+-sensitive test conditions.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Bacterial culture comparison separate from the rat study.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Specific formulation and concentration comparison, not universal absence or presence of inhibition.
plain_language
Pure glyphosate did not inhibit growth under the cited GT+-sensitive test conditions.
primary_references
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. | 2021 | DOI 10.1289/ehp6990 | PMID 33502259 | https://pubmed.ncbi.nlm.nih.gov/33502259/ | https://doi.org/10.1289/ehp6990 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7839352/
source_locator
Reviewed reference lines 39-39; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 39–39
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Bacterial culture comparison separate from the rat study. · Recorded from source · Recorded from source
**Microbial metabolites do not automatically establish host deficiency.** The same rat study recorded cecal changes in cysteinylglycine, gamma-glutamylglutamine and valylglycine, among other metabolites. These pools are not direct measurements of host glutathione synthesis, nutrient sufficiency or pathway flux. In separate bacterial culture comparisons, Roundup GT+ suppressed L. rhamnosus growth under conditions where pure glyphosate and MON52276 did not. Formulations therefore retain separate actor identities. A dose in mg/kg/day cannot be converted into a microbial mM exposure without measured concentration, distribution and time. [Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.](https://pubmed.ncbi.nlm.nih.gov/33502259/)
Complete structured claim and evidence
MON52276 did not inhibit growth under the cited GT+-sensitive test conditions.
Roundup MON52276, tested glyphosate formulation → Lactobacillus rhamnosus growth in formulation-comparison assays Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "roundup-mon52276 at the reported tested concentration", "comparator": "Matched culture without formulation", "endpoint": "MON52276 did not inhibit growth under the cited GT+-sensitive test conditions.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Bacterial culture comparison separate from the rat study.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Specific formulation and concentration comparison, not universal absence or presence of inhibition.
plain_language
MON52276 did not inhibit growth under the cited GT+-sensitive test conditions.
primary_references
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. | 2021 | DOI 10.1289/ehp6990 | PMID 33502259 | https://pubmed.ncbi.nlm.nih.gov/33502259/ | https://doi.org/10.1289/ehp6990 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7839352/
source_locator
Reviewed reference lines 39-39; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 39–39
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Bacterial culture comparison separate from the rat study. · Recorded from source · Recorded from source
**Microbial metabolites do not automatically establish host deficiency.** The same rat study recorded cecal changes in cysteinylglycine, gamma-glutamylglutamine and valylglycine, among other metabolites. These pools are not direct measurements of host glutathione synthesis, nutrient sufficiency or pathway flux. In separate bacterial culture comparisons, Roundup GT+ suppressed L. rhamnosus growth under conditions where pure glyphosate and MON52276 did not. Formulations therefore retain separate actor identities. A dose in mg/kg/day cannot be converted into a microbial mM exposure without measured concentration, distribution and time. [Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.](https://pubmed.ncbi.nlm.nih.gov/33502259/)
Complete structured claim and evidence
The rat glyphosate/formulation study recorded increased cecal cysteinylglycine.
Glyphosate → Rat cecal cysteinylglycine pool Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
90-day rat metabolomics; study-level observed pool change.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Not direct host glutathione flux, nutrient depletion, or per-dose replicated effect.
plain_language
The rat glyphosate/formulation study recorded increased cecal cysteinylglycine.
primary_references
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. | 2021 | DOI 10.1289/ehp6990 | PMID 33502259 | https://pubmed.ncbi.nlm.nih.gov/33502259/ | https://doi.org/10.1289/ehp6990 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7839352/
source_locator
Reviewed reference lines 39-39; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 39–39
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · 90-day rat metabolomics; study-level observed pool change. · Recorded from source · Recorded from source
**Microbial metabolites do not automatically establish host deficiency.** The same rat study recorded cecal changes in cysteinylglycine, gamma-glutamylglutamine and valylglycine, among other metabolites. These pools are not direct measurements of host glutathione synthesis, nutrient sufficiency or pathway flux. In separate bacterial culture comparisons, Roundup GT+ suppressed L. rhamnosus growth under conditions where pure glyphosate and MON52276 did not. Formulations therefore retain separate actor identities. A dose in mg/kg/day cannot be converted into a microbial mM exposure without measured concentration, distribution and time. [Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.](https://pubmed.ncbi.nlm.nih.gov/33502259/)
Complete structured claim and evidence
The rat glyphosate/formulation study recorded increased cecal gamma-glutamylglutamine.
Glyphosate → Rat cecal gamma-glutamylglutamine pool Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
90-day rat metabolomics; study-level observed pool change.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Not direct host glutathione flux, nutrient depletion, or per-dose replicated effect.
plain_language
The rat glyphosate/formulation study recorded increased cecal gamma-glutamylglutamine.
primary_references
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. | 2021 | DOI 10.1289/ehp6990 | PMID 33502259 | https://pubmed.ncbi.nlm.nih.gov/33502259/ | https://doi.org/10.1289/ehp6990 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7839352/
source_locator
Reviewed reference lines 39-39; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 39–39
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · 90-day rat metabolomics; study-level observed pool change. · Recorded from source · Recorded from source
**Microbial metabolites do not automatically establish host deficiency.** The same rat study recorded cecal changes in cysteinylglycine, gamma-glutamylglutamine and valylglycine, among other metabolites. These pools are not direct measurements of host glutathione synthesis, nutrient sufficiency or pathway flux. In separate bacterial culture comparisons, Roundup GT+ suppressed L. rhamnosus growth under conditions where pure glyphosate and MON52276 did not. Formulations therefore retain separate actor identities. A dose in mg/kg/day cannot be converted into a microbial mM exposure without measured concentration, distribution and time. [Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.](https://pubmed.ncbi.nlm.nih.gov/33502259/)
Complete structured claim and evidence
The rat glyphosate/formulation study recorded increased cecal valylglycine.
Glyphosate → Rat cecal valylglycine pool Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
90-day rat metabolomics; study-level observed pool change.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Not direct host glutathione flux, nutrient depletion, or per-dose replicated effect.
plain_language
The rat glyphosate/formulation study recorded increased cecal valylglycine.
primary_references
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. | 2021 | DOI 10.1289/ehp6990 | PMID 33502259 | https://pubmed.ncbi.nlm.nih.gov/33502259/ | https://doi.org/10.1289/ehp6990 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7839352/
source_locator
Reviewed reference lines 39-39; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 39–39
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · 90-day rat metabolomics; study-level observed pool change. · Recorded from source · Recorded from source
**Microbial metabolites do not automatically establish host deficiency.** The same rat study recorded cecal changes in cysteinylglycine, gamma-glutamylglutamine and valylglycine, among other metabolites. These pools are not direct measurements of host glutathione synthesis, nutrient sufficiency or pathway flux. In separate bacterial culture comparisons, Roundup GT+ suppressed L. rhamnosus growth under conditions where pure glyphosate and MON52276 did not. Formulations therefore retain separate actor identities. A dose in mg/kg/day cannot be converted into a microbial mM exposure without measured concentration, distribution and time. [Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.](https://pubmed.ncbi.nlm.nih.gov/33502259/)
Complete structured claim and evidence
Human CES1 hydrolyzes oseltamivir to its carboxylate metabolite.
Oseltamivir → Oseltamivir carboxylate Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Human liver microsomes and recombinant human CES1; not human conversion of shikimic acid into oseltamivir.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
Human CES1 hydrolyzes oseltamivir to its carboxylate metabolite.
primary_references
Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. | 2006 | DOI 10.1124/jpet.106.111807 | PMID 16966469 | https://pubmed.ncbi.nlm.nih.gov/16966469/ | https://doi.org/10.1124/jpet.106.111807
source_locator
Reviewed reference lines 45-45; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 45–45
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human liver microsomes and recombinant human CES1; not human conversion of shikimic acid into oseltamivir. · Recorded from source · Recorded from source
**The prodrug has its own activation mechanism.** The oseltamivir prodrug is hydrolyzed to oseltamivir carboxylate by human CES1 in the studied human-liver/recombinant systems. CES2, intestinal microsomes and plasma did not show comparable activation in those assays. An in-vitro clopidogrel inhibition observation does not by itself establish loss of antiviral treatment efficacy; subsequent correspondence concerns that translation. These records belong to oseltamivir and CES1, not to a fictitious human shikimate-to-drug reaction. [Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel.](https://pubmed.ncbi.nlm.nih.gov/16966469/)
Complete structured claim and evidence
CES2 did not show comparable oseltamivir activation in the tested assays.
Human carboxylesterase 2 / CES2 → Oseltamivir carboxylate Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Recombinant human esterase comparison.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Assay-specific lack of conversion; not a general lack of CES2 activity.
plain_language
CES2 did not show comparable oseltamivir activation in the tested assays.
primary_references
Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. | 2006 | DOI 10.1124/jpet.106.111807 | PMID 16966469 | https://pubmed.ncbi.nlm.nih.gov/16966469/ | https://doi.org/10.1124/jpet.106.111807
source_locator
Reviewed reference lines 45-45; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 45–45
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Recombinant human esterase comparison. · Recorded from source · Recorded from source
**The prodrug has its own activation mechanism.** The oseltamivir prodrug is hydrolyzed to oseltamivir carboxylate by human CES1 in the studied human-liver/recombinant systems. CES2, intestinal microsomes and plasma did not show comparable activation in those assays. An in-vitro clopidogrel inhibition observation does not by itself establish loss of antiviral treatment efficacy; subsequent correspondence concerns that translation. These records belong to oseltamivir and CES1, not to a fictitious human shikimate-to-drug reaction. [Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel.](https://pubmed.ncbi.nlm.nih.gov/16966469/)
Complete structured claim and evidence
Nominal oral shikimic acid produced Cmax 904 ng/mL and estimated bioavailability 10.4% in rats.
Shikimic acid → Rat oral shikimic-acid exposure Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Male Sprague–Dawley rats, five per route; nominal oral 100 mg/kg versus intravenous 2 mg/kg.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Species/route-specific pharmacokinetic estimate, not human exposure. Rat nominal-dose arithmetic caveat and complete time parameters remain in the source passage.
plain_language
Nominal oral shikimic acid produced Cmax 904 ng/mL and estimated bioavailability 10.4% in rats.
primary_references
Pharmacokinetics of Shikimic Acid Following Intragastric and Intravenous Administrations in Rats. | 2020 | DOI 10.3390/pharmaceutics12090824 | PMID 32872397 | https://pubmed.ncbi.nlm.nih.gov/32872397/ | https://doi.org/10.3390/pharmaceutics12090824 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7558350/
source_locator
Reviewed reference lines 47-47; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 47–47
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Male Sprague–Dawley rats, five per route; nominal oral 100 mg/kg versus intravenous 2 mg/kg. · Recorded from source · Recorded from source
**Rat exposure is measurable but incomplete.** In five male Sprague–Dawley rats per route, reported oral shikimic acid 100 mg/kg produced Cmax 904 ± 48 ng/mL (calculated 5.19 µM), Tmax 2.7 ± 1.5 h and terminal half-life 1.26 ± 0.20 h. The intravenous comparator was 2 mg/kg; estimated absolute bioavailability was 10.4%. The Methods contains a dose/volume arithmetic inconsistency, so these are the nominal dose and Table 3 estimates, not an independently reconstructed administered dose. Occasional double peaks do not prove enterohepatic recycling. Neither rat transport mechanism nor human oral exposure is established by these numbers. [Pharmacokinetics of Shikimic Acid Following Intragastric and Intravenous Administrations in Rats.](https://pubmed.ncbi.nlm.nih.gov/32872397/)
Complete structured claim and evidence
Oral shikimic acid produced Cmax 10823.44 ng/mL and estimated bioavailability 21.68% in pigs.
Shikimic acid → Pig oral shikimic-acid exposure Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Six growing pigs, crossover; oral 50 mg/kg versus intravenous 2 mg/kg.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Species/route-specific pharmacokinetic estimate, not human exposure. Rat nominal-dose arithmetic caveat and complete time parameters remain in the source passage.
plain_language
Oral shikimic acid produced Cmax 10823.44 ng/mL and estimated bioavailability 21.68% in pigs.
primary_references
Pharmacokinetic-Pharmacodynamic Modeling of the Immune-Enhancing Effect of Shikimic Acid in Growing Pigs. | 2024 | DOI 10.1021/acs.jafc.4c09250 | PMID 39542831 | https://pubmed.ncbi.nlm.nih.gov/39542831/ | https://doi.org/10.1021/acs.jafc.4c09250 | https://pmc.ncbi.nlm.nih.gov/articles/PMC11613447/
source_locator
Reviewed reference lines 49-49; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 49–49
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Six growing pigs, crossover; oral 50 mg/kg versus intravenous 2 mg/kg. · Recorded from source · Recorded from source
**Pig exposure is not a human pharmacokinetic estimate.** In a six-pig crossover study, 50 mg/kg intragastric shikimic acid produced Cmax 10823.44 ng/mL (calculated 62.15 µM), Tmax 1.78 h and half-life 1.81 h. With a 2 mg/kg intravenous comparator, estimated bioavailability was 21.68%; intravenous half-life was 3.66 h. Rapid plasma C3, C4 and immunoglobulin changes correlated with drug concentration. This is not proof of new antibody synthesis or improved infection resistance. PK–PD fits to healthy pigs cannot supply an effective human dose. [Pharmacokinetic-Pharmacodynamic Modeling of the Immune-Enhancing Effect of Shikimic Acid in Growing Pigs.](https://pubmed.ncbi.nlm.nih.gov/39542831/)
Complete structured claim and evidence
Estimated oral shikimic-acid bioavailability was approximately 11.09–20.44% in the tested mice.
Shikimic acid → Mouse oral shikimic-acid exposure Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Mouse oral 50–100 mg/kg versus intravenous reference arms.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Species/route-specific pharmacokinetic estimate, not human exposure. Rat nominal-dose arithmetic caveat and complete time parameters remain in the source passage.
plain_language
Estimated oral shikimic-acid bioavailability was approximately 11.09–20.44% in the tested mice.
primary_references
Pharmacokinetic Profile and Evaluation of Acute and Subchronic Oral Toxicity of Shikimic Acid in Mice. | 2025 | DOI 10.1021/acsomega.5c03740 | PMID 40852254 | https://pubmed.ncbi.nlm.nih.gov/40852254/ | https://doi.org/10.1021/acsomega.5c03740 | https://pmc.ncbi.nlm.nih.gov/articles/PMC12368620/
source_locator
Reviewed reference lines 51-51; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 51–51
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse oral 50–100 mg/kg versus intravenous reference arms. · Recorded from source · Recorded from source
**Mouse distribution and bounded toxicity observations.** The 2025 mouse study reported intravenous half-lives approximately 0.76–0.85 h at 4–16 mg/kg and oral bioavailability approximately 11.09–20.44% at 50–100 mg/kg. A short plasma half-life does not prove unchanged renal excretion. In a separate 28-day feeding experiment, dietary concentrations were 5.56, 16.67 and 50 g/kg FEED, not mg/kg body weight. High-dose animals had small hematological shifts and lower triglycerides; acute survival through tested doses is not evidence of lifetime human safety. No validated human monocarboxylate-transporter assignment was found in the reviewed sources. [Pharmacokinetic Profile and Evaluation of Acute and Subchronic Oral Toxicity of Shikimic Acid in Mice.](https://pubmed.ncbi.nlm.nih.gov/40852254/)
Complete structured claim and evidence
Pig plasma complement/immunoglobulin changes correlated with shikimic-acid concentration.
Shikimic acid → Pig plasma complement and immunoglobulin concentration changes after shikimic acid Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Single-dose healthy-pig time-course and PK–PD association.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Not proof of new antibody synthesis or infection protection; no human dose inference.
plain_language
Pig plasma complement/immunoglobulin changes correlated with shikimic-acid concentration.
primary_references
Pharmacokinetic-Pharmacodynamic Modeling of the Immune-Enhancing Effect of Shikimic Acid in Growing Pigs. | 2024 | DOI 10.1021/acs.jafc.4c09250 | PMID 39542831 | https://pubmed.ncbi.nlm.nih.gov/39542831/ | https://doi.org/10.1021/acs.jafc.4c09250 | https://pmc.ncbi.nlm.nih.gov/articles/PMC11613447/
source_locator
Reviewed reference lines 49-49; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 49–49
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Single-dose healthy-pig time-course and PK–PD association. · Recorded from source · Recorded from source
**Pig exposure is not a human pharmacokinetic estimate.** In a six-pig crossover study, 50 mg/kg intragastric shikimic acid produced Cmax 10823.44 ng/mL (calculated 62.15 µM), Tmax 1.78 h and half-life 1.81 h. With a 2 mg/kg intravenous comparator, estimated bioavailability was 21.68%; intravenous half-life was 3.66 h. Rapid plasma C3, C4 and immunoglobulin changes correlated with drug concentration. This is not proof of new antibody synthesis or improved infection resistance. PK–PD fits to healthy pigs cannot supply an effective human dose. [Pharmacokinetic-Pharmacodynamic Modeling of the Immune-Enhancing Effect of Shikimic Acid in Growing Pigs.](https://pubmed.ncbi.nlm.nih.gov/39542831/)
Complete structured claim and evidence
The high-dose feeding group had lower triglycerides in the 28-day mouse study.
