Rosmarinic acid

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA up to 10 mM", "comparator": "No RA", "endpoint": "RA did not significantly inhibit C3-convertase enzyme activity at concentrations up to 10 mM.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Purified complement system.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA did not significantly inhibit C3-convertase enzyme activity at concentrations up to 10 mM.

primary_references

Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. | https://pubmed.ncbi.nlm.nih.gov/10353266/ | https://doi.org/10.1016/s0006-2952(99)00044-1

source_locator

Reviewed reference ra-c3-convertase-null; This rules against calling the attachment result C3-convertase inhibition.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 221–227

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Purified complement system. · Recorded from source · Recorded from source

### ra-c3-convertase-null RA did not significantly inhibit C3-convertase enzyme activity at concentrations up to 10 mM. This rules against calling the attachment result C3-convertase inhibition. Model and exposure: Purified complement system. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. | 1999 | https://pubmed.ncbi.nlm.nih.gov/10353266/ | https://doi.org/10.1016/s0006-2952(99)00044-1 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA up to 10 mM", "comparator": "No RA", "endpoint": "RA up to 10 mM did not directly inactivate C3.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Human complement assay.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA up to 10 mM did not directly inactivate C3.

primary_references

Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. | https://pubmed.ncbi.nlm.nih.gov/10353266/ | https://doi.org/10.1016/s0006-2952(99)00044-1

source_locator

Reviewed reference ra-c3-inactivation-null;

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 245–251

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Human complement assay. · Recorded from source · Recorded from source

### ra-c3-inactivation-null RA up to 10 mM did not directly inactivate C3. Model and exposure: Human complement assay. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. | 1999 | https://pubmed.ncbi.nlm.nih.gov/10353266/ | https://doi.org/10.1016/s0006-2952(99)00044-1 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA during nascent C3b attachment", "comparator": "No RA", "endpoint": "RA inhibited covalent C3b attachment to surfaces with an IC50 of 34 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Purified human complement proteins and cells.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited covalent C3b attachment to surfaces with an IC50 of 34 micromolar.

primary_references

Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. | https://pubmed.ncbi.nlm.nih.gov/10353266/ | https://doi.org/10.1016/s0006-2952(99)00044-1

source_locator

Reviewed reference ra-c3b-attachment; Radiolabel entered the activated thioester-containing C3b chain, supporting direct interception.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 213–219

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Purified human complement proteins and cells. · Recorded from source · Recorded from source

### ra-c3b-attachment RA inhibited covalent C3b attachment to surfaces with an IC50 of 34 micromolar. Radiolabel entered the activated thioester-containing C3b chain, supporting direct interception. Model and exposure: Purified human complement proteins and cells. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. | 1999 | https://pubmed.ncbi.nlm.nih.gov/10353266/ | https://doi.org/10.1016/s0006-2952(99)00044-1 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA at high concentration", "comparator": "No RA", "endpoint": "C5-convertase inhibition required 1,500 micromolar RA in the tested system.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Purified complement assay.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

C5-convertase inhibition required 1,500 micromolar RA in the tested system.

primary_references

Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. | https://pubmed.ncbi.nlm.nih.gov/10353266/ | https://doi.org/10.1016/s0006-2952(99)00044-1

source_locator

Reviewed reference ra-c5-convertase-high; Much higher concentration than C3b-attachment inhibition; not oral human target engagement.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 229–235

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Purified complement assay. · Recorded from source · Recorded from source

### ra-c5-convertase-high C5-convertase inhibition required 1,500 micromolar RA in the tested system. Much higher concentration than C3b-attachment inhibition; not oral human target engagement. Model and exposure: Purified complement assay. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. | 1999 | https://pubmed.ncbi.nlm.nih.gov/10353266/ | https://doi.org/10.1016/s0006-2952(99)00044-1 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA", "comparator": "No RA", "endpoint": "RA inhibited classical- and alternative-pathway hemolysis at IC50 values of 180 and 160 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Human serum hemolytic assays.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited classical- and alternative-pathway hemolysis at IC50 values of 180 and 160 micromolar.

primary_references

Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. | https://pubmed.ncbi.nlm.nih.gov/10353266/ | https://doi.org/10.1016/s0006-2952(99)00044-1

source_locator

Reviewed reference ra-complement-lysis;

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 237–243

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Human serum hemolytic assays. · Recorded from source · Recorded from source

### ra-complement-lysis RA inhibited classical- and alternative-pathway hemolysis at IC50 values of 180 and 160 micromolar. Model and exposure: Human serum hemolytic assays. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. | 1999 | https://pubmed.ncbi.nlm.nih.gov/10353266/ | https://doi.org/10.1016/s0006-2952(99)00044-1 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Assay without RA", "endpoint": "RA inhibited COMT in the 2016 assay with an IC50 of 26.7 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Isolated RA from Blechnum brasiliense; enzyme species not specified in accessible abstract.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited COMT in the 2016 assay with an IC50 of 26.7 micromolar.

primary_references

Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. | https://pubmed.ncbi.nlm.nih.gov/27270453/ | https://doi.org/10.1016/j.cbi.2016.06.005

source_locator

Reviewed reference ra-comt-inhibition; Inhibition is distinct from RA methylation and from clinically meaningful endogenous-substrate competition.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 113–119

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Isolated RA from Blechnum brasiliense; enzyme species not specified in accessible abstract. · Recorded from source · Recorded from source

### ra-comt-inhibition RA inhibited COMT in the 2016 assay with an IC50 of 26.7 micromolar. Inhibition is distinct from RA methylation and from clinically meaningful endogenous-substrate competition. Model and exposure: Isolated RA from Blechnum brasiliense; enzyme species not specified in accessible abstract. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. | 2016 | https://pubmed.ncbi.nlm.nih.gov/27270453/ | https://doi.org/10.1016/j.cbi.2016.06.005 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_condition

No RA at the same Cu(II) 20 micromolar · Copper(II) ion Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

No RA at the same Cu(II) RA with Cu(II) · Rosmarinic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "RA with Cu(II)", "comparator": "No RA at the same Cu(II)", "endpoint": "RA plus Cu(II) increased isolated-DNA 8-oxodG and strand/base damage.", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "rosmarinic-acid", "state": "RA with Cu(II)"}, {"entity_slug": "copper-ii", "state": "20 micromolar"}]} Explicit extracted experimental comparison; recorded from source.

experimental_model

Isolated DNA; 20 micromolar CuCl2 or Fe(III)-EDTA, pH 7.8, 37 °C, 16 h. No intact human cells.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA plus Cu(II) increased isolated-DNA 8-oxodG and strand/base damage.

primary_references

Rosmarinic acid, a natural polyphenol, has a potential pro-oxidant risk via NADH-mediated oxidative DNA damage. | https://pubmed.ncbi.nlm.nih.gov/38831385/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC11149181/ | https://doi.org/10.1186/s41021-024-00307-7

source_locator

Reviewed reference ra-cu-dna; HPLC-ECD and labeled-fragment assays; not an oral-toxicity measurement.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 305–311

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Isolated DNA; 20 micromolar CuCl2 or Fe(III)-EDTA, pH 7.8, 37 °C, 16 h. No intact human cells. · Recorded from source · Recorded from source

### ra-cu-dna RA plus Cu(II) increased isolated-DNA 8-oxodG and strand/base damage. HPLC-ECD and labeled-fragment assays; not an oral-toxicity measurement. Model and exposure: Isolated DNA; 20 micromolar CuCl2 or Fe(III)-EDTA, pH 7.8, 37 °C, 16 h. No intact human cells. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Rosmarinic acid, a natural polyphenol, has a potential pro-oxidant risk via NADH-mediated oxidative DNA damage. | 2024 | https://pubmed.ncbi.nlm.nih.gov/38831385/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC11149181/ | https://doi.org/10.1186/s41021-024-00307-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA in rat microsomal assay", "comparator": "No inhibitor", "endpoint": "An older rat-liver microsomal study identified RA among inhibitors of iodothyronine deiodination.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

1984 microsomal preparation; dose-dependent in-vitro inhibition.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

An older rat-liver microsomal study identified RA among inhibitors of iodothyronine deiodination.

primary_references

Antihormonal effects of plant extracts: iodothyronine deiodinase of rat liver is inhibited by extracts and secondary metabolites of plants. | https://pubmed.ncbi.nlm.nih.gov/6724503/ | https://doi.org/10.1055/s-2007-1014739

source_locator

Reviewed reference ra-deiodination; The assay predates modern isoform classification. It does not establish direct molecular binding to DIO1 or dietary iodine/selenium depletion.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 518–524

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 1984 microsomal preparation; dose-dependent in-vitro inhibition. · Recorded from source · Recorded from source

### ra-deiodination An older rat-liver microsomal study identified RA among inhibitors of iodothyronine deiodination. The assay predates modern isoform classification. It does not establish direct molecular binding to DIO1 or dietary iodine/selenium depletion. Model and exposure: 1984 microsomal preparation; dose-dependent in-vitro inhibition. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Antihormonal effects of plant extracts: iodothyronine deiodinase of rat liver is inhibited by extracts and secondary metabolites of plants. | 1984 | https://pubmed.ncbi.nlm.nih.gov/6724503/ | https://doi.org/10.1055/s-2007-1014739 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Vehicle", "endpoint": "RA inhibited recombinant ERp57-dependent insulin reduction, IC50 176.82 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

2018 DTT-containing turbidity assay, 84 min; recombinant construct species not stated explicitly in Methods.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited recombinant ERp57-dependent insulin reduction, IC50 176.82 micromolar.

primary_references

Discovery of a Novel ERp57 Inhibitor as Antiplatelet Agent from Danshen <i>(Salvia miltiorrhiza)</i>. | https://pubmed.ncbi.nlm.nih.gov/29849736/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC5941821/ | https://doi.org/10.1155/2018/9387568

source_locator

Reviewed reference ra-erp57-assay; Docking contacts are predictions. Enzyme inhibition plus platelet inhibition does not alone prove ERp57 mediates the platelet effect.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 562–568

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 2018 DTT-containing turbidity assay, 84 min; recombinant construct species not stated explicitly in Methods. · Recorded from source · Recorded from source

### ra-erp57-assay RA inhibited recombinant ERp57-dependent insulin reduction, IC50 176.82 micromolar. Docking contacts are predictions. Enzyme inhibition plus platelet inhibition does not alone prove ERp57 mediates the platelet effect. Model and exposure: 2018 DTT-containing turbidity assay, 84 min; recombinant construct species not stated explicitly in Methods. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Discovery of a Novel ERp57 Inhibitor as Antiplatelet Agent from Danshen <i>(Salvia miltiorrhiza)</i>. | 2018 | https://pubmed.ncbi.nlm.nih.gov/29849736/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC5941821/ | https://doi.org/10.1155/2018/9387568 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_condition