Shikimic acid → Mouse triglycerides after shikimic-acid feeding Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "50 g/kg feed for 28 days", "comparator": "Control feed", "endpoint": "The high-dose feeding group had lower triglycerides in the 28-day mouse study.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
ICR mice; 50 g shikimic acid per kg feed at the high dietary concentration.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Feed concentration is not body-weight dose; no demonstrated AMPK mediation or human efficacy.
plain_language
The high-dose feeding group had lower triglycerides in the 28-day mouse study.
primary_references
Pharmacokinetic Profile and Evaluation of Acute and Subchronic Oral Toxicity of Shikimic Acid in Mice. | 2025 | DOI 10.1021/acsomega.5c03740 | PMID 40852254 | https://pubmed.ncbi.nlm.nih.gov/40852254/ | https://doi.org/10.1021/acsomega.5c03740 | https://pmc.ncbi.nlm.nih.gov/articles/PMC12368620/
source_locator
Reviewed reference lines 51-51; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 51–51
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · ICR mice; 50 g shikimic acid per kg feed at the high dietary concentration. · Recorded from source · Recorded from source
**Mouse distribution and bounded toxicity observations.** The 2025 mouse study reported intravenous half-lives approximately 0.76–0.85 h at 4–16 mg/kg and oral bioavailability approximately 11.09–20.44% at 50–100 mg/kg. A short plasma half-life does not prove unchanged renal excretion. In a separate 28-day feeding experiment, dietary concentrations were 5.56, 16.67 and 50 g/kg FEED, not mg/kg body weight. High-dose animals had small hematological shifts and lower triglycerides; acute survival through tested doses is not evidence of lifetime human safety. No validated human monocarboxylate-transporter assignment was found in the reviewed sources. [Pharmacokinetic Profile and Evaluation of Acute and Subchronic Oral Toxicity of Shikimic Acid in Mice.](https://pubmed.ncbi.nlm.nih.gov/40852254/)
Complete structured claim and evidence
Small neutrophil, eosinophil and hematocrit increases occurred in the high-dose feeding group.
Shikimic acid → Mouse hematological changes after shikimic-acid feeding Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "High dietary shikimic-acid concentration", "comparator": "Control feed", "endpoint": "Small neutrophil, eosinophil and hematocrit increases occurred in the high-dose feeding group.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
ICR mice; 28-day feeding study.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Measured shifts do not establish beneficial immunity or long-term safety.
plain_language
Small neutrophil, eosinophil and hematocrit increases occurred in the high-dose feeding group.
primary_references
Pharmacokinetic Profile and Evaluation of Acute and Subchronic Oral Toxicity of Shikimic Acid in Mice. | 2025 | DOI 10.1021/acsomega.5c03740 | PMID 40852254 | https://pubmed.ncbi.nlm.nih.gov/40852254/ | https://doi.org/10.1021/acsomega.5c03740 | https://pmc.ncbi.nlm.nih.gov/articles/PMC12368620/
source_locator
Reviewed reference lines 51-51; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 51–51
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · ICR mice; 28-day feeding study. · Recorded from source · Recorded from source
**Mouse distribution and bounded toxicity observations.** The 2025 mouse study reported intravenous half-lives approximately 0.76–0.85 h at 4–16 mg/kg and oral bioavailability approximately 11.09–20.44% at 50–100 mg/kg. A short plasma half-life does not prove unchanged renal excretion. In a separate 28-day feeding experiment, dietary concentrations were 5.56, 16.67 and 50 g/kg FEED, not mg/kg body weight. High-dose animals had small hematological shifts and lower triglycerides; acute survival through tested doses is not evidence of lifetime human safety. No validated human monocarboxylate-transporter assignment was found in the reviewed sources. [Pharmacokinetic Profile and Evaluation of Acute and Subchronic Oral Toxicity of Shikimic Acid in Mice.](https://pubmed.ncbi.nlm.nih.gov/40852254/)
Complete structured claim and evidence
Ex-vivo 2 mM shikimic acid decreased ADP-induced platelet aggregation.
Shikimic acid → Human ADP-stimulated platelet aggregation with shikimic acid Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_contrast
{"intervention": "Shikimic acid at the endpoint-specific concentration", "comparator": "Matched stimulated blood without shikimic acid", "endpoint": "Ex-vivo 2 mM shikimic acid decreased ADP-induced platelet aggregation.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Blood from 22 sedentary humans, exposed ex vivo to 0.1–2 mM shikimic acid.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
No ingestion, clinical thrombosis measurement or direct receptor binding. PAC-1 is retained as an assay label, not a procaspase-targeting compound.
plain_language
Ex-vivo 2 mM shikimic acid decreased ADP-induced platelet aggregation.
primary_references
Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population. | 2016 | DOI 10.1039/c6fo00927a | PMID 27480079 | https://pubmed.ncbi.nlm.nih.gov/27480079/ | https://doi.org/10.1039/c6fo00927a
source_locator
Reviewed reference lines 55-55; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 55–55
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Blood from 22 sedentary humans, exposed ex vivo to 0.1–2 mM shikimic acid. · Recorded from source · Recorded from source
**Human blood was exposed outside the body.** Veach 2016 added 0.1–2 mM shikimic acid to blood from 22 sedentary participants. ADP-induced aggregation decreased at 2 mM, whereas collagen-induced aggregation did not significantly decrease. Flow cytometry recorded lower PAC-1 signal at 2 mM, CD62P at 1–2 mM, monocyte–platelet aggregates at 0.5–2 mM and CD31 at 1 mM. PAC-1 here is a platelet activation assay label; the abstract’s expansion as a procaspase-activating compound is not imported as a drug mechanism. This ex-vivo experiment is not an oral trial, direct P2Y12-binding assay or clinical thrombosis result. The millimolar exposures exceed the micromolar animal oral peaks cited above, without establishing any human equivalence. [Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population.](https://pubmed.ncbi.nlm.nih.gov/27480079/)
Complete structured claim and evidence
Shikimic acid did not significantly inhibit collagen-induced platelet aggregation in the tested human blood assay.
Shikimic acid → Human collagen-stimulated platelet aggregation with shikimic acid Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_contrast
{"intervention": "Shikimic acid at the endpoint-specific concentration", "comparator": "Matched stimulated blood without shikimic acid", "endpoint": "Shikimic acid did not significantly inhibit collagen-induced platelet aggregation in the tested human blood assay.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Blood from 22 sedentary humans, exposed ex vivo to 0.1–2 mM shikimic acid.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
No ingestion, clinical thrombosis measurement or direct receptor binding. PAC-1 is retained as an assay label, not a procaspase-targeting compound.
plain_language
Shikimic acid did not significantly inhibit collagen-induced platelet aggregation in the tested human blood assay.
primary_references
Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population. | 2016 | DOI 10.1039/c6fo00927a | PMID 27480079 | https://pubmed.ncbi.nlm.nih.gov/27480079/ | https://doi.org/10.1039/c6fo00927a
source_locator
Reviewed reference lines 55-55; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 55–55
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Blood from 22 sedentary humans, exposed ex vivo to 0.1–2 mM shikimic acid. · Recorded from source · Recorded from source
**Human blood was exposed outside the body.** Veach 2016 added 0.1–2 mM shikimic acid to blood from 22 sedentary participants. ADP-induced aggregation decreased at 2 mM, whereas collagen-induced aggregation did not significantly decrease. Flow cytometry recorded lower PAC-1 signal at 2 mM, CD62P at 1–2 mM, monocyte–platelet aggregates at 0.5–2 mM and CD31 at 1 mM. PAC-1 here is a platelet activation assay label; the abstract’s expansion as a procaspase-activating compound is not imported as a drug mechanism. This ex-vivo experiment is not an oral trial, direct P2Y12-binding assay or clinical thrombosis result. The millimolar exposures exceed the micromolar animal oral peaks cited above, without establishing any human equivalence. [Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population.](https://pubmed.ncbi.nlm.nih.gov/27480079/)
Complete structured claim and evidence
Ex-vivo 2 mM shikimic acid decreased the platelet PAC-1 activation signal.
Shikimic acid → Human platelet PAC-1 flow-cytometry signal Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_contrast
{"intervention": "Shikimic acid at the endpoint-specific concentration", "comparator": "Matched stimulated blood without shikimic acid", "endpoint": "Ex-vivo 2 mM shikimic acid decreased the platelet PAC-1 activation signal.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Blood from 22 sedentary humans, exposed ex vivo to 0.1–2 mM shikimic acid.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
No ingestion, clinical thrombosis measurement or direct receptor binding. PAC-1 is retained as an assay label, not a procaspase-targeting compound.
plain_language
Ex-vivo 2 mM shikimic acid decreased the platelet PAC-1 activation signal.
primary_references
Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population. | 2016 | DOI 10.1039/c6fo00927a | PMID 27480079 | https://pubmed.ncbi.nlm.nih.gov/27480079/ | https://doi.org/10.1039/c6fo00927a
source_locator
Reviewed reference lines 55-55; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 55–55
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Blood from 22 sedentary humans, exposed ex vivo to 0.1–2 mM shikimic acid. · Recorded from source · Recorded from source
**Human blood was exposed outside the body.** Veach 2016 added 0.1–2 mM shikimic acid to blood from 22 sedentary participants. ADP-induced aggregation decreased at 2 mM, whereas collagen-induced aggregation did not significantly decrease. Flow cytometry recorded lower PAC-1 signal at 2 mM, CD62P at 1–2 mM, monocyte–platelet aggregates at 0.5–2 mM and CD31 at 1 mM. PAC-1 here is a platelet activation assay label; the abstract’s expansion as a procaspase-activating compound is not imported as a drug mechanism. This ex-vivo experiment is not an oral trial, direct P2Y12-binding assay or clinical thrombosis result. The millimolar exposures exceed the micromolar animal oral peaks cited above, without establishing any human equivalence. [Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population.](https://pubmed.ncbi.nlm.nih.gov/27480079/)
Complete structured claim and evidence
Shikimic acid at 1–2 mM decreased CD62P signal in the ex-vivo assay.
Shikimic acid → Human platelet CD62P signal with shikimic acid Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_contrast
{"intervention": "Shikimic acid at the endpoint-specific concentration", "comparator": "Matched stimulated blood without shikimic acid", "endpoint": "Shikimic acid at 1–2 mM decreased CD62P signal in the ex-vivo assay.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Blood from 22 sedentary humans, exposed ex vivo to 0.1–2 mM shikimic acid.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
No ingestion, clinical thrombosis measurement or direct receptor binding. PAC-1 is retained as an assay label, not a procaspase-targeting compound.
plain_language
Shikimic acid at 1–2 mM decreased CD62P signal in the ex-vivo assay.
primary_references
Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population. | 2016 | DOI 10.1039/c6fo00927a | PMID 27480079 | https://pubmed.ncbi.nlm.nih.gov/27480079/ | https://doi.org/10.1039/c6fo00927a
source_locator
Reviewed reference lines 55-55; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 55–55
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Blood from 22 sedentary humans, exposed ex vivo to 0.1–2 mM shikimic acid. · Recorded from source · Recorded from source
**Human blood was exposed outside the body.** Veach 2016 added 0.1–2 mM shikimic acid to blood from 22 sedentary participants. ADP-induced aggregation decreased at 2 mM, whereas collagen-induced aggregation did not significantly decrease. Flow cytometry recorded lower PAC-1 signal at 2 mM, CD62P at 1–2 mM, monocyte–platelet aggregates at 0.5–2 mM and CD31 at 1 mM. PAC-1 here is a platelet activation assay label; the abstract’s expansion as a procaspase-activating compound is not imported as a drug mechanism. This ex-vivo experiment is not an oral trial, direct P2Y12-binding assay or clinical thrombosis result. The millimolar exposures exceed the micromolar animal oral peaks cited above, without establishing any human equivalence. [Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population.](https://pubmed.ncbi.nlm.nih.gov/27480079/)
Complete structured claim and evidence
Shikimic acid at 0.5–2 mM decreased monocyte–platelet aggregates.
Shikimic acid → Human monocyte–platelet aggregate formation with shikimic acid Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_contrast
{"intervention": "Shikimic acid at the endpoint-specific concentration", "comparator": "Matched stimulated blood without shikimic acid", "endpoint": "Shikimic acid at 0.5–2 mM decreased monocyte–platelet aggregates.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Blood from 22 sedentary humans, exposed ex vivo to 0.1–2 mM shikimic acid.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
No ingestion, clinical thrombosis measurement or direct receptor binding. PAC-1 is retained as an assay label, not a procaspase-targeting compound.
plain_language
Shikimic acid at 0.5–2 mM decreased monocyte–platelet aggregates.
primary_references
Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population. | 2016 | DOI 10.1039/c6fo00927a | PMID 27480079 | https://pubmed.ncbi.nlm.nih.gov/27480079/ | https://doi.org/10.1039/c6fo00927a
source_locator
Reviewed reference lines 55-55; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 55–55
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Blood from 22 sedentary humans, exposed ex vivo to 0.1–2 mM shikimic acid. · Recorded from source · Recorded from source
**Human blood was exposed outside the body.** Veach 2016 added 0.1–2 mM shikimic acid to blood from 22 sedentary participants. ADP-induced aggregation decreased at 2 mM, whereas collagen-induced aggregation did not significantly decrease. Flow cytometry recorded lower PAC-1 signal at 2 mM, CD62P at 1–2 mM, monocyte–platelet aggregates at 0.5–2 mM and CD31 at 1 mM. PAC-1 here is a platelet activation assay label; the abstract’s expansion as a procaspase-activating compound is not imported as a drug mechanism. This ex-vivo experiment is not an oral trial, direct P2Y12-binding assay or clinical thrombosis result. The millimolar exposures exceed the micromolar animal oral peaks cited above, without establishing any human equivalence. [Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population.](https://pubmed.ncbi.nlm.nih.gov/27480079/)
Complete structured claim and evidence
Shikimic acid at 1 mM decreased CD31 signal in the ex-vivo study.
Shikimic acid → Human platelet CD31 signal with shikimic acid Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_contrast
{"intervention": "Shikimic acid at the endpoint-specific concentration", "comparator": "Matched stimulated blood without shikimic acid", "endpoint": "Shikimic acid at 1 mM decreased CD31 signal in the ex-vivo study.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Blood from 22 sedentary humans, exposed ex vivo to 0.1–2 mM shikimic acid.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
No ingestion, clinical thrombosis measurement or direct receptor binding. PAC-1 is retained as an assay label, not a procaspase-targeting compound.
plain_language
Shikimic acid at 1 mM decreased CD31 signal in the ex-vivo study.
primary_references
Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population. | 2016 | DOI 10.1039/c6fo00927a | PMID 27480079 | https://pubmed.ncbi.nlm.nih.gov/27480079/ | https://doi.org/10.1039/c6fo00927a
source_locator
Reviewed reference lines 55-55; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 55–55
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Blood from 22 sedentary humans, exposed ex vivo to 0.1–2 mM shikimic acid. · Recorded from source · Recorded from source
**Human blood was exposed outside the body.** Veach 2016 added 0.1–2 mM shikimic acid to blood from 22 sedentary participants. ADP-induced aggregation decreased at 2 mM, whereas collagen-induced aggregation did not significantly decrease. Flow cytometry recorded lower PAC-1 signal at 2 mM, CD62P at 1–2 mM, monocyte–platelet aggregates at 0.5–2 mM and CD31 at 1 mM. PAC-1 here is a platelet activation assay label; the abstract’s expansion as a procaspase-activating compound is not imported as a drug mechanism. This ex-vivo experiment is not an oral trial, direct P2Y12-binding assay or clinical thrombosis result. The millimolar exposures exceed the micromolar animal oral peaks cited above, without establishing any human equivalence. [Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population.](https://pubmed.ncbi.nlm.nih.gov/27480079/)
Complete structured claim and evidence
TSA showed the recorded decrease in Rat TSA-stimulated platelet aggregation.
Triacetylshikimic acid / TSA → Rat TSA-stimulated platelet aggregation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Triacetylshikimic acid rat experiments; indexed abstract.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Derivative-specific result. Unextracted dose/time remain unspecified; no transfer to shikimic acid.
plain_language
TSA showed the recorded decrease in Rat TSA-stimulated platelet aggregation.
primary_references
Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid. | 2016 | DOI 10.3109/13880209.2016.1153663 | PMID 27609150 | https://pubmed.ncbi.nlm.nih.gov/27609150/ | https://doi.org/10.3109/13880209.2016.1153663
primary_references
Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats. | 2002 | DOI 10.1097/00005344-200202000-00013 | PMID 11791012 | https://pubmed.ncbi.nlm.nih.gov/11791012/ | https://doi.org/10.1097/00005344-200202000-00013
primary_references
Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats. | 2012 | DOI 10.1007/s10620-012-2155-y | PMID 22476587 | https://pubmed.ncbi.nlm.nih.gov/22476587/ | https://doi.org/10.1007/s10620-012-2155-y
source_locator
Reviewed reference lines 57-57; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 57–57
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Triacetylshikimic acid rat experiments; indexed abstract. · Recorded from source · Recorded from source
**Derivatives keep their own outcomes.** Triacetylshikimic acid (TSA) reduced stimulated platelet aggregation and shunt thrombosis in rat experiments; reported cAMP increased, while cGMP, thromboxane/prostacyclin metabolites and clotting-time endpoints included null results. Those results are not assigned to parent shikimic acid. The separately tested 3,4-O-isopropylidene derivative (ISA) has rodent inflammatory/pain studies and cell-free radical-scavenging assays. Structural similarity does not establish interchangeable pharmacokinetics, targets or safety. [Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats.](https://pubmed.ncbi.nlm.nih.gov/11791012/) [Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats.](https://pubmed.ncbi.nlm.nih.gov/22476587/) [Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid.](https://pubmed.ncbi.nlm.nih.gov/27609150/)
Complete structured claim and evidence
TSA showed the recorded increase in Rat TSA-associated platelet cAMP.
Triacetylshikimic acid / TSA → Rat TSA-associated platelet cAMP Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Triacetylshikimic acid rat experiments; indexed abstract.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Derivative-specific result. Unextracted dose/time remain unspecified; no transfer to shikimic acid.
plain_language
TSA showed the recorded increase in Rat TSA-associated platelet cAMP.
primary_references
Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid. | 2016 | DOI 10.3109/13880209.2016.1153663 | PMID 27609150 | https://pubmed.ncbi.nlm.nih.gov/27609150/ | https://doi.org/10.3109/13880209.2016.1153663
primary_references
Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats. | 2002 | DOI 10.1097/00005344-200202000-00013 | PMID 11791012 | https://pubmed.ncbi.nlm.nih.gov/11791012/ | https://doi.org/10.1097/00005344-200202000-00013
primary_references
Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats. | 2012 | DOI 10.1007/s10620-012-2155-y | PMID 22476587 | https://pubmed.ncbi.nlm.nih.gov/22476587/ | https://doi.org/10.1007/s10620-012-2155-y
source_locator
Reviewed reference lines 57-57; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 57–57
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Triacetylshikimic acid rat experiments; indexed abstract. · Recorded from source · Recorded from source
**Derivatives keep their own outcomes.** Triacetylshikimic acid (TSA) reduced stimulated platelet aggregation and shunt thrombosis in rat experiments; reported cAMP increased, while cGMP, thromboxane/prostacyclin metabolites and clotting-time endpoints included null results. Those results are not assigned to parent shikimic acid. The separately tested 3,4-O-isopropylidene derivative (ISA) has rodent inflammatory/pain studies and cell-free radical-scavenging assays. Structural similarity does not establish interchangeable pharmacokinetics, targets or safety. [Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats.](https://pubmed.ncbi.nlm.nih.gov/11791012/) [Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats.](https://pubmed.ncbi.nlm.nih.gov/22476587/) [Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid.](https://pubmed.ncbi.nlm.nih.gov/27609150/)
Complete structured claim and evidence
TSA showed the recorded no detected change in Rat TSA-associated platelet cGMP.
Triacetylshikimic acid / TSA → Rat TSA-associated platelet cGMP Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Triacetylshikimic acid rat experiments; indexed abstract.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Derivative-specific result. Unextracted dose/time remain unspecified; no transfer to shikimic acid.
plain_language
TSA showed the recorded no detected change in Rat TSA-associated platelet cGMP.
primary_references
Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid. | 2016 | DOI 10.3109/13880209.2016.1153663 | PMID 27609150 | https://pubmed.ncbi.nlm.nih.gov/27609150/ | https://doi.org/10.3109/13880209.2016.1153663
primary_references
Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats. | 2002 | DOI 10.1097/00005344-200202000-00013 | PMID 11791012 | https://pubmed.ncbi.nlm.nih.gov/11791012/ | https://doi.org/10.1097/00005344-200202000-00013
primary_references
Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats. | 2012 | DOI 10.1007/s10620-012-2155-y | PMID 22476587 | https://pubmed.ncbi.nlm.nih.gov/22476587/ | https://doi.org/10.1007/s10620-012-2155-y
source_locator
Reviewed reference lines 57-57; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 57–57
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Triacetylshikimic acid rat experiments; indexed abstract. · Recorded from source · Recorded from source
**Derivatives keep their own outcomes.** Triacetylshikimic acid (TSA) reduced stimulated platelet aggregation and shunt thrombosis in rat experiments; reported cAMP increased, while cGMP, thromboxane/prostacyclin metabolites and clotting-time endpoints included null results. Those results are not assigned to parent shikimic acid. The separately tested 3,4-O-isopropylidene derivative (ISA) has rodent inflammatory/pain studies and cell-free radical-scavenging assays. Structural similarity does not establish interchangeable pharmacokinetics, targets or safety. [Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats.](https://pubmed.ncbi.nlm.nih.gov/11791012/) [Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats.](https://pubmed.ncbi.nlm.nih.gov/22476587/) [Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid.](https://pubmed.ncbi.nlm.nih.gov/27609150/)
Complete structured claim and evidence
TSA showed the recorded no detected change in Rat clotting-time endpoints with TSA.
Triacetylshikimic acid / TSA → Rat clotting-time endpoints with TSA Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Triacetylshikimic acid rat experiments; indexed abstract.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Derivative-specific result. Unextracted dose/time remain unspecified; no transfer to shikimic acid.
plain_language
TSA showed the recorded no detected change in Rat clotting-time endpoints with TSA.
primary_references
Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid. | 2016 | DOI 10.3109/13880209.2016.1153663 | PMID 27609150 | https://pubmed.ncbi.nlm.nih.gov/27609150/ | https://doi.org/10.3109/13880209.2016.1153663
primary_references
Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats. | 2002 | DOI 10.1097/00005344-200202000-00013 | PMID 11791012 | https://pubmed.ncbi.nlm.nih.gov/11791012/ | https://doi.org/10.1097/00005344-200202000-00013
primary_references
Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats. | 2012 | DOI 10.1007/s10620-012-2155-y | PMID 22476587 | https://pubmed.ncbi.nlm.nih.gov/22476587/ | https://doi.org/10.1007/s10620-012-2155-y
source_locator
Reviewed reference lines 57-57; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 57–57
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Triacetylshikimic acid rat experiments; indexed abstract. · Recorded from source · Recorded from source
**Derivatives keep their own outcomes.** Triacetylshikimic acid (TSA) reduced stimulated platelet aggregation and shunt thrombosis in rat experiments; reported cAMP increased, while cGMP, thromboxane/prostacyclin metabolites and clotting-time endpoints included null results. Those results are not assigned to parent shikimic acid. The separately tested 3,4-O-isopropylidene derivative (ISA) has rodent inflammatory/pain studies and cell-free radical-scavenging assays. Structural similarity does not establish interchangeable pharmacokinetics, targets or safety. [Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats.](https://pubmed.ncbi.nlm.nih.gov/11791012/) [Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats.](https://pubmed.ncbi.nlm.nih.gov/22476587/) [Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid.](https://pubmed.ncbi.nlm.nih.gov/27609150/)
Complete structured claim and evidence
Shikimic acid lowered the LPS-associated nitrite readout.
Shikimic acid → Mouse BV2 nitrite release Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "Shikimic acid in the endpoint-specific assay", "comparator": "Matched assay without shikimic acid", "endpoint": "Shikimic acid lowered the LPS-associated nitrite readout.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2 cells; 5/10 µM SA, LPS 1 µg/mL, 24 h for inflammatory endpoints; separate viability test.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Assay-specific redox or viability signal; not a unique ROS identity or direct scavenging mechanism.
plain_language
Shikimic acid lowered the LPS-associated nitrite readout.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 59-59; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 59–59
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2 cells; 5/10 µM SA, LPS 1 µg/mL, 24 h for inflammatory endpoints; separate viability test. · Recorded from source · Recorded from source
**Microglial redox responses were measured at micromolar exposure.** In mouse BV2 cells, 5 or 10 µM shikimic acid with 1 µg/mL LPS for 24 h decreased nitrite and DCFH-DA oxidation readouts; concentrations up to 10 µM did not significantly reduce the reported CCK8 viability signal. These are assays of inflammatory/redox response and metabolic viability, not measurements of a unique reactive-oxygen species or proof of direct radical scavenging. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Shikimic acid lowered LPS-associated DCFH oxidation.
Shikimic acid → Mouse BV2 DCFH-DA oxidation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "Shikimic acid in the endpoint-specific assay", "comparator": "Matched assay without shikimic acid", "endpoint": "Shikimic acid lowered LPS-associated DCFH oxidation.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2 cells; 5/10 µM SA, LPS 1 µg/mL, 24 h for inflammatory endpoints; separate viability test.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Assay-specific redox or viability signal; not a unique ROS identity or direct scavenging mechanism.
plain_language
Shikimic acid lowered LPS-associated DCFH oxidation.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 59-59; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 59–59
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2 cells; 5/10 µM SA, LPS 1 µg/mL, 24 h for inflammatory endpoints; separate viability test. · Recorded from source · Recorded from source
**Microglial redox responses were measured at micromolar exposure.** In mouse BV2 cells, 5 or 10 µM shikimic acid with 1 µg/mL LPS for 24 h decreased nitrite and DCFH-DA oxidation readouts; concentrations up to 10 µM did not significantly reduce the reported CCK8 viability signal. These are assays of inflammatory/redox response and metabolic viability, not measurements of a unique reactive-oxygen species or proof of direct radical scavenging. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Shikimic acid up to 10 micromolar did not significantly reduce CCK8 signal.
Shikimic acid → Mouse BV2 CCK8 viability signal Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "Shikimic acid in the endpoint-specific assay", "comparator": "Matched assay without shikimic acid", "endpoint": "Shikimic acid up to 10 micromolar did not significantly reduce CCK8 signal.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2 cells; 5/10 µM SA, LPS 1 µg/mL, 24 h for inflammatory endpoints; separate viability test.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Assay-specific redox or viability signal; not a unique ROS identity or direct scavenging mechanism.
plain_language
Shikimic acid up to 10 micromolar did not significantly reduce CCK8 signal.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 59-59; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 59–59
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2 cells; 5/10 µM SA, LPS 1 µg/mL, 24 h for inflammatory endpoints; separate viability test. · Recorded from source · Recorded from source
**Microglial redox responses were measured at micromolar exposure.** In mouse BV2 cells, 5 or 10 µM shikimic acid with 1 µg/mL LPS for 24 h decreased nitrite and DCFH-DA oxidation readouts; concentrations up to 10 µM did not significantly reduce the reported CCK8 viability signal. These are assays of inflammatory/redox response and metabolic viability, not measurements of a unique reactive-oxygen species or proof of direct radical scavenging. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Shikimic acid increased AKT phosphorylation in BV2 cells.
Shikimic acid → Mouse BV2 AKT phosphorylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "Shikimic acid", "comparator": "Matched cells without SA", "endpoint": "Shikimic acid increased AKT phosphorylation in BV2 cells.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2 signaling time-course.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Pathway response is not direct ligand binding or clinical efficacy.
plain_language
Shikimic acid increased AKT phosphorylation in BV2 cells.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 61-61; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 61–61
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2 signaling time-course. · Recorded from source · Recorded from source
**AKT and Nrf2 involvement does not identify the binding target.** BV2 experiments recorded increased AKT phosphorylation and nuclear Nrf2. MK2206 pretreatment attenuated Nrf2 activation and partially reversed redox/nitrite responses. A reagent labeled RA also attenuated the Nrf2 response; its identity and selectivity are not independently resolved here, so no vitamin-A or retinoic-acid interaction is created from that abbreviation. Pharmacological perturbation supports pathway involvement while leaving the initiating target and off-target alternatives open. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Shikimic acid increased nuclear Nrf2 accumulation in BV2 cells.
Shikimic acid → Mouse BV2 nuclear Nrf2 accumulation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "Shikimic acid", "comparator": "Matched cells without SA", "endpoint": "Shikimic acid increased nuclear Nrf2 accumulation in BV2 cells.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2 signaling time-course.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Pathway response is not direct ligand binding or clinical efficacy.
plain_language
Shikimic acid increased nuclear Nrf2 accumulation in BV2 cells.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 61-61; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 61–61
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2 signaling time-course. · Recorded from source · Recorded from source
**AKT and Nrf2 involvement does not identify the binding target.** BV2 experiments recorded increased AKT phosphorylation and nuclear Nrf2. MK2206 pretreatment attenuated Nrf2 activation and partially reversed redox/nitrite responses. A reagent labeled RA also attenuated the Nrf2 response; its identity and selectivity are not independently resolved here, so no vitamin-A or retinoic-acid interaction is created from that abbreviation. Pharmacological perturbation supports pathway involvement while leaving the initiating target and off-target alternatives open. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
MK2206 attenuated shikimic-acid-associated Nrf2 accumulation.
MK2206 → Mouse BV2 nuclear Nrf2 accumulation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
Shikimic acid without MK2206 present · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
Shikimic acid without MK2206 pretreatment · MK2206 Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "MK2206 pretreatment with shikimic acid", "comparator": "Shikimic acid without MK2206", "endpoint": "MK2206 attenuated shikimic-acid-associated Nrf2 accumulation.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "mk2206", "state": "pretreatment"}, {"entity_slug": "shikimic-acid", "state": "present"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2; MK2206 10 µM for 4 h before pathway assay.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Pharmacological pathway perturbation; not proof of direct SA–AKT binding or perfect inhibitor specificity.
plain_language
MK2206 attenuated shikimic-acid-associated Nrf2 accumulation.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 61-61; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 61–61
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2; MK2206 10 µM for 4 h before pathway assay. · Recorded from source · Recorded from source
**AKT and Nrf2 involvement does not identify the binding target.** BV2 experiments recorded increased AKT phosphorylation and nuclear Nrf2. MK2206 pretreatment attenuated Nrf2 activation and partially reversed redox/nitrite responses. A reagent labeled RA also attenuated the Nrf2 response; its identity and selectivity are not independently resolved here, so no vitamin-A or retinoic-acid interaction is created from that abbreviation. Pharmacological perturbation supports pathway involvement while leaving the initiating target and off-target alternatives open. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Shikimic acid reduced the LPS-associated transcript readout for mouse-il6 in BV2 cells.
Shikimic acid → Mouse interleukin-6 / Il6 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
LPS without SA added · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
LPS without SA stimulus · Lipopolysaccharide Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SA plus LPS", "comparator": "LPS without SA", "endpoint": "Shikimic acid reduced the LPS-associated transcript readout for mouse-il6 in BV2 cells.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "shikimic-acid", "state": "added"}, {"entity_slug": "lipopolysaccharide", "state": "stimulus"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Expression or secretion endpoint; not direct enzyme catalytic inhibition, binding or a human response.
plain_language
Shikimic acid reduced the LPS-associated transcript readout for mouse-il6 in BV2 cells.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 63-63; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 63–63
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h. · Recorded from source · Recorded from source
**Inflammatory expression and phosphorylation are distinct endpoints.** In the same BV2/LPS model, shikimic acid reduced Il6, Tnf, Nos2 and Ptgs2 transcripts at 12 h; protein/secretion measurements at 24 h also decreased. At 1 h, p65 and IκB phosphorylation decreased and IκB degradation was reduced. These changes do not establish direct inhibition of COX-2 catalysis or direct binding to every signaling protein. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Shikimic acid reduced the LPS-associated protein readout for mouse-il6 in BV2 cells.