Matched no-RA metal conditions RA with Fe(III)-EDTA, with/without NADH · Rosmarinic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

Matched no-RA metal conditions 20 micromolar · Iron(III)-EDTA assay complex Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "RA with Fe(III)-EDTA, with/without NADH", "comparator": "Matched no-RA metal conditions", "endpoint": "RA with Fe(III)-EDTA produced little 8-oxodG; NADH did not produce the copper-like increase.", "effect_direction": "no_detected_change", "combination": "joint", "conditions": [{"entity_slug": "rosmarinic-acid", "state": "RA with Fe(III)-EDTA, with/without NADH"}, {"entity_slug": "iron-iii-edta", "state": "20 micromolar"}]} Explicit extracted experimental comparison; recorded from source.

experimental_model

Isolated DNA; 20 micromolar CuCl2 or Fe(III)-EDTA, pH 7.8, 37 °C, 16 h. No intact human cells.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA with Fe(III)-EDTA produced little 8-oxodG; NADH did not produce the copper-like increase.

primary_references

Rosmarinic acid, a natural polyphenol, has a potential pro-oxidant risk via NADH-mediated oxidative DNA damage. | https://pubmed.ncbi.nlm.nih.gov/38831385/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC11149181/ | https://doi.org/10.1186/s41021-024-00307-7

source_locator

Reviewed reference ra-fe-null; A metal-speciation-specific null, not proof iron can never support RA oxidation.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 321–327

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Isolated DNA; 20 micromolar CuCl2 or Fe(III)-EDTA, pH 7.8, 37 °C, 16 h. No intact human cells. · Recorded from source · Recorded from source

### ra-fe-null RA with Fe(III)-EDTA produced little 8-oxodG; NADH did not produce the copper-like increase. A metal-speciation-specific null, not proof iron can never support RA oxidation. Model and exposure: Isolated DNA; 20 micromolar CuCl2 or Fe(III)-EDTA, pH 7.8, 37 °C, 16 h. No intact human cells. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Rosmarinic acid, a natural polyphenol, has a potential pro-oxidant risk via NADH-mediated oxidative DNA damage. | 2024 | https://pubmed.ncbi.nlm.nih.gov/38831385/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC11149181/ | https://doi.org/10.1186/s41021-024-00307-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_condition

Furosemide alone RA plus furosemide · Rosmarinic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

Furosemide alone 0.2 mg/kg IV · Furosemide Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "RA plus furosemide", "comparator": "Furosemide alone", "endpoint": "IV RA increased furosemide AUC from 1.52 to 3.30 micromolar h and reduced urinary excretion.", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "rosmarinic-acid", "state": "RA plus furosemide"}, {"entity_slug": "furosemide", "state": "0.2 mg/kg IV"}]} Explicit extracted experimental comparison; recorded from source.

experimental_model

Rats n=4/group; RA 10 mg/kg and furosemide 0.2 mg/kg IV.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

IV RA increased furosemide AUC from 1.52 to 3.30 micromolar h and reduced urinary excretion.

primary_references

Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083

source_locator

Reviewed reference ra-furosemide-exposure; OAT3 inhibition is a proposed contributor; transport and clinical diuresis are not the same endpoint.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 413–419

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Rats n=4/group; RA 10 mg/kg and furosemide 0.2 mg/kg IV. · Recorded from source · Recorded from source

### ra-furosemide-exposure IV RA increased furosemide AUC from 1.52 to 3.30 micromolar h and reduced urinary excretion. OAT3 inhibition is a proposed contributor; transport and clinical diuresis are not the same endpoint. Model and exposure: Rats n=4/group; RA 10 mg/kg and furosemide 0.2 mg/kg IV. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | 2021 | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "Purified RA at 100 micrograms/mL", "comparator": "No inhibitor", "endpoint": "RA inhibited rat-brain GABA-transaminase activity by about 40% at 100 micrograms/mL, approximately 278 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Bioassay-guided lemon-balm fractionation; enzyme assay.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited rat-brain GABA-transaminase activity by about 40% at 100 micrograms/mL, approximately 278 micromolar.

primary_references

Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. | https://pubmed.ncbi.nlm.nih.gov/19165747/ | https://doi.org/10.1002/ptr.2712

source_locator

Reviewed reference ra-gabat; Ursolic and oleanolic acids were also active constituents; human brain exposure and GABA elevation were not established.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 441–447

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Bioassay-guided lemon-balm fractionation; enzyme assay. · Recorded from source · Recorded from source

### ra-gabat RA inhibited rat-brain GABA-transaminase activity by about 40% at 100 micrograms/mL, approximately 278 micromolar. Ursolic and oleanolic acids were also active constituents; human brain exposure and GABA elevation were not established. Model and exposure: Bioassay-guided lemon-balm fractionation; enzyme assay. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. | 2009 | https://pubmed.ncbi.nlm.nih.gov/19165747/ | https://doi.org/10.1002/ptr.2712 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "GI-model passage without added bacteria", "comparator": "Starting RA", "endpoint": "The GI model without added L. johnsonii did not hydrolyze RA detectably.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Rosemary extract exposed to model pH, bile salts and digestive enzymes.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

The GI model without added L. johnsonii did not hydrolyze RA detectably.

primary_references

Hydrolysis of rosmarinic acid from rosemary extract with esterases and Lactobacillus johnsonii in vitro and in a gastrointestinal model. | https://pubmed.ncbi.nlm.nih.gov/19658402/ | https://doi.org/10.1021/jf9014262

source_locator

Reviewed reference ra-gi-model-null; A negative digestion result limits universal claims that host digestive enzymes inevitably split RA.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 93–99

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Rosemary extract exposed to model pH, bile salts and digestive enzymes. · Recorded from source · Recorded from source

### ra-gi-model-null The GI model without added L. johnsonii did not hydrolyze RA detectably. A negative digestion result limits universal claims that host digestive enzymes inevitably split RA. Model and exposure: Rosemary extract exposed to model pH, bile salts and digestive enzymes. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Hydrolysis of rosmarinic acid from rosemary extract with esterases and Lactobacillus johnsonii in vitro and in a gastrointestinal model. | 2009 | https://pubmed.ncbi.nlm.nih.gov/19658402/ | https://doi.org/10.1021/jf9014262 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract only; author follow-up identifies RA among prior binding hits. Full 2021 text unavailable.; Primary author follow-up Introduction passages describing the previous HuD binding study; new folic-acid cell findings are not RA findings.

experimental_model

Virtual screening followed by STD-NMR; authors identify four hits.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

The HuD study and author follow-up identify RA among compounds showing STD-NMR evidence of HuD binding.

primary_references

Identification of Compounds Targeting HuD. Another Brick in the Wall of Neurodegenerative Disease Treatment. | https://pubmed.ncbi.nlm.nih.gov/34219450/ | https://doi.org/10.1021/acs.jmedchem.1c00191

primary_references

Short- and Long-Term Regulation of HuD: A Molecular Switch Mediated by Folic Acid? | https://pubmed.ncbi.nlm.nih.gov/37569576/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10418318/ | https://doi.org/10.3390/ijms241512201

source_locator

Reviewed reference ra-hud-binding; Binding is not functional inhibition. Folic-acid follow-up cell results are not RA results; RA clinical neuronal benefit remains untested.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 481–488

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Virtual screening followed by STD-NMR; authors identify four hits. · Recorded from source · Recorded from source

### ra-hud-binding The HuD study and author follow-up identify RA among compounds showing STD-NMR evidence of HuD binding. Binding is not functional inhibition. Folic-acid follow-up cell results are not RA results; RA clinical neuronal benefit remains untested. Model and exposure: Virtual screening followed by STD-NMR; authors identify four hits. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Identification of Compounds Targeting HuD. Another Brick in the Wall of Neurodegenerative Disease Treatment. | 2021 | https://pubmed.ncbi.nlm.nih.gov/34219450/ | https://doi.org/10.1021/acs.jmedchem.1c00191 | Access: Indexed primary abstract only; author follow-up identifies RA among prior binding hits. Full 2021 text unavailable. Reference: Short- and Long-Term Regulation of HuD: A Molecular Switch Mediated by Folic Acid? | 2023 | https://pubmed.ncbi.nlm.nih.gov/37569576/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10418318/ | https://doi.org/10.3390/ijms241512201 | Access: Primary author follow-up Introduction passages describing the previous HuD binding study; new folic-acid cell findings are not RA findings.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Assay without RA", "endpoint": "RA reduced hydroxyl-radical signal in the 2016 ra assay, IC50 29.4 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

2016 chemical assays; assay-specific endpoints.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA reduced hydroxyl-radical signal in the 2016 ra assay, IC50 29.4 micromolar.

primary_references

Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. | https://pubmed.ncbi.nlm.nih.gov/27270453/ | https://doi.org/10.1016/j.cbi.2016.06.005

source_locator

Reviewed reference ra-hydroxyl-assay; Radical-scavenging activity does not establish a selective protein target or net antioxidant effect in humans.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 590–596

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 2016 chemical assays; assay-specific endpoints. · Recorded from source · Recorded from source

### ra-hydroxyl-assay RA reduced hydroxyl-radical signal in the 2016 ra assay, IC50 29.4 micromolar. Radical-scavenging activity does not establish a selective protein target or net antioxidant effect in humans. Model and exposure: 2016 chemical assays; assay-specific endpoints. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. | 2016 | https://pubmed.ncbi.nlm.nih.gov/27270453/ | https://doi.org/10.1016/j.cbi.2016.06.005 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Official chemical identity record; not a clinical experiment.

experimental_model

Chemical identity: C18H16O8; 360.31 g/mol.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Rosmarinic acid contains two catechol rings, one ester linkage and one free carboxylic acid; it is not dicarboxylic.

primary_references

PubChem CID 5281792: Rosmarinic acid | https://pubchem.ncbi.nlm.nih.gov/compound/5281792

source_locator

Reviewed reference ra-identity; The ester joins caffeic acid to 3,4-dihydroxyphenyllactic acid.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 19–25

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Chemical identity: C18H16O8; 360.31 g/mol. · Recorded from source · Recorded from source

### ra-identity Rosmarinic acid contains two catechol rings, one ester linkage and one free carboxylic acid; it is not dicarboxylic. The ester joins caffeic acid to 3,4-dihydroxyphenyllactic acid. Model and exposure: Chemical identity: C18H16O8; 360.31 g/mol. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: PubChem CID 5281792: Rosmarinic acid | accessed 2026-10-10 | https://pubchem.ncbi.nlm.nih.gov/compound/5281792 | Access: Official chemical identity record; not a clinical experiment.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Probe assay without RA", "endpoint": "RA inhibited human CYP2E1 assay activity, IC50 61.0 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Human recombinant enzyme / liver microsome study; in-vitro probe-substrate assay.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited human CYP2E1 assay activity, IC50 61.0 micromolar.