Shikimic acid → Mouse interleukin-6 / Il6 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
LPS without SA added · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
LPS without SA stimulus · Lipopolysaccharide Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SA plus LPS", "comparator": "LPS without SA", "endpoint": "Shikimic acid reduced the LPS-associated protein readout for mouse-il6 in BV2 cells.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "shikimic-acid", "state": "added"}, {"entity_slug": "lipopolysaccharide", "state": "stimulus"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Expression or secretion endpoint; not direct enzyme catalytic inhibition, binding or a human response.
plain_language
Shikimic acid reduced the LPS-associated protein readout for mouse-il6 in BV2 cells.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 63-63; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 63–63
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h. · Recorded from source · Recorded from source
**Inflammatory expression and phosphorylation are distinct endpoints.** In the same BV2/LPS model, shikimic acid reduced Il6, Tnf, Nos2 and Ptgs2 transcripts at 12 h; protein/secretion measurements at 24 h also decreased. At 1 h, p65 and IκB phosphorylation decreased and IκB degradation was reduced. These changes do not establish direct inhibition of COX-2 catalysis or direct binding to every signaling protein. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Shikimic acid reduced the LPS-associated transcript readout for mouse-tnf in BV2 cells.
Shikimic acid → Mouse tumor necrosis factor / Tnf Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
LPS without SA added · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
LPS without SA stimulus · Lipopolysaccharide Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SA plus LPS", "comparator": "LPS without SA", "endpoint": "Shikimic acid reduced the LPS-associated transcript readout for mouse-tnf in BV2 cells.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "shikimic-acid", "state": "added"}, {"entity_slug": "lipopolysaccharide", "state": "stimulus"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Expression or secretion endpoint; not direct enzyme catalytic inhibition, binding or a human response.
plain_language
Shikimic acid reduced the LPS-associated transcript readout for mouse-tnf in BV2 cells.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 63-63; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 63–63
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h. · Recorded from source · Recorded from source
**Inflammatory expression and phosphorylation are distinct endpoints.** In the same BV2/LPS model, shikimic acid reduced Il6, Tnf, Nos2 and Ptgs2 transcripts at 12 h; protein/secretion measurements at 24 h also decreased. At 1 h, p65 and IκB phosphorylation decreased and IκB degradation was reduced. These changes do not establish direct inhibition of COX-2 catalysis or direct binding to every signaling protein. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Shikimic acid reduced the LPS-associated protein readout for mouse-tnf in BV2 cells.
Shikimic acid → Mouse tumor necrosis factor / Tnf Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
LPS without SA added · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
LPS without SA stimulus · Lipopolysaccharide Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SA plus LPS", "comparator": "LPS without SA", "endpoint": "Shikimic acid reduced the LPS-associated protein readout for mouse-tnf in BV2 cells.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "shikimic-acid", "state": "added"}, {"entity_slug": "lipopolysaccharide", "state": "stimulus"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Expression or secretion endpoint; not direct enzyme catalytic inhibition, binding or a human response.
plain_language
Shikimic acid reduced the LPS-associated protein readout for mouse-tnf in BV2 cells.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 63-63; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 63–63
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h. · Recorded from source · Recorded from source
**Inflammatory expression and phosphorylation are distinct endpoints.** In the same BV2/LPS model, shikimic acid reduced Il6, Tnf, Nos2 and Ptgs2 transcripts at 12 h; protein/secretion measurements at 24 h also decreased. At 1 h, p65 and IκB phosphorylation decreased and IκB degradation was reduced. These changes do not establish direct inhibition of COX-2 catalysis or direct binding to every signaling protein. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Shikimic acid reduced the LPS-associated transcript readout for mouse-nos2 in BV2 cells.
Shikimic acid → Mouse inducible nitric oxide synthase / Nos2 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
LPS without SA added · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
LPS without SA stimulus · Lipopolysaccharide Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SA plus LPS", "comparator": "LPS without SA", "endpoint": "Shikimic acid reduced the LPS-associated transcript readout for mouse-nos2 in BV2 cells.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "shikimic-acid", "state": "added"}, {"entity_slug": "lipopolysaccharide", "state": "stimulus"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Expression or secretion endpoint; not direct enzyme catalytic inhibition, binding or a human response.
plain_language
Shikimic acid reduced the LPS-associated transcript readout for mouse-nos2 in BV2 cells.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 63-63; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 63–63
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h. · Recorded from source · Recorded from source
**Inflammatory expression and phosphorylation are distinct endpoints.** In the same BV2/LPS model, shikimic acid reduced Il6, Tnf, Nos2 and Ptgs2 transcripts at 12 h; protein/secretion measurements at 24 h also decreased. At 1 h, p65 and IκB phosphorylation decreased and IκB degradation was reduced. These changes do not establish direct inhibition of COX-2 catalysis or direct binding to every signaling protein. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Shikimic acid reduced the LPS-associated protein readout for mouse-nos2 in BV2 cells.
Shikimic acid → Mouse inducible nitric oxide synthase / Nos2 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
LPS without SA added · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
LPS without SA stimulus · Lipopolysaccharide Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SA plus LPS", "comparator": "LPS without SA", "endpoint": "Shikimic acid reduced the LPS-associated protein readout for mouse-nos2 in BV2 cells.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "shikimic-acid", "state": "added"}, {"entity_slug": "lipopolysaccharide", "state": "stimulus"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Expression or secretion endpoint; not direct enzyme catalytic inhibition, binding or a human response.
plain_language
Shikimic acid reduced the LPS-associated protein readout for mouse-nos2 in BV2 cells.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 63-63; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 63–63
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h. · Recorded from source · Recorded from source
**Inflammatory expression and phosphorylation are distinct endpoints.** In the same BV2/LPS model, shikimic acid reduced Il6, Tnf, Nos2 and Ptgs2 transcripts at 12 h; protein/secretion measurements at 24 h also decreased. At 1 h, p65 and IκB phosphorylation decreased and IκB degradation was reduced. These changes do not establish direct inhibition of COX-2 catalysis or direct binding to every signaling protein. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Shikimic acid reduced the LPS-associated transcript readout for mouse-ptgs2 in BV2 cells.
Shikimic acid → Mouse cyclooxygenase-2 / Ptgs2 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
LPS without SA added · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
LPS without SA stimulus · Lipopolysaccharide Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SA plus LPS", "comparator": "LPS without SA", "endpoint": "Shikimic acid reduced the LPS-associated transcript readout for mouse-ptgs2 in BV2 cells.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "shikimic-acid", "state": "added"}, {"entity_slug": "lipopolysaccharide", "state": "stimulus"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Expression or secretion endpoint; not direct enzyme catalytic inhibition, binding or a human response.
plain_language
Shikimic acid reduced the LPS-associated transcript readout for mouse-ptgs2 in BV2 cells.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 63-63; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 63–63
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h. · Recorded from source · Recorded from source
**Inflammatory expression and phosphorylation are distinct endpoints.** In the same BV2/LPS model, shikimic acid reduced Il6, Tnf, Nos2 and Ptgs2 transcripts at 12 h; protein/secretion measurements at 24 h also decreased. At 1 h, p65 and IκB phosphorylation decreased and IκB degradation was reduced. These changes do not establish direct inhibition of COX-2 catalysis or direct binding to every signaling protein. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Shikimic acid reduced the LPS-associated protein readout for mouse-ptgs2 in BV2 cells.
Shikimic acid → Mouse cyclooxygenase-2 / Ptgs2 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
LPS without SA added · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
LPS without SA stimulus · Lipopolysaccharide Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SA plus LPS", "comparator": "LPS without SA", "endpoint": "Shikimic acid reduced the LPS-associated protein readout for mouse-ptgs2 in BV2 cells.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "shikimic-acid", "state": "added"}, {"entity_slug": "lipopolysaccharide", "state": "stimulus"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Expression or secretion endpoint; not direct enzyme catalytic inhibition, binding or a human response.
plain_language
Shikimic acid reduced the LPS-associated protein readout for mouse-ptgs2 in BV2 cells.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 63-63; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 63–63
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2: 5/10 µM SA plus LPS 1 µg/mL; transcript at 12 h, protein/secretion at 24 h. · Recorded from source · Recorded from source
**Inflammatory expression and phosphorylation are distinct endpoints.** In the same BV2/LPS model, shikimic acid reduced Il6, Tnf, Nos2 and Ptgs2 transcripts at 12 h; protein/secretion measurements at 24 h also decreased. At 1 h, p65 and IκB phosphorylation decreased and IκB degradation was reduced. These changes do not establish direct inhibition of COX-2 catalysis or direct binding to every signaling protein. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
SA reduced p65 and IκB phosphorylation under LPS challenge.
Shikimic acid → Mouse BV2 p65/IκB phosphorylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
LPS alone added · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
LPS alone stimulus · Lipopolysaccharide Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SA plus LPS", "comparator": "LPS alone", "endpoint": "SA reduced p65 and IκB phosphorylation under LPS challenge.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "shikimic-acid", "state": "added"}, {"entity_slug": "lipopolysaccharide", "state": "stimulus"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse BV2; 10 µM SA, LPS 1 µg/mL, 1 h.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
SA reduced p65 and IκB phosphorylation under LPS challenge.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 63-63; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 63–63
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse BV2; 10 µM SA, LPS 1 µg/mL, 1 h. · Recorded from source · Recorded from source
**Inflammatory expression and phosphorylation are distinct endpoints.** In the same BV2/LPS model, shikimic acid reduced Il6, Tnf, Nos2 and Ptgs2 transcripts at 12 h; protein/secretion measurements at 24 h also decreased. At 1 h, p65 and IκB phosphorylation decreased and IκB degradation was reduced. These changes do not establish direct inhibition of COX-2 catalysis or direct binding to every signaling protein. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
Injected SA preserved TH-associated measurements after intranigral LPS.
Shikimic acid → Mouse TH-associated measures after intranigral LPS Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
LPS challenge without SA injected · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
LPS challenge without SA prior model challenge · Lipopolysaccharide Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SA after LPS challenge", "comparator": "LPS challenge without SA", "endpoint": "Injected SA preserved TH-associated measurements after intranigral LPS.", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "shikimic-acid", "state": "injected"}, {"entity_slug": "lipopolysaccharide", "state": "prior model challenge"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse; SA 100 mg/kg intraperitoneal daily for four weeks.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Inflammatory mouse model, not human Parkinson disease treatment or measured oral brain target engagement.
plain_language
Injected SA preserved TH-associated measurements after intranigral LPS.
primary_references
Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/
source_locator
Reviewed reference lines 65-65; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 65–65
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse; SA 100 mg/kg intraperitoneal daily for four weeks. · Recorded from source · Recorded from source
**The neuroinflammation experiment used injected treatment.** After intranigral LPS challenge, mice receiving shikimic acid 100 mg/kg intraperitoneally daily for four weeks showed improved motor-related readouts and preservation of TH-associated measures, with lower microglial markers. This is an inflammatory mouse model; human Parkinson disease efficacy, oral brain exposure and a specific molecular target were not established. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)
Complete structured claim and evidence
SA reduced nitrite and selected cytokine responses in LPS-challenged RAW264.7 cells.
Shikimic acid → Mouse RAW264.7 LPS-induced cytokine/nitrite response Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_condition
LPS without SA added · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
LPS without SA stimulus · Lipopolysaccharide Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SA plus LPS", "comparator": "LPS without SA", "endpoint": "SA reduced nitrite and selected cytokine responses in LPS-challenged RAW264.7 cells.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "shikimic-acid", "state": "added"}, {"entity_slug": "lipopolysaccharide", "state": "stimulus"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse RAW264.7; accessible abstract, cell dose not independently extracted.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
SA reduced nitrite and selected cytokine responses in LPS-challenged RAW264.7 cells.
primary_references
Shikimic acid inhibits LPS-induced cellular pro-inflammatory cytokines and attenuates mechanical hyperalgesia in mice. | 2016 | DOI 10.1016/j.intimp.2016.07.016 | PMID 27454847 | https://pubmed.ncbi.nlm.nih.gov/27454847/ | https://doi.org/10.1016/j.intimp.2016.07.016
source_locator
Reviewed reference lines 67-67; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 67–67
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse RAW264.7; accessible abstract, cell dose not independently extracted. · Recorded from source · Recorded from source
**Other inflammatory models are separate evidence.** Rabelo 2016 reported lower nitrite, TNF and IL-1β responses and reduced ERK/p38 phosphorylation in LPS-exposed mouse RAW264.7 macrophages. Rodent pain outcomes were also reported at 50–200 mg/kg depending on the test. Only the indexed abstract was available for this extraction, so unverified route, cell dose and timing are not invented. Lower p38 signaling here and higher p38 phosphorylation in hair cells are different conditions, not automatically conflicting studies. [Shikimic acid inhibits LPS-induced cellular pro-inflammatory cytokines and attenuates mechanical hyperalgesia in mice.](https://pubmed.ncbi.nlm.nih.gov/27454847/)
Complete structured claim and evidence
SA increased MBP-associated OPC differentiation after 72 hours.
Shikimic acid → Rat myelin basic protein / Mbp Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "Shikimic acid", "comparator": "Vehicle", "endpoint": "SA increased MBP-associated OPC differentiation after 72 hours.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Primary rat OPCs, 1–100 µg/mL; 100 µg/mL (about 574 µM) used for follow-up.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Differentiation marker, not all-cell proliferation or human therapeutic exposure.
plain_language
SA increased MBP-associated OPC differentiation after 72 hours.
primary_references
Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/
source_locator
Reviewed reference lines 69-69; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 69–69
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Primary rat OPCs, 1–100 µg/mL; 100 µg/mL (about 574 µM) used for follow-up. · Recorded from source · Recorded from source
**Oligodendrocyte differentiation differs from proliferation.** In primary rat oligodendrocyte precursor cultures, shikimic acid at 1–100 µg/mL increased MBP-associated differentiation after 72 h, with 100 µg/mL used for subsequent experiments. That highest concentration is calculated as about 574 µM. BrdU incorporation and TUNEL readouts did not significantly change. Increased MBP and fewer NG2-positive cells therefore support maturation in this model, not universal stimulation of cell proliferation. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)
Complete structured claim and evidence
SA did not significantly change the rat-opc-brdu readout.
Shikimic acid → Rat OPC BrdU incorporation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA 100 µg/mL", "comparator": "Vehicle", "endpoint": "SA did not significantly change the rat-opc-brdu readout.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Primary rat OPCs, 100 µg/mL SA versus vehicle.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
SA did not significantly change the rat-opc-brdu readout.
primary_references
Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/
source_locator
Reviewed reference lines 69-69; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 69–69
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Primary rat OPCs, 100 µg/mL SA versus vehicle. · Recorded from source · Recorded from source
**Oligodendrocyte differentiation differs from proliferation.** In primary rat oligodendrocyte precursor cultures, shikimic acid at 1–100 µg/mL increased MBP-associated differentiation after 72 h, with 100 µg/mL used for subsequent experiments. That highest concentration is calculated as about 574 µM. BrdU incorporation and TUNEL readouts did not significantly change. Increased MBP and fewer NG2-positive cells therefore support maturation in this model, not universal stimulation of cell proliferation. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)
Complete structured claim and evidence
SA did not significantly change the rat-opc-tunel readout.
Shikimic acid → Rat OPC TUNEL labeling Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA 100 µg/mL", "comparator": "Vehicle", "endpoint": "SA did not significantly change the rat-opc-tunel readout.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Primary rat OPCs, 100 µg/mL SA versus vehicle.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
SA did not significantly change the rat-opc-tunel readout.
primary_references
Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/
source_locator
Reviewed reference lines 69-69; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 69–69
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Primary rat OPCs, 100 µg/mL SA versus vehicle. · Recorded from source · Recorded from source
**Oligodendrocyte differentiation differs from proliferation.** In primary rat oligodendrocyte precursor cultures, shikimic acid at 1–100 µg/mL increased MBP-associated differentiation after 72 h, with 100 µg/mL used for subsequent experiments. That highest concentration is calculated as about 574 µM. BrdU incorporation and TUNEL readouts did not significantly change. Increased MBP and fewer NG2-positive cells therefore support maturation in this model, not universal stimulation of cell proliferation. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)
Complete structured claim and evidence
Rapamycin blocked the SA-associated MBP increase.
Rapamycin / sirolimus → Rat myelin basic protein / Mbp Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
SA without the inhibitor present · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
SA without the inhibitor present · Rapamycin / sirolimus Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "rapamycin plus SA", "comparator": "SA without the inhibitor", "endpoint": "Rapamycin blocked the SA-associated MBP increase.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "rapamycin", "state": "present"}, {"entity_slug": "shikimic-acid", "state": "present"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Primary rat OPC joint exposure, 100 µg/mL SA.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Persistence with U0126 is not a blanket null for MEK activity. Inhibitors do not identify the direct SA target.
plain_language
Rapamycin blocked the SA-associated MBP increase.
primary_references
Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/
source_locator
Reviewed reference lines 71-71; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 71–71
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Primary rat OPC joint exposure, 100 µg/mL SA. · Recorded from source · Recorded from source
**Perturbations expose a conditional signaling route.** In those rat precursor cultures, rapamycin blocked the shikimic-acid-associated rise in MBP, while the MEK inhibitor U0126 did not abolish it. PI3K inhibitors wortmannin and LY294002 reduced the elevated mTOR-phosphorylation readout toward control. These are joint experimental contrasts supporting pathway dependence; they do not establish that shikimic acid binds mTOR or that all MEK activity is irrelevant. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)
Complete structured claim and evidence
The SA-associated MBP increase persisted in the presence of U0126.
U0126 MEK-pathway inhibitor → Rat myelin basic protein / Mbp Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
SA without the inhibitor present · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
SA without the inhibitor present · U0126 MEK-pathway inhibitor Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "u0126 plus SA", "comparator": "SA without the inhibitor", "endpoint": "The SA-associated MBP increase persisted in the presence of U0126.", "effect_direction": "not_reported", "combination": "joint", "conditions": [{"entity_slug": "u0126", "state": "present"}, {"entity_slug": "shikimic-acid", "state": "present"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Primary rat OPC joint exposure, 100 µg/mL SA.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Persistence with U0126 is not a blanket null for MEK activity. Inhibitors do not identify the direct SA target.
plain_language
The SA-associated MBP increase persisted in the presence of U0126.
primary_references
Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/
source_locator
Reviewed reference lines 71-71; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 71–71
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Primary rat OPC joint exposure, 100 µg/mL SA. · Recorded from source · Recorded from source
**Perturbations expose a conditional signaling route.** In those rat precursor cultures, rapamycin blocked the shikimic-acid-associated rise in MBP, while the MEK inhibitor U0126 did not abolish it. PI3K inhibitors wortmannin and LY294002 reduced the elevated mTOR-phosphorylation readout toward control. These are joint experimental contrasts supporting pathway dependence; they do not establish that shikimic acid binds mTOR or that all MEK activity is irrelevant. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)
Complete structured claim and evidence
SA increased mTOR phosphorylation in cultured rat OPCs.
Shikimic acid → Rat OPC mTOR phosphorylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA 100 µg/mL", "comparator": "Vehicle", "endpoint": "SA increased mTOR phosphorylation in cultured rat OPCs.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Primary rat OPC signaling assay.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
SA increased mTOR phosphorylation in cultured rat OPCs.
primary_references
Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/
source_locator
Reviewed reference lines 71-71; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 71–71
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Primary rat OPC signaling assay. · Recorded from source · Recorded from source
**Perturbations expose a conditional signaling route.** In those rat precursor cultures, rapamycin blocked the shikimic-acid-associated rise in MBP, while the MEK inhibitor U0126 did not abolish it. PI3K inhibitors wortmannin and LY294002 reduced the elevated mTOR-phosphorylation readout toward control. These are joint experimental contrasts supporting pathway dependence; they do not establish that shikimic acid binds mTOR or that all MEK activity is irrelevant. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)
Complete structured claim and evidence
The PI3K inhibitor wortmannin reduced the SA-associated mTOR phosphorylation increase.
Wortmannin → Rat OPC mTOR phosphorylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
SA without the inhibitor present · Wortmannin Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
SA without the inhibitor present · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "wortmannin plus SA", "comparator": "SA without the inhibitor", "endpoint": "The PI3K inhibitor wortmannin reduced the SA-associated mTOR phosphorylation increase.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "wortmannin", "state": "present"}, {"entity_slug": "shikimic-acid", "state": "present"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Primary rat OPC joint pharmacological perturbation.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
The PI3K inhibitor wortmannin reduced the SA-associated mTOR phosphorylation increase.
primary_references
Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/
source_locator
Reviewed reference lines 71-71; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 71–71
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Primary rat OPC joint pharmacological perturbation. · Recorded from source · Recorded from source
**Perturbations expose a conditional signaling route.** In those rat precursor cultures, rapamycin blocked the shikimic-acid-associated rise in MBP, while the MEK inhibitor U0126 did not abolish it. PI3K inhibitors wortmannin and LY294002 reduced the elevated mTOR-phosphorylation readout toward control. These are joint experimental contrasts supporting pathway dependence; they do not establish that shikimic acid binds mTOR or that all MEK activity is irrelevant. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)
Complete structured claim and evidence
The PI3K inhibitor ly294002 reduced the SA-associated mTOR phosphorylation increase.
LY294002 → Rat OPC mTOR phosphorylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_condition
SA without the inhibitor present · LY294002 Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
SA without the inhibitor present · Shikimic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "ly294002 plus SA", "comparator": "SA without the inhibitor", "endpoint": "The PI3K inhibitor ly294002 reduced the SA-associated mTOR phosphorylation increase.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "ly294002", "state": "present"}, {"entity_slug": "shikimic-acid", "state": "present"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Primary rat OPC joint pharmacological perturbation.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
The PI3K inhibitor ly294002 reduced the SA-associated mTOR phosphorylation increase.
primary_references
Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/
source_locator
Reviewed reference lines 71-71; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 71–71
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Primary rat OPC joint pharmacological perturbation. · Recorded from source · Recorded from source
**Perturbations expose a conditional signaling route.** In those rat precursor cultures, rapamycin blocked the shikimic-acid-associated rise in MBP, while the MEK inhibitor U0126 did not abolish it. PI3K inhibitors wortmannin and LY294002 reduced the elevated mTOR-phosphorylation readout toward control. These are joint experimental contrasts supporting pathway dependence; they do not establish that shikimic acid binds mTOR or that all MEK activity is irrelevant. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)
Complete structured claim and evidence
The SA-treated LPC groups showed no significant reduction at day 7.
Shikimic acid → Mouse LPC-model demyelination volume Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA after LPC challenge", "comparator": "Vehicle after LPC challenge", "endpoint": "The SA-treated LPC groups showed no significant reduction at day 7.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse focal LPC demyelination; 100–200 mg/kg SA groups; day-specific histology.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Repair-time distinction, not proof of protection from initial injury or human MS efficacy.
plain_language
The SA-treated LPC groups showed no significant reduction at day 7.
primary_references
Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/
source_locator
Reviewed reference lines 73-73; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 73–73
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse focal LPC demyelination; 100–200 mg/kg SA groups; day-specific histology. · Recorded from source · Recorded from source
**Repair and injury prevention separated in time.** In the mouse focal lysolecithin model, shikimic acid groups did not have a smaller demyelinated region at day 7, but 100–200 mg/kg groups had less demyelination and more mature-oligodendrocyte staining at day 14. The article also reported improvement in EAE scores at 100–200 mg/kg, with a 50-mg/kg behavioral null. These model/time-dependent observations do not establish treatment of human multiple sclerosis. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)
Complete structured claim and evidence
The SA-treated LPC groups showed less demyelination at day 14.
Shikimic acid → Mouse LPC-model demyelination volume Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA after LPC challenge", "comparator": "Vehicle after LPC challenge", "endpoint": "The SA-treated LPC groups showed less demyelination at day 14.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse focal LPC demyelination; 100–200 mg/kg SA groups; day-specific histology.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Repair-time distinction, not proof of protection from initial injury or human MS efficacy.
plain_language
The SA-treated LPC groups showed less demyelination at day 14.
primary_references
Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/
source_locator
Reviewed reference lines 73-73; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 73–73
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse focal LPC demyelination; 100–200 mg/kg SA groups; day-specific histology. · Recorded from source · Recorded from source
**Repair and injury prevention separated in time.** In the mouse focal lysolecithin model, shikimic acid groups did not have a smaller demyelinated region at day 7, but 100–200 mg/kg groups had less demyelination and more mature-oligodendrocyte staining at day 14. The article also reported improvement in EAE scores at 100–200 mg/kg, with a 50-mg/kg behavioral null. These model/time-dependent observations do not establish treatment of human multiple sclerosis. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)
Complete structured claim and evidence
SA at 50 mg/kg showed no significant improvement in the EAE behavioral comparison.
Shikimic acid → Mouse EAE behavioral score Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA 50 mg/kg", "comparator": "EAE vehicle", "endpoint": "SA at 50 mg/kg showed no significant improvement in the EAE behavioral comparison.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse EAE model, dose-specific observation.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
SA at 50 mg/kg showed no significant improvement in the EAE behavioral comparison.
primary_references
Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/
source_locator
Reviewed reference lines 73-73; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 73–73
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse EAE model, dose-specific observation. · Recorded from source · Recorded from source
**Repair and injury prevention separated in time.** In the mouse focal lysolecithin model, shikimic acid groups did not have a smaller demyelinated region at day 7, but 100–200 mg/kg groups had less demyelination and more mature-oligodendrocyte staining at day 14. The article also reported improvement in EAE scores at 100–200 mg/kg, with a 50-mg/kg behavioral null. These model/time-dependent observations do not establish treatment of human multiple sclerosis. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)
Complete structured claim and evidence
SA at 100–200 mg/kg showed lower scores in the EAE behavioral comparison.
Shikimic acid → Mouse EAE behavioral score Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA 100–200 mg/kg", "comparator": "EAE vehicle", "endpoint": "SA at 100–200 mg/kg showed lower scores in the EAE behavioral comparison.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse EAE model, dose-specific observation.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
SA at 100–200 mg/kg showed lower scores in the EAE behavioral comparison.
primary_references
Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/
source_locator
Reviewed reference lines 73-73; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 73–73
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse EAE model, dose-specific observation. · Recorded from source · Recorded from source
**Repair and injury prevention separated in time.** In the mouse focal lysolecithin model, shikimic acid groups did not have a smaller demyelinated region at day 7, but 100–200 mg/kg groups had less demyelination and more mature-oligodendrocyte staining at day 14. The article also reported improvement in EAE scores at 100–200 mg/kg, with a 50-mg/kg behavioral null. These model/time-dependent observations do not establish treatment of human multiple sclerosis. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)
Complete structured claim and evidence
SA increased shaft elongation in isolated human follicles.
Shikimic acid → Human isolated hair-follicle shaft elongation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA", "comparator": "Vehicle", "endpoint": "SA increased shaft elongation in isolated human follicles.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Ex-vivo human follicles; 1/10 µM SA, 12-day culture.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Isolated tissue, not clinical oral or topical human hair regrowth.
plain_language
SA increased shaft elongation in isolated human follicles.
primary_references
Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle. | 2019 | DOI 10.1038/s41598-019-53612-5 | PMID 31740717 | https://pubmed.ncbi.nlm.nih.gov/31740717/ | https://doi.org/10.1038/s41598-019-53612-5 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6861222/
source_locator
Reviewed reference lines 75-75; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 75–75
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Ex-vivo human follicles; 1/10 µM SA, 12-day culture. · Recorded from source · Recorded from source
**Hair-follicle findings include human tissue, not a human treatment trial.** In isolated human hair follicles, 1 or 10 µM shikimic acid increased shaft elongation during 12-day culture. Dermal papilla cells showed higher MTT readouts, and 1 µM exposure increased MYC, HGF, KGF and VEGF transcripts at 24 h and p38/CREB phosphorylation at 15 min. Transcript increases are not proof of increased secreted growth-factor flux. Mannose-receptor staining establishes receptor presence, not that this receptor was necessary for the response. Topical 10–100 mM exposure also affected anagen-related measurements in mice; neither system establishes oral human hair regrowth. [Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle.](https://pubmed.ncbi.nlm.nih.gov/31740717/)
Complete structured claim and evidence
SA increased the HGF transcript readout in human dermal papilla cells.
Shikimic acid → Human hepatocyte growth factor / HGF Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA", "comparator": "Vehicle", "endpoint": "SA increased the HGF transcript readout in human dermal papilla cells.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human dermal papilla cells; 1 µM SA for 24 h, qPCR.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Transcript level is not measured secretion, target binding or clinical hair growth.
plain_language
SA increased the HGF transcript readout in human dermal papilla cells.
primary_references
Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle. | 2019 | DOI 10.1038/s41598-019-53612-5 | PMID 31740717 | https://pubmed.ncbi.nlm.nih.gov/31740717/ | https://doi.org/10.1038/s41598-019-53612-5 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6861222/
source_locator
Reviewed reference lines 75-75; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 75–75
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human dermal papilla cells; 1 µM SA for 24 h, qPCR. · Recorded from source · Recorded from source
**Hair-follicle findings include human tissue, not a human treatment trial.** In isolated human hair follicles, 1 or 10 µM shikimic acid increased shaft elongation during 12-day culture. Dermal papilla cells showed higher MTT readouts, and 1 µM exposure increased MYC, HGF, KGF and VEGF transcripts at 24 h and p38/CREB phosphorylation at 15 min. Transcript increases are not proof of increased secreted growth-factor flux. Mannose-receptor staining establishes receptor presence, not that this receptor was necessary for the response. Topical 10–100 mM exposure also affected anagen-related measurements in mice; neither system establishes oral human hair regrowth. [Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle.](https://pubmed.ncbi.nlm.nih.gov/31740717/)
Complete structured claim and evidence
SA increased the KGF/FGF7 transcript readout in human dermal papilla cells.
Shikimic acid → Human keratinocyte growth factor / FGF7 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA", "comparator": "Vehicle", "endpoint": "SA increased the KGF/FGF7 transcript readout in human dermal papilla cells.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human dermal papilla cells; 1 µM SA for 24 h, qPCR.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Transcript level is not measured secretion, target binding or clinical hair growth.
plain_language
SA increased the KGF/FGF7 transcript readout in human dermal papilla cells.
primary_references
Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle. | 2019 | DOI 10.1038/s41598-019-53612-5 | PMID 31740717 | https://pubmed.ncbi.nlm.nih.gov/31740717/ | https://doi.org/10.1038/s41598-019-53612-5 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6861222/
source_locator
Reviewed reference lines 75-75; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 75–75
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human dermal papilla cells; 1 µM SA for 24 h, qPCR. · Recorded from source · Recorded from source
**Hair-follicle findings include human tissue, not a human treatment trial.** In isolated human hair follicles, 1 or 10 µM shikimic acid increased shaft elongation during 12-day culture. Dermal papilla cells showed higher MTT readouts, and 1 µM exposure increased MYC, HGF, KGF and VEGF transcripts at 24 h and p38/CREB phosphorylation at 15 min. Transcript increases are not proof of increased secreted growth-factor flux. Mannose-receptor staining establishes receptor presence, not that this receptor was necessary for the response. Topical 10–100 mM exposure also affected anagen-related measurements in mice; neither system establishes oral human hair regrowth. [Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle.](https://pubmed.ncbi.nlm.nih.gov/31740717/)
Complete structured claim and evidence
SA increased the VEGF transcript readout in human dermal papilla cells.
Shikimic acid → Vascular endothelial growth factor A Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA", "comparator": "Vehicle", "endpoint": "SA increased the VEGF transcript readout in human dermal papilla cells.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human dermal papilla cells; 1 µM SA for 24 h, qPCR.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Transcript level is not measured secretion, target binding or clinical hair growth.
plain_language
SA increased the VEGF transcript readout in human dermal papilla cells.
primary_references
Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle. | 2019 | DOI 10.1038/s41598-019-53612-5 | PMID 31740717 | https://pubmed.ncbi.nlm.nih.gov/31740717/ | https://doi.org/10.1038/s41598-019-53612-5 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6861222/
source_locator
Reviewed reference lines 75-75; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 75–75
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human dermal papilla cells; 1 µM SA for 24 h, qPCR. · Recorded from source · Recorded from source
**Hair-follicle findings include human tissue, not a human treatment trial.** In isolated human hair follicles, 1 or 10 µM shikimic acid increased shaft elongation during 12-day culture. Dermal papilla cells showed higher MTT readouts, and 1 µM exposure increased MYC, HGF, KGF and VEGF transcripts at 24 h and p38/CREB phosphorylation at 15 min. Transcript increases are not proof of increased secreted growth-factor flux. Mannose-receptor staining establishes receptor presence, not that this receptor was necessary for the response. Topical 10–100 mM exposure also affected anagen-related measurements in mice; neither system establishes oral human hair regrowth. [Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle.](https://pubmed.ncbi.nlm.nih.gov/31740717/)
Complete structured claim and evidence
SA increased CREB phosphorylation in human dermal papilla cells.