primary_references

Metabolic interactions of rosmarinic acid with human cytochrome P450 monooxygenases and uridine diphosphate glucuronosyltransferases. | https://pubmed.ncbi.nlm.nih.gov/30466000/ | https://doi.org/10.1016/j.biopha.2018.11.040

source_locator

Reviewed reference ra-inhibits-cyp2e1; Competitive inhibition reported for this enzyme. Clinical interaction at oral exposure was not tested.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 193–199

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Human recombinant enzyme / liver microsome study; in-vitro probe-substrate assay. · Recorded from source · Recorded from source

### ra-inhibits-cyp2e1 RA inhibited human CYP2E1 assay activity, IC50 61.0 micromolar. Competitive inhibition reported for this enzyme. Clinical interaction at oral exposure was not tested. Model and exposure: Human recombinant enzyme / liver microsome study; in-vitro probe-substrate assay. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Metabolic interactions of rosmarinic acid with human cytochrome P450 monooxygenases and uridine diphosphate glucuronosyltransferases. | 2019 | https://pubmed.ncbi.nlm.nih.gov/30466000/ | https://doi.org/10.1016/j.biopha.2018.11.040 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Probe assay without RA", "endpoint": "RA inhibited human UGT1A1 assay activity, IC50 9.24 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Human recombinant enzyme / liver microsome study; in-vitro probe-substrate assay.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited human UGT1A1 assay activity, IC50 9.24 micromolar.

primary_references

Metabolic interactions of rosmarinic acid with human cytochrome P450 monooxygenases and uridine diphosphate glucuronosyltransferases. | https://pubmed.ncbi.nlm.nih.gov/30466000/ | https://doi.org/10.1016/j.biopha.2018.11.040

source_locator

Reviewed reference ra-inhibits-ugt1a1; Competitive inhibition reported for this enzyme. Clinical interaction at oral exposure was not tested.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 169–175

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Human recombinant enzyme / liver microsome study; in-vitro probe-substrate assay. · Recorded from source · Recorded from source

### ra-inhibits-ugt1a1 RA inhibited human UGT1A1 assay activity, IC50 9.24 micromolar. Competitive inhibition reported for this enzyme. Clinical interaction at oral exposure was not tested. Model and exposure: Human recombinant enzyme / liver microsome study; in-vitro probe-substrate assay. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Metabolic interactions of rosmarinic acid with human cytochrome P450 monooxygenases and uridine diphosphate glucuronosyltransferases. | 2019 | https://pubmed.ncbi.nlm.nih.gov/30466000/ | https://doi.org/10.1016/j.biopha.2018.11.040 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Probe assay without RA", "endpoint": "RA inhibited human UGT1A6 assay activity, IC50 19.1 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Human recombinant enzyme / liver microsome study; in-vitro probe-substrate assay.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited human UGT1A6 assay activity, IC50 19.1 micromolar.

primary_references

Metabolic interactions of rosmarinic acid with human cytochrome P450 monooxygenases and uridine diphosphate glucuronosyltransferases. | https://pubmed.ncbi.nlm.nih.gov/30466000/ | https://doi.org/10.1016/j.biopha.2018.11.040

source_locator

Reviewed reference ra-inhibits-ugt1a6; Competitive inhibition reported for this enzyme. Clinical interaction at oral exposure was not tested.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 177–183

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Human recombinant enzyme / liver microsome study; in-vitro probe-substrate assay. · Recorded from source · Recorded from source

### ra-inhibits-ugt1a6 RA inhibited human UGT1A6 assay activity, IC50 19.1 micromolar. Competitive inhibition reported for this enzyme. Clinical interaction at oral exposure was not tested. Model and exposure: Human recombinant enzyme / liver microsome study; in-vitro probe-substrate assay. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Metabolic interactions of rosmarinic acid with human cytochrome P450 monooxygenases and uridine diphosphate glucuronosyltransferases. | 2019 | https://pubmed.ncbi.nlm.nih.gov/30466000/ | https://doi.org/10.1016/j.biopha.2018.11.040 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Probe assay without RA", "endpoint": "RA inhibited human UGT2B7 assay activity, IC50 23.4 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Human recombinant enzyme / liver microsome study; in-vitro probe-substrate assay.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited human UGT2B7 assay activity, IC50 23.4 micromolar.

primary_references

Metabolic interactions of rosmarinic acid with human cytochrome P450 monooxygenases and uridine diphosphate glucuronosyltransferases. | https://pubmed.ncbi.nlm.nih.gov/30466000/ | https://doi.org/10.1016/j.biopha.2018.11.040

source_locator

Reviewed reference ra-inhibits-ugt2b7; Competitive inhibition reported for this enzyme. Clinical interaction at oral exposure was not tested.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 185–191

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Human recombinant enzyme / liver microsome study; in-vitro probe-substrate assay. · Recorded from source · Recorded from source

### ra-inhibits-ugt2b7 RA inhibited human UGT2B7 assay activity, IC50 23.4 micromolar. Competitive inhibition reported for this enzyme. Clinical interaction at oral exposure was not tested. Model and exposure: Human recombinant enzyme / liver microsome study; in-vitro probe-substrate assay. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Metabolic interactions of rosmarinic acid with human cytochrome P450 monooxygenases and uridine diphosphate glucuronosyltransferases. | 2019 | https://pubmed.ncbi.nlm.nih.gov/30466000/ | https://doi.org/10.1016/j.biopha.2018.11.040 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Assay without RA", "endpoint": "RA reduced lipid peroxidation in the 2016 ra assay, IC50 19.6 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

2016 chemical assays; assay-specific endpoints.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA reduced lipid peroxidation in the 2016 ra assay, IC50 19.6 micromolar.

primary_references

Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. | https://pubmed.ncbi.nlm.nih.gov/27270453/ | https://doi.org/10.1016/j.cbi.2016.06.005

source_locator

Reviewed reference ra-lipid-oxidation; Radical-scavenging activity does not establish a selective protein target or net antioxidant effect in humans.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 582–588

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 2016 chemical assays; assay-specific endpoints. · Recorded from source · Recorded from source

### ra-lipid-oxidation RA reduced lipid peroxidation in the 2016 ra assay, IC50 19.6 micromolar. Radical-scavenging activity does not establish a selective protein target or net antioxidant effect in humans. Model and exposure: 2016 chemical assays; assay-specific endpoints. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. | 2016 | https://pubmed.ncbi.nlm.nih.gov/27270453/ | https://doi.org/10.1016/j.cbi.2016.06.005 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "No RA", "endpoint": "RA inhibited MAO-A in vitro, IC50 50.1 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

2016 cell-free enzyme assay; species unresolved in accessible abstract.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited MAO-A in vitro, IC50 50.1 micromolar.

primary_references

Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. | https://pubmed.ncbi.nlm.nih.gov/27270453/ | https://doi.org/10.1016/j.cbi.2016.06.005

source_locator

Reviewed reference ra-maoa-inhibition; MAO-A inhibition was not time-dependent, consistent with reversibility. No human neuronal target engagement was measured.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 121–127

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 2016 cell-free enzyme assay; species unresolved in accessible abstract. · Recorded from source · Recorded from source

### ra-maoa-inhibition RA inhibited MAO-A in vitro, IC50 50.1 micromolar. MAO-A inhibition was not time-dependent, consistent with reversibility. No human neuronal target engagement was measured. Model and exposure: 2016 cell-free enzyme assay; species unresolved in accessible abstract. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. | 2016 | https://pubmed.ncbi.nlm.nih.gov/27270453/ | https://doi.org/10.1016/j.cbi.2016.06.005 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "No RA", "endpoint": "RA inhibited MAO-B in vitro, IC50 184.6 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

2016 cell-free enzyme assay; species unresolved in accessible abstract.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited MAO-B in vitro, IC50 184.6 micromolar.

primary_references

Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. | https://pubmed.ncbi.nlm.nih.gov/27270453/ | https://doi.org/10.1016/j.cbi.2016.06.005

source_locator

Reviewed reference ra-maob-inhibition; MAO-A inhibition was not time-dependent, consistent with reversibility. No human neuronal target engagement was measured.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 129–135

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 2016 cell-free enzyme assay; species unresolved in accessible abstract. · Recorded from source · Recorded from source

### ra-maob-inhibition RA inhibited MAO-B in vitro, IC50 184.6 micromolar. MAO-A inhibition was not time-dependent, consistent with reversibility. No human neuronal target engagement was measured. Model and exposure: 2016 cell-free enzyme assay; species unresolved in accessible abstract. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. | 2016 | https://pubmed.ncbi.nlm.nih.gov/27270453/ | https://doi.org/10.1016/j.cbi.2016.06.005 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA plus IgE activation", "comparator": "IgE activation without RA", "endpoint": "RA reduced the intracellular calcium response in IgE-activated rat RBL-2H3 cells.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

2024 RBL-2H3 study; primary abstract, dose/timing not extracted.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA reduced the intracellular calcium response in IgE-activated rat RBL-2H3 cells.

primary_references

Inhibitory effect of rosmarinic acid on IgE-trigged mast cell degranulation in vitro and in vivo. | https://pubmed.ncbi.nlm.nih.gov/38270683/ | https://doi.org/10.1007/s11033-023-09164-z

source_locator

Reviewed reference ra-mast-calcium; No directly verified Lyn/Syk target is assigned.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 261–267

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 2024 RBL-2H3 study; primary abstract, dose/timing not extracted. · Recorded from source · Recorded from source

### ra-mast-calcium RA reduced the intracellular calcium response in IgE-activated rat RBL-2H3 cells. No directly verified Lyn/Syk target is assigned. Model and exposure: 2024 RBL-2H3 study; primary abstract, dose/timing not extracted. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Inhibitory effect of rosmarinic acid on IgE-trigged mast cell degranulation in vitro and in vivo. | 2024 | https://pubmed.ncbi.nlm.nih.gov/38270683/ | https://doi.org/10.1007/s11033-023-09164-z | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA plus IgE activation", "comparator": "IgE activation without RA", "endpoint": "RA reduced histamine and beta-hexosaminidase release in IgE-activated rat RBL-2H3 cells.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

2024 RBL-2H3 study; primary abstract, dose/timing not extracted.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA reduced histamine and beta-hexosaminidase release in IgE-activated rat RBL-2H3 cells.

primary_references

Inhibitory effect of rosmarinic acid on IgE-trigged mast cell degranulation in vitro and in vivo. | https://pubmed.ncbi.nlm.nih.gov/38270683/ | https://doi.org/10.1007/s11033-023-09164-z

source_locator

Reviewed reference ra-mast-release; No directly verified Lyn/Syk target is assigned.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 253–259

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 2024 RBL-2H3 study; primary abstract, dose/timing not extracted. · Recorded from source · Recorded from source