Shikimic acid → Human cAMP response element-binding protein 1 / CREB1 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA", "comparator": "Vehicle", "endpoint": "SA increased CREB phosphorylation in human dermal papilla cells.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human cells; 1 µM SA, 15 min.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Signaling readout, not demonstrated direct receptor or kinase binding.
plain_language
SA increased CREB phosphorylation in human dermal papilla cells.
primary_references
Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle. | 2019 | DOI 10.1038/s41598-019-53612-5 | PMID 31740717 | https://pubmed.ncbi.nlm.nih.gov/31740717/ | https://doi.org/10.1038/s41598-019-53612-5 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6861222/
source_locator
Reviewed reference lines 75-75; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 75–75
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human cells; 1 µM SA, 15 min. · Recorded from source · Recorded from source
**Hair-follicle findings include human tissue, not a human treatment trial.** In isolated human hair follicles, 1 or 10 µM shikimic acid increased shaft elongation during 12-day culture. Dermal papilla cells showed higher MTT readouts, and 1 µM exposure increased MYC, HGF, KGF and VEGF transcripts at 24 h and p38/CREB phosphorylation at 15 min. Transcript increases are not proof of increased secreted growth-factor flux. Mannose-receptor staining establishes receptor presence, not that this receptor was necessary for the response. Topical 10–100 mM exposure also affected anagen-related measurements in mice; neither system establishes oral human hair regrowth. [Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle.](https://pubmed.ncbi.nlm.nih.gov/31740717/)
Complete structured claim and evidence
SA increased p38 phosphorylation in human dermal papilla cells.
Shikimic acid → Human dermal papilla p38 phosphorylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA", "comparator": "Vehicle", "endpoint": "SA increased p38 phosphorylation in human dermal papilla cells.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human cells; 1 µM SA, 15 min.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
SA increased p38 phosphorylation in human dermal papilla cells.
primary_references
Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle. | 2019 | DOI 10.1038/s41598-019-53612-5 | PMID 31740717 | https://pubmed.ncbi.nlm.nih.gov/31740717/ | https://doi.org/10.1038/s41598-019-53612-5 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6861222/
source_locator
Reviewed reference lines 75-75; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 75–75
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human cells; 1 µM SA, 15 min. · Recorded from source · Recorded from source
**Hair-follicle findings include human tissue, not a human treatment trial.** In isolated human hair follicles, 1 or 10 µM shikimic acid increased shaft elongation during 12-day culture. Dermal papilla cells showed higher MTT readouts, and 1 µM exposure increased MYC, HGF, KGF and VEGF transcripts at 24 h and p38/CREB phosphorylation at 15 min. Transcript increases are not proof of increased secreted growth-factor flux. Mannose-receptor staining establishes receptor presence, not that this receptor was necessary for the response. Topical 10–100 mM exposure also affected anagen-related measurements in mice; neither system establishes oral human hair regrowth. [Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle.](https://pubmed.ncbi.nlm.nih.gov/31740717/)
Complete structured claim and evidence
Mannose-receptor staining was present in the hair-follicle system, but necessity for the SA response was not established.
The macrophage mannose receptor → Human isolated hair-follicle shaft elongation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Human follicle immunostaining; unsigned contextual association.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
No direct receptor-binding or receptor-necessity edge asserted.
plain_language
Mannose-receptor staining was present in the hair-follicle system, but necessity for the SA response was not established.
primary_references
Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle. | 2019 | DOI 10.1038/s41598-019-53612-5 | PMID 31740717 | https://pubmed.ncbi.nlm.nih.gov/31740717/ | https://doi.org/10.1038/s41598-019-53612-5 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6861222/
source_locator
Reviewed reference lines 75-75; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 75–75
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human follicle immunostaining; unsigned contextual association. · Recorded from source · Recorded from source
**Hair-follicle findings include human tissue, not a human treatment trial.** In isolated human hair follicles, 1 or 10 µM shikimic acid increased shaft elongation during 12-day culture. Dermal papilla cells showed higher MTT readouts, and 1 µM exposure increased MYC, HGF, KGF and VEGF transcripts at 24 h and p38/CREB phosphorylation at 15 min. Transcript increases are not proof of increased secreted growth-factor flux. Mannose-receptor staining establishes receptor presence, not that this receptor was necessary for the response. Topical 10–100 mM exposure also affected anagen-related measurements in mice; neither system establishes oral human hair regrowth. [Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle.](https://pubmed.ncbi.nlm.nih.gov/31740717/)
Complete structured claim and evidence
SA reduced lipid staining in the tested human hepatoma cell contexts.
Shikimic acid → Human hepatoma-cell lipid staining after shikimic acid Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA treatment", "comparator": "Matched untreated cells", "endpoint": "SA reduced lipid staining in the tested human hepatoma cell contexts.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
HepG2/Huh7 cell study; full source retained, exact individual dose unextracted.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Cell staining is not human fatty-liver treatment efficacy.
plain_language
SA reduced lipid staining in the tested human hepatoma cell contexts.
primary_references
Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC. | 2019 | DOI 10.3390/ijms20030582 | PMID 30700011 | https://pubmed.ncbi.nlm.nih.gov/30700011/ | https://doi.org/10.3390/ijms20030582 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6387373/
source_locator
Reviewed reference lines 77-77; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 77–77
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · HepG2/Huh7 cell study; full source retained, exact individual dose unextracted. · Recorded from source · Recorded from source
**Lipid accumulation studies identify responses, not direct inhibition.** In HepG2/Huh7 and 3T3-L1 experiments, shikimic acid was associated with lower lipid staining and altered lipogenic proteins, including lower MID1IP1, LXRα and SREBP-1c; AMPKα and ACC phosphorylation increased in the reported cell contexts. Genetic manipulation of MID1IP1 and compound-C experiments probed pathway involvement. These cultured-cell observations do not prove direct binding to MID1IP1, human fatty-liver efficacy, or that AMPK causes the triglyceride change in the separate mouse-feeding study. Individual cell-dose details remain in the original paper rather than being guessed. [Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC.](https://pubmed.ncbi.nlm.nih.gov/30700011/)
Complete structured claim and evidence
SA lowered MID1IP1 expression in the tested human hepatoma cells.
Shikimic acid → Human MID1 interacting protein 1 / MID1IP1 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA treatment", "comparator": "Matched untreated cells", "endpoint": "SA lowered MID1IP1 expression in the tested human hepatoma cells.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
HepG2/Huh7 24-hour expression assays.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Expression response, not direct binding or purified-enzyme inhibition.
plain_language
SA lowered MID1IP1 expression in the tested human hepatoma cells.
primary_references
Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC. | 2019 | DOI 10.3390/ijms20030582 | PMID 30700011 | https://pubmed.ncbi.nlm.nih.gov/30700011/ | https://doi.org/10.3390/ijms20030582 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6387373/
source_locator
Reviewed reference lines 77-77; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 77–77
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · HepG2/Huh7 24-hour expression assays. · Recorded from source · Recorded from source
**Lipid accumulation studies identify responses, not direct inhibition.** In HepG2/Huh7 and 3T3-L1 experiments, shikimic acid was associated with lower lipid staining and altered lipogenic proteins, including lower MID1IP1, LXRα and SREBP-1c; AMPKα and ACC phosphorylation increased in the reported cell contexts. Genetic manipulation of MID1IP1 and compound-C experiments probed pathway involvement. These cultured-cell observations do not prove direct binding to MID1IP1, human fatty-liver efficacy, or that AMPK causes the triglyceride change in the separate mouse-feeding study. Individual cell-dose details remain in the original paper rather than being guessed. [Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC.](https://pubmed.ncbi.nlm.nih.gov/30700011/)
Complete structured claim and evidence
SA increased Human HepG2 AMPK phosphorylation.
Shikimic acid → Human HepG2 AMPK phosphorylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA treatment", "comparator": "Matched untreated cells", "endpoint": "SA increased Human HepG2 AMPK phosphorylation.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human HepG2 cell signaling assay.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Context-specific signaling; no asserted mediation of a separate in-vivo lipid effect.
plain_language
SA increased Human HepG2 AMPK phosphorylation.
primary_references
Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC. | 2019 | DOI 10.3390/ijms20030582 | PMID 30700011 | https://pubmed.ncbi.nlm.nih.gov/30700011/ | https://doi.org/10.3390/ijms20030582 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6387373/
source_locator
Reviewed reference lines 77-77; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 77–77
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human HepG2 cell signaling assay. · Recorded from source · Recorded from source
**Lipid accumulation studies identify responses, not direct inhibition.** In HepG2/Huh7 and 3T3-L1 experiments, shikimic acid was associated with lower lipid staining and altered lipogenic proteins, including lower MID1IP1, LXRα and SREBP-1c; AMPKα and ACC phosphorylation increased in the reported cell contexts. Genetic manipulation of MID1IP1 and compound-C experiments probed pathway involvement. These cultured-cell observations do not prove direct binding to MID1IP1, human fatty-liver efficacy, or that AMPK causes the triglyceride change in the separate mouse-feeding study. Individual cell-dose details remain in the original paper rather than being guessed. [Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC.](https://pubmed.ncbi.nlm.nih.gov/30700011/)
Complete structured claim and evidence
SA increased Human HepG2 ACC phosphorylation.
Shikimic acid → Human HepG2 ACC phosphorylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "SA treatment", "comparator": "Matched untreated cells", "endpoint": "SA increased Human HepG2 ACC phosphorylation.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human HepG2 cell signaling assay.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Context-specific signaling; no asserted mediation of a separate in-vivo lipid effect.
plain_language
SA increased Human HepG2 ACC phosphorylation.
primary_references
Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC. | 2019 | DOI 10.3390/ijms20030582 | PMID 30700011 | https://pubmed.ncbi.nlm.nih.gov/30700011/ | https://doi.org/10.3390/ijms20030582 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6387373/
source_locator
Reviewed reference lines 77-77; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 77–77
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human HepG2 cell signaling assay. · Recorded from source · Recorded from source
**Lipid accumulation studies identify responses, not direct inhibition.** In HepG2/Huh7 and 3T3-L1 experiments, shikimic acid was associated with lower lipid staining and altered lipogenic proteins, including lower MID1IP1, LXRα and SREBP-1c; AMPKα and ACC phosphorylation increased in the reported cell contexts. Genetic manipulation of MID1IP1 and compound-C experiments probed pathway involvement. These cultured-cell observations do not prove direct binding to MID1IP1, human fatty-liver efficacy, or that AMPK causes the triglyceride change in the separate mouse-feeding study. Individual cell-dose details remain in the original paper rather than being guessed. [Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC.](https://pubmed.ncbi.nlm.nih.gov/30700011/)
Complete structured claim and evidence
Compound C did not alter MID1IP1 expression in the tested HepG2 comparison.
Compound C AMPK inhibitor → Human MID1 interacting protein 1 / MID1IP1 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "Compound C in the recorded comparison", "comparator": "Matched comparison without compound C", "endpoint": "Compound C did not alter MID1IP1 expression in the tested HepG2 comparison.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human HepG2 pharmacological signaling experiment.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Assay-specific null, not proof of perfect AMPK specificity or absence of all AMPK involvement.
plain_language
Compound C did not alter MID1IP1 expression in the tested HepG2 comparison.
primary_references
Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC. | 2019 | DOI 10.3390/ijms20030582 | PMID 30700011 | https://pubmed.ncbi.nlm.nih.gov/30700011/ | https://doi.org/10.3390/ijms20030582 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6387373/
source_locator
Reviewed reference lines 81-81; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 81–81
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human HepG2 pharmacological signaling experiment. · Recorded from source · Recorded from source
**The lipid study contains a useful null result.** Depleting MID1IP1 by siRNA in HepG2 cells reduced SREBP-1c and FAS expression and increased AMPK/ACC phosphorylation. In mouse AML-12 cells, MID1IP1 overexpression attenuated AMPK phosphorylation associated with 80 µM shikimic acid. Conversely, compound C did not alter MID1IP1 expression in the tested HepG2 comparison. This limits a simple claim that AMPK inhibition must reverse every MID1IP1 response. The source tested 10–160 µM SA in viability assays; MTT could fall to about 70% of control at the highest concentration, so reduced lipid staining must not be interpreted without viability context. [Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC.](https://pubmed.ncbi.nlm.nih.gov/30700011/)
Complete structured claim and evidence
MID1IP1 siRNA depletion increased AMPK phosphorylation in HepG2 cells.
Human MID1 interacting protein 1 / MID1IP1 → Human HepG2 AMPK phosphorylation Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_contrast
{"intervention": "MID1IP1 siRNA depletion", "comparator": "Control transfection", "endpoint": "MID1IP1 siRNA depletion increased AMPK phosphorylation in HepG2 cells.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human HepG2 genetic perturbation.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
The subject is depleted, not added; this is not an ordinary positive effect of MID1IP1 abundance.
plain_language
MID1IP1 siRNA depletion increased AMPK phosphorylation in HepG2 cells.
primary_references
Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC. | 2019 | DOI 10.3390/ijms20030582 | PMID 30700011 | https://pubmed.ncbi.nlm.nih.gov/30700011/ | https://doi.org/10.3390/ijms20030582 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6387373/
source_locator
Reviewed reference lines 81-81; exact primary location described in quoted passage where extracted.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 81–81
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human HepG2 genetic perturbation. · Recorded from source · Recorded from source
**The lipid study contains a useful null result.** Depleting MID1IP1 by siRNA in HepG2 cells reduced SREBP-1c and FAS expression and increased AMPK/ACC phosphorylation. In mouse AML-12 cells, MID1IP1 overexpression attenuated AMPK phosphorylation associated with 80 µM shikimic acid. Conversely, compound C did not alter MID1IP1 expression in the tested HepG2 comparison. This limits a simple claim that AMPK inhibition must reverse every MID1IP1 response. The source tested 10–160 µM SA in viability assays; MTT could fall to about 70% of control at the highest concentration, so reduced lipid staining must not be interpreted without viability context. [Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC.](https://pubmed.ncbi.nlm.nih.gov/30700011/)
Complete structured claim and evidence
The 0.03 wt% mixture lowered the type-I 5α-reductase ELISA signal more than SA alone under testosterone challenge.
Shikimic acid and Prunus mume extract 1:1 mixture → Human sebocyte type-I 5-alpha-reductase ELISA amount Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text methods/results reviewed. Published January 2026 despite 2025 in DOI.
experimental_contrast
{"intervention": "1:1 SA/P. mume mixture plus testosterone", "comparator": "SA alone plus testosterone", "endpoint": "The 0.03 wt% mixture lowered the type-I 5α-reductase ELISA signal more than SA alone under testosterone challenge.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human sebocytes; 10 nM testosterone, 72 h; three technical replicates.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
ELISA protein amount in processed supernatant, not catalytic inhibition. No total-protein normalization or independent biological replication established.
plain_language
The 0.03 wt% mixture lowered the type-I 5α-reductase ELISA signal more than SA alone under testosterone challenge.
primary_references
Novel prospectives of shikimic acid and Prunus mume extract for enhancing bioactivity on 5α-reductase and stability in cosmetic patches for acne treatment | 2026 | DOI 10.3389/fntpr.2025.1737986 | https://www.frontiersin.org/journals/natural-products/articles/10.3389/fntpr.2025.1737986/full
source_locator
Reviewed reference lines 79-79; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 79–79
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human sebocytes; 10 nM testosterone, 72 h; three technical replicates. · Recorded from source · Recorded from source
**A 2026 topical study measured protein amount.** Human sebocytes challenged with 10 nM testosterone were exposed for 72 h to shikimic acid or a 1:1 shikimic-acid/Prunus mume extract mixture. At 0.03 wt%, the mixture lowered the reported type-I 5α-reductase ELISA signal more than shikimic acid alone. The assay measured protein amount in processed supernatant, with three technical replicates and no total-protein normalization; it was not a testosterone-to-DHT catalytic assay. Docking is not measured affinity. Thus a direct 5α-reductase inhibition claim is not justified by this experiment. [Novel prospectives of shikimic acid and Prunus mume extract for enhancing bioactivity on 5α-reductase and stability in cosmetic patches for acne treatment](https://www.frontiersin.org/journals/natural-products/articles/10.3389/fntpr.2025.1737986/full)
Complete structured claim and evidence
Skin sebum decreased over 48 hours with the shikimic-acid-prunus-patch-2026 intervention.