### ra-mast-release RA reduced histamine and beta-hexosaminidase release in IgE-activated rat RBL-2H3 cells. No directly verified Lyn/Syk target is assigned. Model and exposure: 2024 RBL-2H3 study; primary abstract, dose/timing not extracted. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Inhibitory effect of rosmarinic acid on IgE-trigged mast cell degranulation in vitro and in vivo. | 2024 | https://pubmed.ncbi.nlm.nih.gov/38270683/ | https://doi.org/10.1007/s11033-023-09164-z | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA plus IgE activation", "comparator": "IgE activation without RA", "endpoint": "RA reduced excess ROS signal in IgE-activated rat RBL-2H3 cells.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

2024 RBL-2H3 study; primary abstract, dose/timing not extracted.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA reduced excess ROS signal in IgE-activated rat RBL-2H3 cells.

primary_references

Inhibitory effect of rosmarinic acid on IgE-trigged mast cell degranulation in vitro and in vivo. | https://pubmed.ncbi.nlm.nih.gov/38270683/ | https://doi.org/10.1007/s11033-023-09164-z

source_locator

Reviewed reference ra-mast-ros; No directly verified Lyn/Syk target is assigned.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 269–275

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 2024 RBL-2H3 study; primary abstract, dose/timing not extracted. · Recorded from source · Recorded from source

### ra-mast-ros RA reduced excess ROS signal in IgE-activated rat RBL-2H3 cells. No directly verified Lyn/Syk target is assigned. Model and exposure: 2024 RBL-2H3 study; primary abstract, dose/timing not extracted. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Inhibitory effect of rosmarinic acid on IgE-trigged mast cell degranulation in vitro and in vivo. | 2024 | https://pubmed.ncbi.nlm.nih.gov/38270683/ | https://doi.org/10.1007/s11033-023-09164-z | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA during challenge in pseudosterile mice", "comparator": "Challenged pseudosterile controls", "endpoint": "The protective RA response was lost in the pseudosterile mouse model.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Microbiota-depleted mice compared with the conventional-microbiota response.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

The protective RA response was lost in the pseudosterile mouse model.

primary_references

Rosmarinic acid alleviated intestinal barrier damage caused by <i>Escherichia coli</i> by regulating the gut microbiota and inhibiting the NF-κB signalling pathway in mice. | https://pubmed.ncbi.nlm.nih.gov/39540591/ | https://doi.org/10.1039/d4fo02654c

source_locator

Reviewed reference ra-microbiota-required; Supports microbiota dependence in this model; it does not identify one causal organism or prove human barrier repair.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 554–560

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Microbiota-depleted mice compared with the conventional-microbiota response. · Recorded from source · Recorded from source

### ra-microbiota-required The protective RA response was lost in the pseudosterile mouse model. Supports microbiota dependence in this model; it does not identify one causal organism or prove human barrier repair. Model and exposure: Microbiota-depleted mice compared with the conventional-microbiota response. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Rosmarinic acid alleviated intestinal barrier damage caused by <i>Escherichia coli</i> by regulating the gut microbiota and inhibiting the NF-κB signalling pathway in mice. | 2024 | https://pubmed.ncbi.nlm.nih.gov/39540591/ | https://doi.org/10.1039/d4fo02654c | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_model

Microsomal incubation, 60 min; cofactor and GSH trapping conditions.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Human liver microsomes generated RA glucuronides, including the major reported M8 pathway.

primary_references

Characterization of the metabolites of rosmarinic acid in human liver microsomes using liquid chromatography combined with electrospray ionization tandem mass spectrometry. | https://pubmed.ncbi.nlm.nih.gov/32012312/ | https://doi.org/10.1002/bmc.4806

source_locator

Reviewed reference ra-microsome-glucuronidation; Metabolites assigned by high-resolution LC-MS/MS.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 137–143

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Microsomal incubation, 60 min; cofactor and GSH trapping conditions. · Recorded from source · Recorded from source

### ra-microsome-glucuronidation Human liver microsomes generated RA glucuronides, including the major reported M8 pathway. Metabolites assigned by high-resolution LC-MS/MS. Model and exposure: Microsomal incubation, 60 min; cofactor and GSH trapping conditions. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Characterization of the metabolites of rosmarinic acid in human liver microsomes using liquid chromatography combined with electrospray ionization tandem mass spectrometry. | 2020 | https://pubmed.ncbi.nlm.nih.gov/32012312/ | https://doi.org/10.1002/bmc.4806 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_model

Human liver microsomes; M10–M14 and M6 assignments.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Microsomal RA hydroxylation products were assigned, with additional GSH adducts and a separate Michael-addition product.

primary_references

Characterization of the metabolites of rosmarinic acid in human liver microsomes using liquid chromatography combined with electrospray ionization tandem mass spectrometry. | https://pubmed.ncbi.nlm.nih.gov/32012312/ | https://doi.org/10.1002/bmc.4806

source_locator

Reviewed reference ra-microsome-hydroxylation; These are structural pathway assignments from trapping, not measured clinical injury.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 161–167

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Human liver microsomes; M10–M14 and M6 assignments. · Recorded from source · Recorded from source

### ra-microsome-hydroxylation Microsomal RA hydroxylation products were assigned, with additional GSH adducts and a separate Michael-addition product. These are structural pathway assignments from trapping, not measured clinical injury. Model and exposure: Human liver microsomes; M10–M14 and M6 assignments. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Characterization of the metabolites of rosmarinic acid in human liver microsomes using liquid chromatography combined with electrospray ionization tandem mass spectrometry. | 2020 | https://pubmed.ncbi.nlm.nih.gov/32012312/ | https://doi.org/10.1002/bmc.4806 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA plus challenge", "comparator": "Challenge without RA", "endpoint": "RA pretreatment reduced the E. coli-associated increases in serum TNF-alpha, IL-6 and IL-1beta.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Mouse 20 mg/kg oral RA for one week before intraperitoneal challenge.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA pretreatment reduced the E. coli-associated increases in serum TNF-alpha, IL-6 and IL-1beta.

primary_references

Rosmarinic acid alleviated intestinal barrier damage caused by <i>Escherichia coli</i> by regulating the gut microbiota and inhibiting the NF-κB signalling pathway in mice. | https://pubmed.ncbi.nlm.nih.gov/39540591/ | https://doi.org/10.1039/d4fo02654c

source_locator

Reviewed reference ra-mouse-cytokines; Measured inflammatory response; does not establish direct cytokine inhibition or a nutrient-deficiency rescue.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 614–620

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Mouse 20 mg/kg oral RA for one week before intraperitoneal challenge. · Recorded from source · Recorded from source

### ra-mouse-cytokines RA pretreatment reduced the E. coli-associated increases in serum TNF-alpha, IL-6 and IL-1beta. Measured inflammatory response; does not establish direct cytokine inhibition or a nutrient-deficiency rescue. Model and exposure: Mouse 20 mg/kg oral RA for one week before intraperitoneal challenge. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Rosmarinic acid alleviated intestinal barrier damage caused by <i>Escherichia coli</i> by regulating the gut microbiota and inhibiting the NF-κB signalling pathway in mice. | 2024 | https://pubmed.ncbi.nlm.nih.gov/39540591/ | https://doi.org/10.1039/d4fo02654c | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA pretreatment plus E. coli challenge", "comparator": "E. coli challenge alone", "endpoint": "RA was associated with reduced NF-kappa-B signaling in the bacterial-challenge mouse and epithelial-cell experiments.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Mouse gavage 20 mg/kg for one week; accompanying epithelial-cell pretreatment 6 h and bacterial challenge 3 h.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA was associated with reduced NF-kappa-B signaling in the bacterial-challenge mouse and epithelial-cell experiments.

primary_references

Rosmarinic acid alleviated intestinal barrier damage caused by <i>Escherichia coli</i> by regulating the gut microbiota and inhibiting the NF-κB signalling pathway in mice. | https://pubmed.ncbi.nlm.nih.gov/39540591/ | https://doi.org/10.1039/d4fo02654c

source_locator

Reviewed reference ra-mouse-inflammatory-signaling; Primary abstract; exact subunit and direct binding were not established.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 606–612

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Mouse gavage 20 mg/kg for one week; accompanying epithelial-cell pretreatment 6 h and bacterial challenge 3 h. · Recorded from source · Recorded from source

### ra-mouse-inflammatory-signaling RA was associated with reduced NF-kappa-B signaling in the bacterial-challenge mouse and epithelial-cell experiments. Primary abstract; exact subunit and direct binding were not established. Model and exposure: Mouse gavage 20 mg/kg for one week; accompanying epithelial-cell pretreatment 6 h and bacterial challenge 3 h. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Rosmarinic acid alleviated intestinal barrier damage caused by <i>Escherichia coli</i> by regulating the gut microbiota and inhibiting the NF-κB signalling pathway in mice. | 2024 | https://pubmed.ncbi.nlm.nih.gov/39540591/ | https://doi.org/10.1039/d4fo02654c | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA-treated challenge", "comparator": "Challenge without RA", "endpoint": "RA reduced passive cutaneous anaphylaxis and allergic ear edema in the mouse model.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Anti-DNP IgE / DNP-HSA challenge; primary abstract.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA reduced passive cutaneous anaphylaxis and allergic ear edema in the mouse model.

primary_references

Inhibitory effect of rosmarinic acid on IgE-trigged mast cell degranulation in vitro and in vivo. | https://pubmed.ncbi.nlm.nih.gov/38270683/ | https://doi.org/10.1007/s11033-023-09164-z

source_locator

Reviewed reference ra-mouse-pca; Separate animal endpoint from the rat-cell measurements.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 277–283

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Anti-DNP IgE / DNP-HSA challenge; primary abstract. · Recorded from source · Recorded from source

### ra-mouse-pca RA reduced passive cutaneous anaphylaxis and allergic ear edema in the mouse model. Separate animal endpoint from the rat-cell measurements. Model and exposure: Anti-DNP IgE / DNP-HSA challenge; primary abstract. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Inhibitory effect of rosmarinic acid on IgE-trigged mast cell degranulation in vitro and in vivo. | 2024 | https://pubmed.ncbi.nlm.nih.gov/38270683/ | https://doi.org/10.1007/s11033-023-09164-z | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA pretreatment plus bacterial challenge", "comparator": "Bacterial challenge alone", "endpoint": "RA pretreatment mitigated loss of ZO-1 expression during the E. coli challenge.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Mice: oral 20 mg/kg for one week before intraperitoneal challenge; accompanying mouse epithelial-cell experiments.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA pretreatment mitigated loss of ZO-1 expression during the E. coli challenge.

primary_references

Rosmarinic acid alleviated intestinal barrier damage caused by <i>Escherichia coli</i> by regulating the gut microbiota and inhibiting the NF-κB signalling pathway in mice. | https://pubmed.ncbi.nlm.nih.gov/39540591/ | https://doi.org/10.1039/d4fo02654c

source_locator

Reviewed reference ra-mouse-zo1; The abstract has contradictory permeability wording, so no quantitative permeability claim is assigned.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 546–552

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Mice: oral 20 mg/kg for one week before intraperitoneal challenge; accompanying mouse epithelial-cell experiments. · Recorded from source · Recorded from source

### ra-mouse-zo1 RA pretreatment mitigated loss of ZO-1 expression during the E. coli challenge. The abstract has contradictory permeability wording, so no quantitative permeability claim is assigned. Model and exposure: Mice: oral 20 mg/kg for one week before intraperitoneal challenge; accompanying mouse epithelial-cell experiments. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Rosmarinic acid alleviated intestinal barrier damage caused by <i>Escherichia coli</i> by regulating the gut microbiota and inhibiting the NF-κB signalling pathway in mice. | 2024 | https://pubmed.ncbi.nlm.nih.gov/39540591/ | https://doi.org/10.1039/d4fo02654c | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Assay without RA", "endpoint": "RA reduced nitric-oxide radical signal in the 2016 ra assay, IC50 140 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

2016 chemical assays; assay-specific endpoints.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA reduced nitric-oxide radical signal in the 2016 ra assay, IC50 140 micromolar.

primary_references

Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. | https://pubmed.ncbi.nlm.nih.gov/27270453/ | https://doi.org/10.1016/j.cbi.2016.06.005

source_locator

Reviewed reference ra-no-assay; Radical-scavenging activity does not establish a selective protein target or net antioxidant effect in humans.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 598–604

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 2016 chemical assays; assay-specific endpoints. · Recorded from source · Recorded from source

### ra-no-assay RA reduced nitric-oxide radical signal in the 2016 ra assay, IC50 140 micromolar. Radical-scavenging activity does not establish a selective protein target or net antioxidant effect in humans. Model and exposure: 2016 chemical assays; assay-specific endpoints. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. | 2016 | https://pubmed.ncbi.nlm.nih.gov/27270453/ | https://doi.org/10.1016/j.cbi.2016.06.005 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_contrast

{"intervention": "RA plus platelet agonist", "comparator": "Same agonist with vehicle", "endpoint": "RA reduced arachidonic-acid-, ADP- and collagen-induced aggregation in isolated rabbit platelet-rich plasma.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

1–100 micromolar RA, 5-min pretreatment, agonist-specific comparisons.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA reduced arachidonic-acid-, ADP- and collagen-induced aggregation in isolated rabbit platelet-rich plasma.

primary_references

Discovery of a Novel ERp57 Inhibitor as Antiplatelet Agent from Danshen <i>(Salvia miltiorrhiza)</i>. | https://pubmed.ncbi.nlm.nih.gov/29849736/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC5941821/ | https://doi.org/10.1155/2018/9387568

source_locator

Reviewed reference ra-rabbit-platelets; Agonists: AA 0.24 mM, ADP 9 micromolar, collagen 10 micrograms/mL. No oral human bleeding or anticoagulant-interaction trial.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 570–576

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 1–100 micromolar RA, 5-min pretreatment, agonist-specific comparisons. · Recorded from source · Recorded from source

### ra-rabbit-platelets RA reduced arachidonic-acid-, ADP- and collagen-induced aggregation in isolated rabbit platelet-rich plasma. Agonists: AA 0.24 mM, ADP 9 micromolar, collagen 10 micrograms/mL. No oral human bleeding or anticoagulant-interaction trial. Model and exposure: 1–100 micromolar RA, 5-min pretreatment, agonist-specific comparisons. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Discovery of a Novel ERp57 Inhibitor as Antiplatelet Agent from Danshen <i>(Salvia miltiorrhiza)</i>. | 2018 | https://pubmed.ncbi.nlm.nih.gov/29849736/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC5941821/ | https://doi.org/10.1155/2018/9387568 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Publisher-indexed primary Methods, Results and Table 2 read through web retrieval; local HTML download blocked.

experimental_model

Male rats, six per group; 0.625 mg/kg IV reference; LC-MS/MS.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Rat absolute oral bioavailability was 1.69%, 1.28% and 0.91% at 12.5, 25 and 50 mg/kg oral RA, respectively.

primary_references

Pharmacokinetics of rosmarinic acid in rats by LC-MS/MS: absolute bioavailability and dose proportionality | https://pubs.rsc.org/en/content/articlehtml/2017/ra/c6ra28237g

source_locator

Reviewed reference ra-rat-bioavailability; Table 2; dose-normalized oral versus IV AUC. These values are not established human bioavailability.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 27–33

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Male rats, six per group; 0.625 mg/kg IV reference; LC-MS/MS. · Recorded from source · Recorded from source

### ra-rat-bioavailability Rat absolute oral bioavailability was 1.69%, 1.28% and 0.91% at 12.5, 25 and 50 mg/kg oral RA, respectively. Table 2; dose-normalized oral versus IV AUC. These values are not established human bioavailability. Model and exposure: Male rats, six per group; 0.625 mg/kg IV reference; LC-MS/MS. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Pharmacokinetics of rosmarinic acid in rats by LC-MS/MS: absolute bioavailability and dose proportionality | 2017 | https://pubs.rsc.org/en/content/articlehtml/2017/ra/c6ra28237g | Access: Publisher-indexed primary Methods, Results and Table 2 read through web retrieval; local HTML download blocked.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "Unoxidized compound", "comparator": "No compound", "endpoint": "Unoxidized RA was inactive in the reported TSH-binding assay; activity emerged after auto-oxidation.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Same study; bovine TSH and human thyroid membranes.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Unoxidized RA was inactive in the reported TSH-binding assay; activity emerged after auto-oxidation.

primary_references

The active principles of plant extracts with antithyrotropic activity: oxidation products of derivatives of 3,4-dihydroxycinnamic acid. | https://pubmed.ncbi.nlm.nih.gov/3987612/ | https://doi.org/10.1210/endo-116-5-1677

source_locator

Reviewed reference ra-thyroid-unoxidized-null; The oxidation state is part of the experimental actor.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 502–508

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Same study; bovine TSH and human thyroid membranes. · Recorded from source · Recorded from source

### ra-thyroid-unoxidized-null Unoxidized RA was inactive in the reported TSH-binding assay; activity emerged after auto-oxidation. The oxidation state is part of the experimental actor. Model and exposure: Same study; bovine TSH and human thyroid membranes. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: The active principles of plant extracts with antithyrotropic activity: oxidation products of derivatives of 3,4-dihydroxycinnamic acid. | 1985 | https://pubmed.ncbi.nlm.nih.gov/3987612/ | https://doi.org/10.1210/endo-116-5-1677 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Probe uptake without RA", "endpoint": "RA inhibited human SLC22A6 probe-substrate transport, IC50 60.6 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Engineered HEK293 transporter versus mock cells; five-minute uptake.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited human SLC22A6 probe-substrate transport, IC50 60.6 micromolar.

primary_references

Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083

source_locator

Reviewed reference ra-transporter-slc22a6; Inhibition does not demonstrate that RA is transported by this protein.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 373–379

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Engineered HEK293 transporter versus mock cells; five-minute uptake. · Recorded from source · Recorded from source

### ra-transporter-slc22a6 RA inhibited human SLC22A6 probe-substrate transport, IC50 60.6 micromolar. Inhibition does not demonstrate that RA is transported by this protein. Model and exposure: Engineered HEK293 transporter versus mock cells; five-minute uptake. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | 2021 | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Probe uptake without RA", "endpoint": "RA inhibited human SLC22A8 probe-substrate transport, IC50 1.52 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Engineered HEK293 transporter versus mock cells; five-minute uptake.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited human SLC22A8 probe-substrate transport, IC50 1.52 micromolar.

primary_references

Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083

source_locator

Reviewed reference ra-transporter-slc22a8; Inhibition does not demonstrate that RA is transported by this protein.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 381–387

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Engineered HEK293 transporter versus mock cells; five-minute uptake. · Recorded from source · Recorded from source

### ra-transporter-slc22a8 RA inhibited human SLC22A8 probe-substrate transport, IC50 1.52 micromolar. Inhibition does not demonstrate that RA is transported by this protein. Model and exposure: Engineered HEK293 transporter versus mock cells; five-minute uptake. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | 2021 | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Probe uptake without RA", "endpoint": "RA inhibited human SLCO1B1 probe-substrate transport, IC50 74.8 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Engineered HEK293 transporter versus mock cells; five-minute uptake.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited human SLCO1B1 probe-substrate transport, IC50 74.8 micromolar.

primary_references

Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083

source_locator

Reviewed reference ra-transporter-slco1b1; Inhibition does not demonstrate that RA is transported by this protein.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 389–395

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Engineered HEK293 transporter versus mock cells; five-minute uptake. · Recorded from source · Recorded from source

### ra-transporter-slco1b1 RA inhibited human SLCO1B1 probe-substrate transport, IC50 74.8 micromolar. Inhibition does not demonstrate that RA is transported by this protein. Model and exposure: Engineered HEK293 transporter versus mock cells; five-minute uptake. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | 2021 | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_contrast

{"intervention": "RA concentration series", "comparator": "Probe uptake without RA", "endpoint": "RA inhibited human SLCO1B3 probe-substrate transport, IC50 91.3 micromolar.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Engineered HEK293 transporter versus mock cells; five-minute uptake.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA inhibited human SLCO1B3 probe-substrate transport, IC50 91.3 micromolar.

primary_references

Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083

source_locator

Reviewed reference ra-transporter-slco1b3; Inhibition does not demonstrate that RA is transported by this protein.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 397–403

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Engineered HEK293 transporter versus mock cells; five-minute uptake. · Recorded from source · Recorded from source

### ra-transporter-slco1b3 RA inhibited human SLCO1B3 probe-substrate transport, IC50 91.3 micromolar. Inhibition does not demonstrate that RA is transported by this protein. Model and exposure: Engineered HEK293 transporter versus mock cells; five-minute uptake. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | 2021 | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_condition

Valsartan alone RA plus valsartan · Rosmarinic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

Valsartan alone 3 mg/kg IV · Valsartan Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "RA plus valsartan", "comparator": "Valsartan alone", "endpoint": "Table 4 reports higher extrapolated valsartan C0 with RA, 25.8 versus 17.8 micromolar.", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "rosmarinic-acid", "state": "RA plus valsartan"}, {"entity_slug": "valsartan", "state": "3 mg/kg IV"}]} Explicit extracted experimental comparison; recorded from source.

experimental_model

Same IV rat study; significant table marker, unlike AUC.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Table 4 reports higher extrapolated valsartan C0 with RA, 25.8 versus 17.8 micromolar.

primary_references

Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083

source_locator

Reviewed reference ra-valsartan-c0; Endpoint-specific discrepancy from the broad negative summary is preserved.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 429–435