2026 mixed shikimic-acid/Prunus-mume acne patch → Human skin sebum during the 2026 patch study Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text methods/results reviewed. Published January 2026 despite 2025 in DOI.
experimental_contrast
{"intervention": "Specified patch", "comparator": "Same treated site before patch", "endpoint": "Skin sebum decreased over 48 hours with the shikimic-acid-prunus-patch-2026 intervention.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
15 volunteers, open-label nonrandomized split-body comparison.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Mixed formulation or active comparator; no placebo isolation or isolated SA clinical efficacy.
plain_language
Skin sebum decreased over 48 hours with the shikimic-acid-prunus-patch-2026 intervention.
primary_references
Novel prospectives of shikimic acid and Prunus mume extract for enhancing bioactivity on 5α-reductase and stability in cosmetic patches for acne treatment | 2026 | DOI 10.3389/fntpr.2025.1737986 | https://www.frontiersin.org/journals/natural-products/articles/10.3389/fntpr.2025.1737986/full
source_locator
Reviewed reference lines 83-83; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 83–83
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · 15 volunteers, open-label nonrandomized split-body comparison. · Recorded from source · Recorded from source
**A mixed patch does not isolate shikimic acid efficacy.** The same report studied patches containing 0.5% shikimic acid and 0.5% P. mume extract plus additional formulation constituents in 15 volunteers aged 18–28. It was open-label, nonrandomized and split-body, over 48 h. Sebum decreased with both this patch and a 0.5% salicylic-acid comparator; the between-patch difference was not significant (p=0.12). No adverse skin effects were reported in this small short study. It does not establish isolated shikimic acid efficacy, long-term safety, oral antiandrogen action or synergy. [Novel prospectives of shikimic acid and Prunus mume extract for enhancing bioactivity on 5α-reductase and stability in cosmetic patches for acne treatment](https://www.frontiersin.org/journals/natural-products/articles/10.3389/fntpr.2025.1737986/full)
Complete structured claim and evidence
Skin sebum decreased over 48 hours with the salicylic-acid-patch-2026 intervention.
2026 comparator salicylic-acid acne patch → Human skin sebum during the 2026 patch study Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text methods/results reviewed. Published January 2026 despite 2025 in DOI.
experimental_contrast
{"intervention": "Specified patch", "comparator": "Same treated site before patch", "endpoint": "Skin sebum decreased over 48 hours with the salicylic-acid-patch-2026 intervention.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
15 volunteers, open-label nonrandomized split-body comparison.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Mixed formulation or active comparator; no placebo isolation or isolated SA clinical efficacy.
plain_language
Skin sebum decreased over 48 hours with the salicylic-acid-patch-2026 intervention.
primary_references
Novel prospectives of shikimic acid and Prunus mume extract for enhancing bioactivity on 5α-reductase and stability in cosmetic patches for acne treatment | 2026 | DOI 10.3389/fntpr.2025.1737986 | https://www.frontiersin.org/journals/natural-products/articles/10.3389/fntpr.2025.1737986/full
source_locator
Reviewed reference lines 83-83; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 83–83
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · 15 volunteers, open-label nonrandomized split-body comparison. · Recorded from source · Recorded from source
**A mixed patch does not isolate shikimic acid efficacy.** The same report studied patches containing 0.5% shikimic acid and 0.5% P. mume extract plus additional formulation constituents in 15 volunteers aged 18–28. It was open-label, nonrandomized and split-body, over 48 h. Sebum decreased with both this patch and a 0.5% salicylic-acid comparator; the between-patch difference was not significant (p=0.12). No adverse skin effects were reported in this small short study. It does not establish isolated shikimic acid efficacy, long-term safety, oral antiandrogen action or synergy. [Novel prospectives of shikimic acid and Prunus mume extract for enhancing bioactivity on 5α-reductase and stability in cosmetic patches for acne treatment](https://www.frontiersin.org/journals/natural-products/articles/10.3389/fntpr.2025.1737986/full)
Complete structured claim and evidence
The between-patch sebum difference did not reach significance (p=0.12).
2026 mixed shikimic-acid/Prunus-mume acne patch → Human skin sebum during the 2026 patch study Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text methods/results reviewed. Published January 2026 despite 2025 in DOI.
experimental_contrast
{"intervention": "Mixed SA/P. mume patch", "comparator": "0.5% salicylic-acid patch", "endpoint": "The between-patch sebum difference did not reach significance (p=0.12).", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Same 15-person 48-hour study.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Nonsignificance does not establish equivalence or synergy.
plain_language
The between-patch sebum difference did not reach significance (p=0.12).
primary_references
Novel prospectives of shikimic acid and Prunus mume extract for enhancing bioactivity on 5α-reductase and stability in cosmetic patches for acne treatment | 2026 | DOI 10.3389/fntpr.2025.1737986 | https://www.frontiersin.org/journals/natural-products/articles/10.3389/fntpr.2025.1737986/full
source_locator
Reviewed reference lines 83-83; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 83–83
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Same 15-person 48-hour study. · Recorded from source · Recorded from source
**A mixed patch does not isolate shikimic acid efficacy.** The same report studied patches containing 0.5% shikimic acid and 0.5% P. mume extract plus additional formulation constituents in 15 volunteers aged 18–28. It was open-label, nonrandomized and split-body, over 48 h. Sebum decreased with both this patch and a 0.5% salicylic-acid comparator; the between-patch difference was not significant (p=0.12). No adverse skin effects were reported in this small short study. It does not establish isolated shikimic acid efficacy, long-term safety, oral antiandrogen action or synergy. [Novel prospectives of shikimic acid and Prunus mume extract for enhancing bioactivity on 5α-reductase and stability in cosmetic patches for acne treatment](https://www.frontiersin.org/journals/natural-products/articles/10.3389/fntpr.2025.1737986/full)
Complete structured claim and evidence
The rat tracer study recovered shikimate-derived carbon in hippuric-acid.
Shikimic acid → Hippuric acid / benzoylglycine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Rat oral tracer study; gut-dependent metabolism with host processing.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Multistep tracer fate, not one direct host enzyme reaction or identical quantitative human metabolism.
plain_language
The rat tracer study recovered shikimate-derived carbon in hippuric-acid.
primary_references
The metabolism of shikimate in the rat. | 1978 | DOI 10.1042/bj1700257 | PMID 637841 | https://pubmed.ncbi.nlm.nih.gov/637841/ | https://doi.org/10.1042/bj1700257 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1183892/
source_locator
Reviewed reference lines 85-85; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 85–85
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Rat oral tracer study; gut-dependent metabolism with host processing. · Recorded from source · Recorded from source
**Gut metabolism and host conjugation must be distinguished.** The 1978 rat study traced oral shikimic acid into urinary hippurate, hexahydrohippurate, tetrahydrohippurate, two dihydroxycyclohexanecarboxylate isomers, catechol conjugates and expired CO2. Antibiotic treatment suppressed the characteristic conversion, implicating initial gut-microbial transformations. Host metabolism of microbial products still occurs. Hippurate contains a glycine conjugate, but product detection does not establish clinically significant glycine depletion or an identical human quantitative pathway. No assertion that parent shikimic acid is directly converted to every final product in one reaction is made. [The metabolism of shikimate in the rat.](https://pubmed.ncbi.nlm.nih.gov/637841/)
Complete structured claim and evidence
The rat tracer study recovered shikimate-derived carbon in hexahydrohippuric-acid.
Shikimic acid → Hexahydrohippuric acid Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Rat oral tracer study; gut-dependent metabolism with host processing.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Multistep tracer fate, not one direct host enzyme reaction or identical quantitative human metabolism.
plain_language
The rat tracer study recovered shikimate-derived carbon in hexahydrohippuric-acid.
primary_references
The metabolism of shikimate in the rat. | 1978 | DOI 10.1042/bj1700257 | PMID 637841 | https://pubmed.ncbi.nlm.nih.gov/637841/ | https://doi.org/10.1042/bj1700257 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1183892/
source_locator
Reviewed reference lines 85-85; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 85–85
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Rat oral tracer study; gut-dependent metabolism with host processing. · Recorded from source · Recorded from source
**Gut metabolism and host conjugation must be distinguished.** The 1978 rat study traced oral shikimic acid into urinary hippurate, hexahydrohippurate, tetrahydrohippurate, two dihydroxycyclohexanecarboxylate isomers, catechol conjugates and expired CO2. Antibiotic treatment suppressed the characteristic conversion, implicating initial gut-microbial transformations. Host metabolism of microbial products still occurs. Hippurate contains a glycine conjugate, but product detection does not establish clinically significant glycine depletion or an identical human quantitative pathway. No assertion that parent shikimic acid is directly converted to every final product in one reaction is made. [The metabolism of shikimate in the rat.](https://pubmed.ncbi.nlm.nih.gov/637841/)
Complete structured claim and evidence
The rat tracer study recovered shikimate-derived carbon in tetrahydrohippuric-acid.
Shikimic acid → 3,4,5,6-Tetrahydrohippuric acid Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Rat oral tracer study; gut-dependent metabolism with host processing.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Multistep tracer fate, not one direct host enzyme reaction or identical quantitative human metabolism.
plain_language
The rat tracer study recovered shikimate-derived carbon in tetrahydrohippuric-acid.
primary_references
The metabolism of shikimate in the rat. | 1978 | DOI 10.1042/bj1700257 | PMID 637841 | https://pubmed.ncbi.nlm.nih.gov/637841/ | https://doi.org/10.1042/bj1700257 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1183892/
source_locator
Reviewed reference lines 85-85; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 85–85
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Rat oral tracer study; gut-dependent metabolism with host processing. · Recorded from source · Recorded from source
**Gut metabolism and host conjugation must be distinguished.** The 1978 rat study traced oral shikimic acid into urinary hippurate, hexahydrohippurate, tetrahydrohippurate, two dihydroxycyclohexanecarboxylate isomers, catechol conjugates and expired CO2. Antibiotic treatment suppressed the characteristic conversion, implicating initial gut-microbial transformations. Host metabolism of microbial products still occurs. Hippurate contains a glycine conjugate, but product detection does not establish clinically significant glycine depletion or an identical human quantitative pathway. No assertion that parent shikimic acid is directly converted to every final product in one reaction is made. [The metabolism of shikimate in the rat.](https://pubmed.ncbi.nlm.nih.gov/637841/)
Complete structured claim and evidence
The rat tracer study recovered shikimate-derived carbon in shikimate-derived-dihydroxycyclohexanecarboxylates.
Shikimic acid → Shikimate-derived dihydroxycyclohexanecarboxylate isomers Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Rat oral tracer study; gut-dependent metabolism with host processing.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Multistep tracer fate, not one direct host enzyme reaction or identical quantitative human metabolism.
plain_language
The rat tracer study recovered shikimate-derived carbon in shikimate-derived-dihydroxycyclohexanecarboxylates.
primary_references
The metabolism of shikimate in the rat. | 1978 | DOI 10.1042/bj1700257 | PMID 637841 | https://pubmed.ncbi.nlm.nih.gov/637841/ | https://doi.org/10.1042/bj1700257 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1183892/
source_locator
Reviewed reference lines 85-85; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 85–85
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Rat oral tracer study; gut-dependent metabolism with host processing. · Recorded from source · Recorded from source
**Gut metabolism and host conjugation must be distinguished.** The 1978 rat study traced oral shikimic acid into urinary hippurate, hexahydrohippurate, tetrahydrohippurate, two dihydroxycyclohexanecarboxylate isomers, catechol conjugates and expired CO2. Antibiotic treatment suppressed the characteristic conversion, implicating initial gut-microbial transformations. Host metabolism of microbial products still occurs. Hippurate contains a glycine conjugate, but product detection does not establish clinically significant glycine depletion or an identical human quantitative pathway. No assertion that parent shikimic acid is directly converted to every final product in one reaction is made. [The metabolism of shikimate in the rat.](https://pubmed.ncbi.nlm.nih.gov/637841/)
Complete structured claim and evidence
The rat tracer study recovered shikimate-derived carbon in catechol-conjugates.
Shikimic acid → Catechol conjugates, unresolved individual forms Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Rat oral tracer study; gut-dependent metabolism with host processing.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Multistep tracer fate, not one direct host enzyme reaction or identical quantitative human metabolism.
plain_language
The rat tracer study recovered shikimate-derived carbon in catechol-conjugates.
primary_references
The metabolism of shikimate in the rat. | 1978 | DOI 10.1042/bj1700257 | PMID 637841 | https://pubmed.ncbi.nlm.nih.gov/637841/ | https://doi.org/10.1042/bj1700257 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1183892/
source_locator
Reviewed reference lines 85-85; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 85–85
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Rat oral tracer study; gut-dependent metabolism with host processing. · Recorded from source · Recorded from source
**Gut metabolism and host conjugation must be distinguished.** The 1978 rat study traced oral shikimic acid into urinary hippurate, hexahydrohippurate, tetrahydrohippurate, two dihydroxycyclohexanecarboxylate isomers, catechol conjugates and expired CO2. Antibiotic treatment suppressed the characteristic conversion, implicating initial gut-microbial transformations. Host metabolism of microbial products still occurs. Hippurate contains a glycine conjugate, but product detection does not establish clinically significant glycine depletion or an identical human quantitative pathway. No assertion that parent shikimic acid is directly converted to every final product in one reaction is made. [The metabolism of shikimate in the rat.](https://pubmed.ncbi.nlm.nih.gov/637841/)
Complete structured claim and evidence
Antibiotic treatment suppressed characteristic shikimate-derived metabolic products in rats.
Shikimic acid → Rat gut-dependent shikimate biotransformation Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_contrast
{"intervention": "Shikimic acid after antibiotic treatment", "comparator": "Shikimic acid without antibiotic treatment", "endpoint": "Antibiotic treatment suppressed characteristic shikimate-derived metabolic products in rats.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Rat oral tracer study with antibiotic perturbation.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Broad microbial perturbation, not selective EPSPS inhibition or lack of host metabolism.
plain_language
Antibiotic treatment suppressed characteristic shikimate-derived metabolic products in rats.
primary_references
The metabolism of shikimate in the rat. | 1978 | DOI 10.1042/bj1700257 | PMID 637841 | https://pubmed.ncbi.nlm.nih.gov/637841/ | https://doi.org/10.1042/bj1700257 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1183892/
source_locator
Reviewed reference lines 85-85; exact primary location described in quoted passage where extracted.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 85–85
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Rat oral tracer study with antibiotic perturbation. · Recorded from source · Recorded from source
**Gut metabolism and host conjugation must be distinguished.** The 1978 rat study traced oral shikimic acid into urinary hippurate, hexahydrohippurate, tetrahydrohippurate, two dihydroxycyclohexanecarboxylate isomers, catechol conjugates and expired CO2. Antibiotic treatment suppressed the characteristic conversion, implicating initial gut-microbial transformations. Host metabolism of microbial products still occurs. Hippurate contains a glycine conjugate, but product detection does not establish clinically significant glycine depletion or an identical human quantitative pathway. No assertion that parent shikimic acid is directly converted to every final product in one reaction is made. [The metabolism of shikimate in the rat.](https://pubmed.ncbi.nlm.nih.gov/637841/)
Complete structured claim and evidence
The studied E. coli AroE system supported NADP+-dependent DHS oxidation toward gallic acid.
3-Dehydroshikimate / DHS → Gallic acid Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Purified enzyme oxidative branch with subsequent spontaneous aromatization proposed in the paper, distinct from NADPH-driven DHS reduction.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
The studied E. coli AroE system supported NADP+-dependent DHS oxidation toward gallic acid.
primary_references
Mechanism of gallic acid biosynthesis in bacteria (Escherichia coli) and walnut (Juglans regia). | 2011 | DOI 10.1007/s11103-011-9739-3 | PMID 21279669 | https://pubmed.ncbi.nlm.nih.gov/21279669/ | https://doi.org/10.1007/s11103-011-9739-3 | https://pmc.ncbi.nlm.nih.gov/articles/PMC3057006/
source_locator
Reviewed reference lines 87-87; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 87–87
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Purified enzyme oxidative branch with subsequent spontaneous aromatization proposed in the paper, distinct from NADPH-driven DHS reduction. · Recorded from source · Recorded from source
**A plant oxidative branch is not a human metabolic pathway.** Walnut shikimate-dehydrogenase work and E. coli AroE assays support oxidation of DHS toward gallic acid with NADP+ in the studied enzyme systems; expression of walnut JrSDH in tobacco increased gallic-acid accumulation. This branch shows why substrate and redox context matter for enzyme function. It is not evidence that oral shikimic acid is converted into gallic acid by a human shikimate pathway. [Mechanism of gallic acid biosynthesis in bacteria (Escherichia coli) and walnut (Juglans regia).](https://pubmed.ncbi.nlm.nih.gov/21279669/)
Complete structured claim and evidence
Walnut shikimate dehydrogenase supports the studied oxidative route toward gallic acid.
3-Dehydroshikimate / DHS → Gallic acid Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.
experimental_model
Walnut enzyme assays and transgenic tobacco context; not a human pathway.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
plain_language
Walnut shikimate dehydrogenase supports the studied oxidative route toward gallic acid.
primary_references
Mechanism of gallic acid biosynthesis in bacteria (Escherichia coli) and walnut (Juglans regia). | 2011 | DOI 10.1007/s11103-011-9739-3 | PMID 21279669 | https://pubmed.ncbi.nlm.nih.gov/21279669/ | https://doi.org/10.1007/s11103-011-9739-3 | https://pmc.ncbi.nlm.nih.gov/articles/PMC3057006/
source_locator
Reviewed reference lines 87-87; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 87–87
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Walnut enzyme assays and transgenic tobacco context; not a human pathway. · Recorded from source · Recorded from source
**A plant oxidative branch is not a human metabolic pathway.** Walnut shikimate-dehydrogenase work and E. coli AroE assays support oxidation of DHS toward gallic acid with NADP+ in the studied enzyme systems; expression of walnut JrSDH in tobacco increased gallic-acid accumulation. This branch shows why substrate and redox context matter for enzyme function. It is not evidence that oral shikimic acid is converted into gallic acid by a human shikimate pathway. [Mechanism of gallic acid biosynthesis in bacteria (Escherichia coli) and walnut (Juglans regia).](https://pubmed.ncbi.nlm.nih.gov/21279669/)
Complete structured claim and evidence
Anisatin inhibited GABA-activated current in a use-dependent manner, estimated EC50 1.10 µM.
Anisatin → Rat DRG GABA-activated current in anisatin assays Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_contrast
{"intervention": "Anisatin during GABA activation", "comparator": "GABA activation without anisatin", "endpoint": "Anisatin inhibited GABA-activated current in a use-dependent manner, estimated EC50 1.10 µM.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Rat dorsal-root-ganglion electrophysiology.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Different molecule from shikimic acid; not proof of parent-compound toxicity.
plain_language
Anisatin inhibited GABA-activated current in a use-dependent manner, estimated EC50 1.10 µM.
primary_references
Anisatin modulation of the gamma-aminobutyric acid receptor-channel in rat dorsal root ganglion neurons. | 1999 | DOI 10.1038/sj.bjp.0702700 | PMID 10455311 | https://pubmed.ncbi.nlm.nih.gov/10455311/ | https://doi.org/10.1038/sj.bjp.0702700 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1566146/
primary_references
Neurotoxicities in infants seen with the consumption of star anise tea. | 2004 | DOI 10.1542/peds.2004-0058 | PMID 15492355 | https://pubmed.ncbi.nlm.nih.gov/15492355/ | https://doi.org/10.1542/peds.2004-0058
source_locator
Reviewed reference lines 89-89; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 89–89
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Rat dorsal-root-ganglion electrophysiology. · Recorded from source · Recorded from source
**Star-anise toxicity is a preparation-identity issue.** Anisatin inhibited GABA-activated currents in rat dorsal-root-ganglion neurons in a use-dependent fashion; an estimated EC50 was 1.10 µM. It is a different molecule from shikimic acid. Seven infant neurological cases associated with star-anise tea and evidence of toxic species contamination demonstrate preparation risk, not toxicity attributable specifically to purified shikimic acid. Botanical identity, plant part, contamination, extraction and measured composition cannot be inferred from the name star anise. [Anisatin modulation of the gamma-aminobutyric acid receptor-channel in rat dorsal root ganglion neurons.](https://pubmed.ncbi.nlm.nih.gov/10455311/) [Neurotoxicities in infants seen with the consumption of star anise tea.](https://pubmed.ncbi.nlm.nih.gov/15492355/)
Complete structured claim and evidence
Seven infant neurological cases were associated with star-anise tea in the report.
Star-anise tea of uncertain botanical purity → Infant neurological cases associated with star-anise tea Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Human case series with evidence of botanical contamination.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Preparation-level association, not isolated shikimic-acid causality.
plain_language
Seven infant neurological cases were associated with star-anise tea in the report.
primary_references
Anisatin modulation of the gamma-aminobutyric acid receptor-channel in rat dorsal root ganglion neurons. | 1999 | DOI 10.1038/sj.bjp.0702700 | PMID 10455311 | https://pubmed.ncbi.nlm.nih.gov/10455311/ | https://doi.org/10.1038/sj.bjp.0702700 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1566146/
primary_references
Neurotoxicities in infants seen with the consumption of star anise tea. | 2004 | DOI 10.1542/peds.2004-0058 | PMID 15492355 | https://pubmed.ncbi.nlm.nih.gov/15492355/ | https://doi.org/10.1542/peds.2004-0058
source_locator
Reviewed reference lines 89-89; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 89–89
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human case series with evidence of botanical contamination. · Recorded from source · Recorded from source
**Star-anise toxicity is a preparation-identity issue.** Anisatin inhibited GABA-activated currents in rat dorsal-root-ganglion neurons in a use-dependent fashion; an estimated EC50 was 1.10 µM. It is a different molecule from shikimic acid. Seven infant neurological cases associated with star-anise tea and evidence of toxic species contamination demonstrate preparation risk, not toxicity attributable specifically to purified shikimic acid. Botanical identity, plant part, contamination, extraction and measured composition cannot be inferred from the name star anise. [Anisatin modulation of the gamma-aminobutyric acid receptor-channel in rat dorsal root ganglion neurons.](https://pubmed.ncbi.nlm.nih.gov/10455311/) [Neurotoxicities in infants seen with the consumption of star anise tea.](https://pubmed.ncbi.nlm.nih.gov/15492355/)
Complete structured claim and evidence
The triacetylshikimic-acid record is a distinct-compound or preparation comparison; its biological effects are not assigned to isolated shikimic acid.
Shikimic acid → Triacetylshikimic acid / TSA Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Editorial identity/scope connection, not experimental causation.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Unsigned navigation, not a human metabolic conversion or automatic ingredient attribution.
plain_language
The triacetylshikimic-acid record is a distinct-compound or preparation comparison; its biological effects are not assigned to isolated shikimic acid.
primary_references
Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid. | 2016 | DOI 10.3109/13880209.2016.1153663 | PMID 27609150 | https://pubmed.ncbi.nlm.nih.gov/27609150/ | https://doi.org/10.3109/13880209.2016.1153663
primary_references
Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats. | 2002 | DOI 10.1097/00005344-200202000-00013 | PMID 11791012 | https://pubmed.ncbi.nlm.nih.gov/11791012/ | https://doi.org/10.1097/00005344-200202000-00013
primary_references
Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats. | 2012 | DOI 10.1007/s10620-012-2155-y | PMID 22476587 | https://pubmed.ncbi.nlm.nih.gov/22476587/ | https://doi.org/10.1007/s10620-012-2155-y
source_locator
Reviewed reference lines 57-57; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 57–57
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Editorial identity/scope connection, not experimental causation. · Recorded from source · Recorded from source
**Derivatives keep their own outcomes.** Triacetylshikimic acid (TSA) reduced stimulated platelet aggregation and shunt thrombosis in rat experiments; reported cAMP increased, while cGMP, thromboxane/prostacyclin metabolites and clotting-time endpoints included null results. Those results are not assigned to parent shikimic acid. The separately tested 3,4-O-isopropylidene derivative (ISA) has rodent inflammatory/pain studies and cell-free radical-scavenging assays. Structural similarity does not establish interchangeable pharmacokinetics, targets or safety. [Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats.](https://pubmed.ncbi.nlm.nih.gov/11791012/) [Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats.](https://pubmed.ncbi.nlm.nih.gov/22476587/) [Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid.](https://pubmed.ncbi.nlm.nih.gov/27609150/)
Complete structured claim and evidence
The isopropylidene-shikimic-acid record is a distinct-compound or preparation comparison; its biological effects are not assigned to isolated shikimic acid.
Shikimic acid → 3,4-O-Isopropylidene shikimic acid / ISA Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Editorial identity/scope connection, not experimental causation.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Unsigned navigation, not a human metabolic conversion or automatic ingredient attribution.
plain_language
The isopropylidene-shikimic-acid record is a distinct-compound or preparation comparison; its biological effects are not assigned to isolated shikimic acid.
primary_references
Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid. | 2016 | DOI 10.3109/13880209.2016.1153663 | PMID 27609150 | https://pubmed.ncbi.nlm.nih.gov/27609150/ | https://doi.org/10.3109/13880209.2016.1153663
primary_references
Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats. | 2002 | DOI 10.1097/00005344-200202000-00013 | PMID 11791012 | https://pubmed.ncbi.nlm.nih.gov/11791012/ | https://doi.org/10.1097/00005344-200202000-00013
primary_references
Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats. | 2012 | DOI 10.1007/s10620-012-2155-y | PMID 22476587 | https://pubmed.ncbi.nlm.nih.gov/22476587/ | https://doi.org/10.1007/s10620-012-2155-y
source_locator
Reviewed reference lines 57-57; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 57–57
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Editorial identity/scope connection, not experimental causation. · Recorded from source · Recorded from source
**Derivatives keep their own outcomes.** Triacetylshikimic acid (TSA) reduced stimulated platelet aggregation and shunt thrombosis in rat experiments; reported cAMP increased, while cGMP, thromboxane/prostacyclin metabolites and clotting-time endpoints included null results. Those results are not assigned to parent shikimic acid. The separately tested 3,4-O-isopropylidene derivative (ISA) has rodent inflammatory/pain studies and cell-free radical-scavenging assays. Structural similarity does not establish interchangeable pharmacokinetics, targets or safety. [Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats.](https://pubmed.ncbi.nlm.nih.gov/11791012/) [Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats.](https://pubmed.ncbi.nlm.nih.gov/22476587/) [Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid.](https://pubmed.ncbi.nlm.nih.gov/27609150/)
Complete structured claim and evidence
The oseltamivir record is a distinct-compound or preparation comparison; its biological effects are not assigned to isolated shikimic acid.
Shikimic acid → Oseltamivir Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted. Bibliographic manufacturing context retained from draft; publisher full text unavailable in this review. No synthesis instructions or newly verified experimental quantities extracted. Review article, manufacturing background only; not affirmative primary experimental support.
experimental_model
Editorial identity/scope connection, not experimental causation.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Unsigned navigation, not a human metabolic conversion or automatic ingredient attribution.
plain_language
The oseltamivir record is a distinct-compound or preparation comparison; its biological effects are not assigned to isolated shikimic acid.
primary_references
Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. | 1997 | DOI 10.1021/ja963036t | PMID 16526129 | https://pubmed.ncbi.nlm.nih.gov/16526129/ | https://doi.org/10.1021/ja963036t
primary_references
Metabolic engineering for microbial production of shikimic acid. | 2003 | DOI 10.1016/j.ymben.2003.09.001 | PMID 14642355 | https://pubmed.ncbi.nlm.nih.gov/14642355/ | https://doi.org/10.1016/j.ymben.2003.09.001
primary_references
Practical total synthesis of the anti-influenza drug GS-4104 | 1998 | DOI 10.1021/jo980330q | https://doi.org/10.1021/jo980330q
source_locator
Reviewed reference lines 43-43; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 43–43
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Editorial identity/scope connection, not experimental causation. · Recorded from source · Recorded from source
**A manufacturing precursor is not the finished drug.** Shikimic acid has served as a starting scaffold for chemical manufacture of oseltamivir. Adding the drug’s other functional groups requires chemical synthesis; humans do not turn ingested shikimic acid into oseltamivir. Manufacturing and fermentation routes are industrial context, not antiviral evidence for shikimic acid. The 1997 neuraminidase-inhibitor chemistry paper and the 1998 practical synthesis report concern synthesized drug structures. [Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity.](https://pubmed.ncbi.nlm.nih.gov/16526129/) [Practical total synthesis of the anti-influenza drug GS-4104](https://doi.org/10.1021/jo980330q) [Metabolic engineering for microbial production of shikimic acid.](https://pubmed.ncbi.nlm.nih.gov/14642355/)
Complete structured claim and evidence
The anisatin record is a distinct-compound or preparation comparison; its biological effects are not assigned to isolated shikimic acid.
Shikimic acid → Anisatin Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.
experimental_model
Editorial identity/scope connection, not experimental causation.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Unsigned navigation, not a human metabolic conversion or automatic ingredient attribution.
plain_language
The anisatin record is a distinct-compound or preparation comparison; its biological effects are not assigned to isolated shikimic acid.
primary_references
Anisatin modulation of the gamma-aminobutyric acid receptor-channel in rat dorsal root ganglion neurons. | 1999 | DOI 10.1038/sj.bjp.0702700 | PMID 10455311 | https://pubmed.ncbi.nlm.nih.gov/10455311/ | https://doi.org/10.1038/sj.bjp.0702700 | https://pmc.ncbi.nlm.nih.gov/articles/PMC1566146/
primary_references
Neurotoxicities in infants seen with the consumption of star anise tea. | 2004 | DOI 10.1542/peds.2004-0058 | PMID 15492355 | https://pubmed.ncbi.nlm.nih.gov/15492355/ | https://doi.org/10.1542/peds.2004-0058
source_locator
Reviewed reference lines 89-89; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 89–89
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Editorial identity/scope connection, not experimental causation. · Recorded from source · Recorded from source
**Star-anise toxicity is a preparation-identity issue.** Anisatin inhibited GABA-activated currents in rat dorsal-root-ganglion neurons in a use-dependent fashion; an estimated EC50 was 1.10 µM. It is a different molecule from shikimic acid. Seven infant neurological cases associated with star-anise tea and evidence of toxic species contamination demonstrate preparation risk, not toxicity attributable specifically to purified shikimic acid. Botanical identity, plant part, contamination, extraction and measured composition cannot be inferred from the name star anise. [Anisatin modulation of the gamma-aminobutyric acid receptor-channel in rat dorsal root ganglion neurons.](https://pubmed.ncbi.nlm.nih.gov/10455311/) [Neurotoxicities in infants seen with the consumption of star anise tea.](https://pubmed.ncbi.nlm.nih.gov/15492355/)
Complete structured claim and evidence
The shikimic-acid-prunus-patch-2026 record is a distinct-compound or preparation comparison; its biological effects are not assigned to isolated shikimic acid.
Shikimic acid → 2026 mixed shikimic-acid/Prunus-mume acne patch Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text methods/results reviewed. Published January 2026 despite 2025 in DOI.
experimental_model
Editorial identity/scope connection, not experimental causation.
interpretation_status
Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
limitations
Unsigned navigation, not a human metabolic conversion or automatic ingredient attribution.
plain_language
The shikimic-acid-prunus-patch-2026 record is a distinct-compound or preparation comparison; its biological effects are not assigned to isolated shikimic acid.
primary_references
Novel prospectives of shikimic acid and Prunus mume extract for enhancing bioactivity on 5α-reductase and stability in cosmetic patches for acne treatment | 2026 | DOI 10.3389/fntpr.2025.1737986 | https://www.frontiersin.org/journals/natural-products/articles/10.3389/fntpr.2025.1737986/full
source_locator
Reviewed reference lines 83-83; exact primary location described in quoted passage where extracted.
Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026) · lines 83–83
Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Editorial identity/scope connection, not experimental causation. · Recorded from source · Recorded from source
**A mixed patch does not isolate shikimic acid efficacy.** The same report studied patches containing 0.5% shikimic acid and 0.5% P. mume extract plus additional formulation constituents in 15 volunteers aged 18–28. It was open-label, nonrandomized and split-body, over 48 h. Sebum decreased with both this patch and a 0.5% salicylic-acid comparator; the between-patch difference was not significant (p=0.12). No adverse skin effects were reported in this small short study. It does not establish isolated shikimic acid efficacy, long-term safety, oral antiandrogen action or synergy. [Novel prospectives of shikimic acid and Prunus mume extract for enhancing bioactivity on 5α-reductase and stability in cosmetic patches for acne treatment](https://www.frontiersin.org/journals/natural-products/articles/10.3389/fntpr.2025.1737986/full)
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

Loss of both bacterial shikimate kinases changes nutrient dependence

Condition: machinery_impairment · Both E. coli AroK and AroL unavailable.

Normal role: Intact machinery supports the context-specific function described in the linked claims.

Recorded consequence: External aromatic amino acids become necessary for growth.