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Same IV rat study; significant table marker, unlike AUC. · Recorded from source · Recorded from source

### ra-valsartan-c0 Table 4 reports higher extrapolated valsartan C0 with RA, 25.8 versus 17.8 micromolar. Endpoint-specific discrepancy from the broad negative summary is preserved. Model and exposure: Same IV rat study; significant table marker, unlike AUC. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | 2021 | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_condition

Valsartan alone RA plus valsartan · Rosmarinic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

Valsartan alone 3 mg/kg IV · Valsartan Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "RA plus valsartan", "comparator": "Valsartan alone", "endpoint": "RA did not significantly change valsartan AUC or biliary excretion in the rat IV comparison.", "effect_direction": "no_detected_change", "combination": "joint", "conditions": [{"entity_slug": "rosmarinic-acid", "state": "RA plus valsartan"}, {"entity_slug": "valsartan", "state": "3 mg/kg IV"}]} Explicit extracted experimental comparison; recorded from source.

experimental_model

RA 10 mg/kg plus valsartan 3 mg/kg IV; n=4.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA did not significantly change valsartan AUC or biliary excretion in the rat IV comparison.

primary_references

Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083

source_locator

Reviewed reference ra-valsartan-null; Table 4 nevertheless marks extrapolated C0 as increased; a broad statement of no PK changes would omit that result.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 421–427

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · RA 10 mg/kg plus valsartan 3 mg/kg IV; n=4. · Recorded from source · Recorded from source

### ra-valsartan-null RA did not significantly change valsartan AUC or biliary excretion in the rat IV comparison. Table 4 nevertheless marks extrapolated C0 as increased; a broad statement of no PK changes would omit that result. Model and exposure: RA 10 mg/kg plus valsartan 3 mg/kg IV; n=4. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | 2021 | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_model

HEK293 transfectants; 10 micromolar RA uptake for 5 min, plus concentration series.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Human OAT1 expression increased cellular RA uptake about 115-fold; measured Km was 26.5 micromolar.

primary_references

Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083

source_locator

Reviewed reference ra-oat1-uptake; Probenecid reduced uptake about 78%; other tested transporters did not show RA uptake above mock.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 365–371

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · HEK293 transfectants; 10 micromolar RA uptake for 5 min, plus concentration series. · Recorded from source · Recorded from source

### ra-oat1-uptake Human OAT1 expression increased cellular RA uptake about 115-fold; measured Km was 26.5 micromolar. Probenecid reduced uptake about 78%; other tested transporters did not show RA uptake above mock. Model and exposure: HEK293 transfectants; 10 micromolar RA uptake for 5 min, plus concentration series. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | 2021 | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_model

Concentration-dependent human liver microsome assays.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

The microsomal UGT system showed higher capacity and lower apparent affinity for RA metabolism than the phase-I system.

primary_references

Metabolic interactions of rosmarinic acid with human cytochrome P450 monooxygenases and uridine diphosphate glucuronosyltransferases. | https://pubmed.ncbi.nlm.nih.gov/30466000/ | https://doi.org/10.1016/j.biopha.2018.11.040

source_locator

Reviewed reference ra-ugt-metabolism; Specific recombinant enzymes supported RA disappearance; assay kinetics do not predict a clinical drug interaction alone.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 201–207

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Concentration-dependent human liver microsome assays. · Recorded from source · Recorded from source

### ra-ugt-metabolism The microsomal UGT system showed higher capacity and lower apparent affinity for RA metabolism than the phase-I system. Specific recombinant enzymes supported RA disappearance; assay kinetics do not predict a clinical drug interaction alone. Model and exposure: Concentration-dependent human liver microsome assays. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Metabolic interactions of rosmarinic acid with human cytochrome P450 monooxygenases and uridine diphosphate glucuronosyltransferases. | 2019 | https://pubmed.ncbi.nlm.nih.gov/30466000/ | https://doi.org/10.1016/j.biopha.2018.11.040 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_contrast

{"intervention": "RA-rich lemon-balm extract", "comparator": "Placebo", "endpoint": "The small Alzheimer extract trial found no significant between-group cognitive improvement.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

23 randomized patients; 500 mg RA/day in extract for 24 weeks.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

The small Alzheimer extract trial found no significant between-group cognitive improvement.

primary_references

Safety and efficacy of Melissa officinalis extract containing rosmarinic acid in the prevention of Alzheimer's disease progression. | https://pubmed.ncbi.nlm.nih.gov/33122694/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7596544/ | https://doi.org/10.1038/s41598-020-73729-2

source_locator

Reviewed reference ra-alz-cognition-null; Safety/tolerability was primary; cognition was secondary.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 449–455

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 23 randomized patients; 500 mg RA/day in extract for 24 weeks. · Recorded from source · Recorded from source

### ra-alz-cognition-null The small Alzheimer extract trial found no significant between-group cognitive improvement. Safety/tolerability was primary; cognition was secondary. Model and exposure: 23 randomized patients; 500 mg RA/day in extract for 24 weeks. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Safety and efficacy of Melissa officinalis extract containing rosmarinic acid in the prevention of Alzheimer's disease progression. | 2020 | https://pubmed.ncbi.nlm.nih.gov/33122694/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7596544/ | https://doi.org/10.1038/s41598-020-73729-2 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_contrast

{"intervention": "RA-rich lemon-balm extract", "comparator": "Placebo", "endpoint": "NPI-Q improved by 0.5 points with extract and worsened by 0.7 with placebo at 24 weeks.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Same trial; secondary neuropsychiatric endpoint, P=0.012.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

NPI-Q improved by 0.5 points with extract and worsened by 0.7 with placebo at 24 weeks.

primary_references

Safety and efficacy of Melissa officinalis extract containing rosmarinic acid in the prevention of Alzheimer's disease progression. | https://pubmed.ncbi.nlm.nih.gov/33122694/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7596544/ | https://doi.org/10.1038/s41598-020-73729-2

source_locator

Reviewed reference ra-alz-npi; Does not establish cognitive disease modification.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 457–463

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Same trial; secondary neuropsychiatric endpoint, P=0.012. · Recorded from source · Recorded from source

### ra-alz-npi NPI-Q improved by 0.5 points with extract and worsened by 0.7 with placebo at 24 weeks. Does not establish cognitive disease modification. Model and exposure: Same trial; secondary neuropsychiatric endpoint, P=0.012. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Safety and efficacy of Melissa officinalis extract containing rosmarinic acid in the prevention of Alzheimer's disease progression. | 2020 | https://pubmed.ncbi.nlm.nih.gov/33122694/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7596544/ | https://doi.org/10.1038/s41598-020-73729-2 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_model

Bacterial preparation 25 mg/mL; RA 5 mg/mL; pH 7, 37 °C, 2 h for incubation.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

L. johnsonii NCC 533 hydrolyzed RA completely in the tested incubation and up to 99% in the GI model.

primary_references

Hydrolysis of rosmarinic acid from rosemary extract with esterases and Lactobacillus johnsonii in vitro and in a gastrointestinal model. | https://pubmed.ncbi.nlm.nih.gov/19658402/ | https://doi.org/10.1021/jf9014262

source_locator

Reviewed reference ra-bacterial-hydrolysis; In-vitro/GI-model finding, not a human-colon mass balance.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 85–91

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Bacterial preparation 25 mg/mL; RA 5 mg/mL; pH 7, 37 °C, 2 h for incubation. · Recorded from source · Recorded from source

### ra-bacterial-hydrolysis L. johnsonii NCC 533 hydrolyzed RA completely in the tested incubation and up to 99% in the GI model. In-vitro/GI-model finding, not a human-colon mass balance. Model and exposure: Bacterial preparation 25 mg/mL; RA 5 mg/mL; pH 7, 37 °C, 2 h for incubation. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Hydrolysis of rosmarinic acid from rosemary extract with esterases and Lactobacillus johnsonii in vitro and in a gastrointestinal model. | 2009 | https://pubmed.ncbi.nlm.nih.gov/19658402/ | https://doi.org/10.1021/jf9014262 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract plus publisher-indexed Results describing the porcine COMT/SAM methylated standard. Full Methods access unavailable.

experimental_model

Commercial porcine liver COMT and SAM; publisher-indexed Results.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Porcine COMT with SAM generated a methylated RA standard used to identify methyl-RA.

primary_references

Function of Plectranthus barbatus herbal tea as neuronal acetylcholinesterase inhibitor. | https://pubmed.ncbi.nlm.nih.gov/21779558/ | https://doi.org/10.1039/c0fo00070a

source_locator

Reviewed reference ra-comt-substrate; Demonstrates enzymatic methylation, not an in-vivo rate or pool depletion.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 105–111

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Commercial porcine liver COMT and SAM; publisher-indexed Results. · Recorded from source · Recorded from source

### ra-comt-substrate Porcine COMT with SAM generated a methylated RA standard used to identify methyl-RA. Demonstrates enzymatic methylation, not an in-vivo rate or pool depletion. Model and exposure: Commercial porcine liver COMT and SAM; publisher-indexed Results. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Function of Plectranthus barbatus herbal tea as neuronal acetylcholinesterase inhibitor. | 2011 | https://pubmed.ncbi.nlm.nih.gov/21779558/ | https://doi.org/10.1039/c0fo00070a | Access: Indexed primary abstract plus publisher-indexed Results describing the porcine COMT/SAM methylated standard. Full Methods access unavailable.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_model

Baseline and week 24; sampling generally 4–5 h after capsules; limit 0.0028 nM.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA was below the stated CSF detection limit at the sampled trial visits.

primary_references

Safety and efficacy of Melissa officinalis extract containing rosmarinic acid in the prevention of Alzheimer's disease progression. | https://pubmed.ncbi.nlm.nih.gov/33122694/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7596544/ | https://doi.org/10.1038/s41598-020-73729-2

source_locator

Reviewed reference ra-csf-detection; A negative sampled concentration is not proof of absent exposure at all earlier times.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 465–471

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Baseline and week 24; sampling generally 4–5 h after capsules; limit 0.0028 nM. · Recorded from source · Recorded from source

### ra-csf-detection RA was below the stated CSF detection limit at the sampled trial visits. A negative sampled concentration is not proof of absent exposure at all earlier times. Model and exposure: Baseline and week 24; sampling generally 4–5 h after capsules; limit 0.0028 nM. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Safety and efficacy of Melissa officinalis extract containing rosmarinic acid in the prevention of Alzheimer's disease progression. | 2020 | https://pubmed.ncbi.nlm.nih.gov/33122694/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7596544/ | https://doi.org/10.1038/s41598-020-73729-2 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_model

RA 5 mg/mL; enzyme 0.02 U/mg; pH 7, 40 °C, 2 h.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Fungal chlorogenate esterase hydrolyzed about 90% of extract RA in the reported in-vitro incubation.

primary_references

Hydrolysis of rosmarinic acid from rosemary extract with esterases and Lactobacillus johnsonii in vitro and in a gastrointestinal model. | https://pubmed.ncbi.nlm.nih.gov/19658402/ | https://doi.org/10.1021/jf9014262

source_locator

Reviewed reference ra-esterase-hydrolysis; The cleavage connects the same caffeic-acid identity used in other chapters.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 77–83

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · RA 5 mg/mL; enzyme 0.02 U/mg; pH 7, 40 °C, 2 h. · Recorded from source · Recorded from source

### ra-esterase-hydrolysis Fungal chlorogenate esterase hydrolyzed about 90% of extract RA in the reported in-vitro incubation. The cleavage connects the same caffeic-acid identity used in other chapters. Model and exposure: RA 5 mg/mL; enzyme 0.02 U/mg; pH 7, 40 °C, 2 h. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Hydrolysis of rosmarinic acid from rosemary extract with esterases and Lactobacillus johnsonii in vitro and in a gastrointestinal model. | 2009 | https://pubmed.ncbi.nlm.nih.gov/19658402/ | https://doi.org/10.1021/jf9014262 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "Hexyl rosmarinate", "comparator": "Luteolin comparator", "endpoint": "The synthetic hexyl RA ester inhibited alpha-glucosidase more strongly than the comparator luteolin in the reported assay.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

2019 ester-derivative study; accessible abstract does not specify enzyme species.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

The synthetic hexyl RA ester inhibited alpha-glucosidase more strongly than the comparator luteolin in the reported assay.

primary_references

Rosmarinic acid and its ester derivatives for enhancing antibacterial, α-glucosidase inhibitory, and lipid accumulation suppression activities. | https://pubmed.ncbi.nlm.nih.gov/31353663/ | https://doi.org/10.1111/jfbc.12719

source_locator

Reviewed reference ra-hexyl-glucosidase; Do not attribute this derivative result to parent RA or human intestinal brush-border enzymes.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 538–544

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 2019 ester-derivative study; accessible abstract does not specify enzyme species. · Recorded from source · Recorded from source

### ra-hexyl-glucosidase The synthetic hexyl RA ester inhibited alpha-glucosidase more strongly than the comparator luteolin in the reported assay. Do not attribute this derivative result to parent RA or human intestinal brush-border enzymes. Model and exposure: 2019 ester-derivative study; accessible abstract does not specify enzyme species. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Rosmarinic acid and its ester derivatives for enhancing antibacterial, α-glucosidase inhibitory, and lipid accumulation suppression activities. | 2019 | https://pubmed.ncbi.nlm.nih.gov/31353663/ | https://doi.org/10.1111/jfbc.12719 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract; publisher-linked erratum exists but its body was inaccessible. Corrected numerical details beyond the abstract are not verified.; Publisher identifies an erratum linked to the original paper. Correction body inaccessible; scope not independently verified.

experimental_model

Same six-person study; urine collected to 48 h.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Caffeic acid, ferulic acid and trace m-coumaric acid were detected in urine after the perilla preparation.

primary_references

Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans. | https://pubmed.ncbi.nlm.nih.gov/15309457/ | https://doi.org/10.1007/s00394-004-0482-2

primary_references

Erratum: Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans | https://link.springer.com/article/10.1007/s00394-004-0524-9

source_locator

Reviewed reference ra-human-degradation-products; RA-related urinary recovery was 6.3 ± 2.2% of dose. This is not a human absolute-bioavailability or intact-colon-delivery measurement.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 60–67

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Same six-person study; urine collected to 48 h. · Recorded from source · Recorded from source

### ra-human-degradation-products Caffeic acid, ferulic acid and trace m-coumaric acid were detected in urine after the perilla preparation. RA-related urinary recovery was 6.3 ± 2.2% of dose. This is not a human absolute-bioavailability or intact-colon-delivery measurement. Model and exposure: Same six-person study; urine collected to 48 h. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans. | 2005 | https://pubmed.ncbi.nlm.nih.gov/15309457/ | https://doi.org/10.1007/s00394-004-0482-2 | Access: Indexed primary abstract; publisher-linked erratum exists but its body was inaccessible. Corrected numerical details beyond the abstract are not verified. Reference: Erratum: Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans | 2005 | https://link.springer.com/article/10.1007/s00394-004-0524-9 | Access: Publisher identifies an erratum linked to the original paper. Correction body inaccessible; scope not independently verified.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_model

2015 human PK, Table 3.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

At the same 500-mg-RA extract dose, intact RA Cmax was 124.03 nM fasting and 85.95 nM fed.

primary_references

Pharmacokinetics, Safety and Tolerability of Melissa officinalis Extract which Contained Rosmarinic Acid in Healthy Individuals: A Randomized Controlled Trial. | https://pubmed.ncbi.nlm.nih.gov/25978046/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC4433273/ | https://doi.org/10.1371/journal.pone.0126422

source_locator

Reviewed reference ra-human-intact-exposure; Intact means unconjugated, not unbound. Fasting intact AUC0-48 was 228.77 nmol h/L; the abstract mislabels the total AUC of 832.13 as intact.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 43–49

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 2015 human PK, Table 3. · Recorded from source · Recorded from source

### ra-human-intact-exposure At the same 500-mg-RA extract dose, intact RA Cmax was 124.03 nM fasting and 85.95 nM fed. Intact means unconjugated, not unbound. Fasting intact AUC0-48 was 228.77 nmol h/L; the abstract mislabels the total AUC of 832.13 as intact. Model and exposure: 2015 human PK, Table 3. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Pharmacokinetics, Safety and Tolerability of Melissa officinalis Extract which Contained Rosmarinic Acid in Healthy Individuals: A Randomized Controlled Trial. | 2015 | https://pubmed.ncbi.nlm.nih.gov/25978046/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC4433273/ | https://doi.org/10.1371/journal.pone.0126422 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Indexed primary abstract; publisher-linked erratum exists but its body was inaccessible. Corrected numerical details beyond the abstract are not verified.; Publisher identifies an erratum linked to the original paper. Correction body inaccessible; scope not independently verified.

experimental_model

Six men; placebo crossover, 10-day interval; LC-MS.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Methylated RA appeared in human plasma and urine after perilla extract containing 200 mg RA.

primary_references

Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans. | https://pubmed.ncbi.nlm.nih.gov/15309457/ | https://doi.org/10.1007/s00394-004-0482-2

primary_references

Erratum: Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans | https://link.springer.com/article/10.1007/s00394-004-0524-9

source_locator

Reviewed reference ra-human-methyl-metabolite; Methyl-RA plasma Tmax 2 h; conjugated species predominated. Erratum body not recovered.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 51–58

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Six men; placebo crossover, 10-day interval; LC-MS. · Recorded from source · Recorded from source

### ra-human-methyl-metabolite Methylated RA appeared in human plasma and urine after perilla extract containing 200 mg RA. Methyl-RA plasma Tmax 2 h; conjugated species predominated. Erratum body not recovered. Model and exposure: Six men; placebo crossover, 10-day interval; LC-MS. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans. | 2005 | https://pubmed.ncbi.nlm.nih.gov/15309457/ | https://doi.org/10.1007/s00394-004-0482-2 | Access: Indexed primary abstract; publisher-linked erratum exists but its body was inaccessible. Corrected numerical details beyond the abstract are not verified. Reference: Erratum: Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans | 2005 | https://link.springer.com/article/10.1007/s00394-004-0524-9 | Access: Publisher identifies an erratum linked to the original paper. Correction body inaccessible; scope not independently verified.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_model

Healthy volunteers; six PK observations per condition, 11 participants across study arms.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Extract providing 500 mg RA produced total serum Cmax of 162.20 nM fasting and 142.20 nM fed.

primary_references

Pharmacokinetics, Safety and Tolerability of Melissa officinalis Extract which Contained Rosmarinic Acid in Healthy Individuals: A Randomized Controlled Trial. | https://pubmed.ncbi.nlm.nih.gov/25978046/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC4433273/ | https://doi.org/10.1371/journal.pone.0126422

source_locator

Reviewed reference ra-human-total-exposure; Table 3: median total Tmax 1 h fasting, 3 h fed. Total includes hydrolysable conjugates; neither Tmax is a half-life.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 35–41

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Healthy volunteers; six PK observations per condition, 11 participants across study arms. · Recorded from source · Recorded from source

### ra-human-total-exposure Extract providing 500 mg RA produced total serum Cmax of 162.20 nM fasting and 142.20 nM fed. Table 3: median total Tmax 1 h fasting, 3 h fed. Total includes hydrolysable conjugates; neither Tmax is a half-life. Model and exposure: Healthy volunteers; six PK observations per condition, 11 participants across study arms. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Pharmacokinetics, Safety and Tolerability of Melissa officinalis Extract which Contained Rosmarinic Acid in Healthy Individuals: A Randomized Controlled Trial. | 2015 | https://pubmed.ncbi.nlm.nih.gov/25978046/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC4433273/ | https://doi.org/10.1371/journal.pone.0126422 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "RA-rich lemon-balm extract", "comparator": "Placebo", "endpoint": "The 323-person trial found no significant overall cognitive advantage at 96 weeks.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Subjective or mild cognitive impairment; extract providing 500 mg RA/day; placebo-controlled, 24-week washout.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

The 323-person trial found no significant overall cognitive advantage at 96 weeks.

primary_references

Effects of Melissa officinalis Extract Containing Rosmarinic Acid on Cognition in Older Adults Without Dementia: A Randomized Controlled Trial. | https://pubmed.ncbi.nlm.nih.gov/36502333/ | https://doi.org/10.3233/jad-220953

source_locator

Reviewed reference ra-long-cognition-null; Nonhypertensive subgroup wording requires verification: the abstract-listed changes do not align with its favorable conclusion.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 473–479

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Subjective or mild cognitive impairment; extract providing 500 mg RA/day; placebo-controlled, 24-week washout. · Recorded from source · Recorded from source

### ra-long-cognition-null The 323-person trial found no significant overall cognitive advantage at 96 weeks. Nonhypertensive subgroup wording requires verification: the abstract-listed changes do not align with its favorable conclusion. Model and exposure: Subjective or mild cognitive impairment; extract providing 500 mg RA/day; placebo-controlled, 24-week washout. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Effects of Melissa officinalis Extract Containing Rosmarinic Acid on Cognition in Older Adults Without Dementia: A Randomized Controlled Trial. | 2023 | https://pubmed.ncbi.nlm.nih.gov/36502333/ | https://doi.org/10.3233/jad-220953 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_model

Human liver microsomes, LC-MS/MS; M7 to M9 assignment.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

An RA acylglucuronide pathway yielded an RA-S-acyl-GSH adduct in the reported metabolite analysis.

primary_references

Characterization of the metabolites of rosmarinic acid in human liver microsomes using liquid chromatography combined with electrospray ionization tandem mass spectrometry. | https://pubmed.ncbi.nlm.nih.gov/32012312/ | https://doi.org/10.1002/bmc.4806

source_locator

Reviewed reference ra-microsome-acylgsh; A distinct route from catechol oxidation.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 153–159

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Human liver microsomes, LC-MS/MS; M7 to M9 assignment. · Recorded from source · Recorded from source

### ra-microsome-acylgsh An RA acylglucuronide pathway yielded an RA-S-acyl-GSH adduct in the reported metabolite analysis. A distinct route from catechol oxidation. Model and exposure: Human liver microsomes, LC-MS/MS; M7 to M9 assignment. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Characterization of the metabolites of rosmarinic acid in human liver microsomes using liquid chromatography combined with electrospray ionization tandem mass spectrometry. | 2020 | https://pubmed.ncbi.nlm.nih.gov/32012312/ | https://doi.org/10.1002/bmc.4806 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_model

Human liver microsomes; 60-min incubation.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA oxidation products formed mono- and bis-glutathione adducts in microsomal trapping experiments.

primary_references

Characterization of the metabolites of rosmarinic acid in human liver microsomes using liquid chromatography combined with electrospray ionization tandem mass spectrometry. | https://pubmed.ncbi.nlm.nih.gov/32012312/ | https://doi.org/10.1002/bmc.4806

source_locator

Reviewed reference ra-microsome-quinone-trapping; Chemical assignments support reactive-intermediate trapping; neither intracellular GSH depletion nor toxicity was measured.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 145–151

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Human liver microsomes; 60-min incubation. · Recorded from source · Recorded from source

### ra-microsome-quinone-trapping RA oxidation products formed mono- and bis-glutathione adducts in microsomal trapping experiments. Chemical assignments support reactive-intermediate trapping; neither intracellular GSH depletion nor toxicity was measured. Model and exposure: Human liver microsomes; 60-min incubation. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Characterization of the metabolites of rosmarinic acid in human liver microsomes using liquid chromatography combined with electrospray ionization tandem mass spectrometry. | 2020 | https://pubmed.ncbi.nlm.nih.gov/32012312/ | https://doi.org/10.1002/bmc.4806 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "Enriched perilla regimen", "comparator": "Placebo", "endpoint": "RA-enriched perilla extract improved selected symptom responder rates versus placebo.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

29 mild-SAR patients, 21 days; reported RA-enriched 200-mg (n=10), 50-mg (n=9), placebo (n=10) groups.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA-enriched perilla extract improved selected symptom responder rates versus placebo.

primary_references

Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans. | https://pubmed.ncbi.nlm.nih.gov/14988517/ | https://doi.org/10.1177/153537020422900305

source_locator

Reviewed reference ra-perilla-allergy; Itchy nose, watery eyes, itchy eyes and total symptoms; not isolated RA or a demonstrated intracellular mediator.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 285–291

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 29 mild-SAR patients, 21 days; reported RA-enriched 200-mg (n=10), 50-mg (n=9), placebo (n=10) groups. · Recorded from source · Recorded from source

### ra-perilla-allergy RA-enriched perilla extract improved selected symptom responder rates versus placebo. Itchy nose, watery eyes, itchy eyes and total symptoms; not isolated RA or a demonstrated intracellular mediator. Model and exposure: 29 mild-SAR patients, 21 days; reported RA-enriched 200-mg (n=10), 50-mg (n=9), placebo (n=10) groups. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans. | 2004 | https://pubmed.ncbi.nlm.nih.gov/14988517/ | https://doi.org/10.1177/153537020422900305 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "Enriched perilla extract", "comparator": "Placebo", "endpoint": "Active perilla-extract treatment reduced nasal-lavage neutrophil and eosinophil counts.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Same 29-patient, 21-day trial.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Active perilla-extract treatment reduced nasal-lavage neutrophil and eosinophil counts.

primary_references

Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans. | https://pubmed.ncbi.nlm.nih.gov/14988517/ | https://doi.org/10.1177/153537020422900305

source_locator

Reviewed reference ra-perilla-nasal-cells; No adverse events or routine blood-test abnormalities were reported in this small trial. Oral administration did not directly bathe nasal tissue.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 293–299

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Same 29-patient, 21-day trial. · Recorded from source · Recorded from source

### ra-perilla-nasal-cells Active perilla-extract treatment reduced nasal-lavage neutrophil and eosinophil counts. No adverse events or routine blood-test abnormalities were reported in this small trial. Oral administration did not directly bathe nasal tissue. Model and exposure: Same 29-patient, 21-day trial. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans. | 2004 | https://pubmed.ncbi.nlm.nih.gov/14988517/ | https://doi.org/10.1177/153537020422900305 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

experimental_contrast

{"intervention": "IV RA plus probenecid", "comparator": "IV RA alone", "endpoint": "Probenecid co-injection increased rat RA AUC while reducing renal excretion.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Rat IV study; Table 2 and Figure 4.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Probenecid co-injection increased rat RA AUC while reducing renal excretion.

primary_references

Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083

source_locator

Reviewed reference ra-probenecid-exposure; Mechanistic support for anion-transporter-dependent elimination; not human oral exposure.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 405–411

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Rat IV study; Table 2 and Figure 4. · Recorded from source · Recorded from source

### ra-probenecid-exposure Probenecid co-injection increased rat RA AUC while reducing renal excretion. Mechanistic support for anion-transporter-dependent elimination; not human oral exposure. Model and exposure: Rat IV study; Table 2 and Figure 4. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid. | 2021 | https://pubmed.ncbi.nlm.nih.gov/33435470/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7828042/ | https://doi.org/10.3390/pharmaceutics13010083 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "Meal with rosemary extract", "comparator": "Identical meal without extract", "endpoint": "Rosemary phenolic-rich extract added to a meal reduced nonheme-iron absorption in women.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

14 women, ages 19–39; radiolabeled meals in ABBA/BAAB design.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Rosemary phenolic-rich extract added to a meal reduced nonheme-iron absorption in women.

primary_references

Green tea or rosemary extract added to foods reduces nonheme-iron absorption. | https://pubmed.ncbi.nlm.nih.gov/11237939/ | https://doi.org/10.1093/ajcn/73.3.607

source_locator

Reviewed reference ra-rosemary-iron; Extract-level outcome. Isolated RA contribution and clinical iron-deficiency incidence were not established.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 353–359

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 14 women, ages 19–39; radiolabeled meals in ABBA/BAAB design. · Recorded from source · Recorded from source

### ra-rosemary-iron Rosemary phenolic-rich extract added to a meal reduced nonheme-iron absorption in women. Extract-level outcome. Isolated RA contribution and clinical iron-deficiency incidence were not established. Model and exposure: 14 women, ages 19–39; radiolabeled meals in ABBA/BAAB design. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Green tea or rosemary extract added to foods reduces nonheme-iron absorption. | 2001 | https://pubmed.ncbi.nlm.nih.gov/11237939/ | https://doi.org/10.1093/ajcn/73.3.607 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_model

Healthy-human plasma and urine study; indexed primary abstract.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Human rosemary-tea study detected extensive conjugation and metabolite timing compatible with intestinal and colonic processing.

primary_references

Bioavailability and nutrikinetics of rosemary tea phenolic compounds in humans. | https://pubmed.ncbi.nlm.nih.gov/33509454/ | https://doi.org/10.1016/j.foodres.2020.109815

source_locator

Reviewed reference ra-tea-metabolites; Forty-eight compounds were identified. Total phenol recovery of 22.3% is not intact RA bioavailability.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 69–75

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Healthy-human plasma and urine study; indexed primary abstract. · Recorded from source · Recorded from source

### ra-tea-metabolites Human rosemary-tea study detected extensive conjugation and metabolite timing compatible with intestinal and colonic processing. Forty-eight compounds were identified. Total phenol recovery of 22.3% is not intact RA bioavailability. Model and exposure: Healthy-human plasma and urine study; indexed primary abstract. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Bioavailability and nutrikinetics of rosemary tea phenolic compounds in humans. | 2021 | https://pubmed.ncbi.nlm.nih.gov/33509454/ | https://doi.org/10.1016/j.foodres.2020.109815 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "Hormone preincubated with oxidized RA", "comparator": "Untreated hormone", "endpoint": "Preincubating bovine TSH with RA oxidation products reduced its activity in the mouse bioassay.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

Preincubation assay; not a controlled human oral RA trial.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

Preincubating bovine TSH with RA oxidation products reduced its activity in the mouse bioassay.

primary_references

The active principles of plant extracts with antithyrotropic activity: oxidation products of derivatives of 3,4-dihydroxycinnamic acid. | https://pubmed.ncbi.nlm.nih.gov/3987612/ | https://doi.org/10.1210/endo-116-5-1677

source_locator

Reviewed reference ra-thyroid-bioassay; This does not establish hypothyroidism or interference with levothyroxine treatment.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 510–516

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · Preincubation assay; not a controlled human oral RA trial. · Recorded from source · Recorded from source

### ra-thyroid-bioassay Preincubating bovine TSH with RA oxidation products reduced its activity in the mouse bioassay. This does not establish hypothyroidism or interference with levothyroxine treatment. Model and exposure: Preincubation assay; not a controlled human oral RA trial. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: The active principles of plant extracts with antithyrotropic activity: oxidation products of derivatives of 3,4-dihydroxycinnamic acid. | 1985 | https://pubmed.ncbi.nlm.nih.gov/3987612/ | https://doi.org/10.1210/endo-116-5-1677 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

evidence_access

Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.

experimental_contrast

{"intervention": "Auto-oxidized RA with bovine TSH", "comparator": "Hormone without oxidized compound", "endpoint": "RA auto-oxidation products inhibited bovine-TSH binding to human thyroid membranes.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; recorded from source.

experimental_model

1985 cell-free hormone-binding study; oxidation-product mixtures.

interpretation_status

Recorded from source with stated access limits; ungraded, not independent replication.

limitations

Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.

nutrient_topic

Rosmarinic acid collection; exact intervention and molecular form govern interpretation. · Rosmarinic acid

plain_language

RA auto-oxidation products inhibited bovine-TSH binding to human thyroid membranes.

primary_references

The active principles of plant extracts with antithyrotropic activity: oxidation products of derivatives of 3,4-dihydroxycinnamic acid. | https://pubmed.ncbi.nlm.nih.gov/3987612/ | https://doi.org/10.1210/endo-116-5-1677

source_locator

Reviewed reference ra-thyroid-oxidized; Across eight active compounds, half-inhibition required products equivalent to 20–80 micrograms/mL starting compound. No RA-specific universal clinical threshold.

Rosmarinic acid: detailed mechanisms of action (reviewed 10 October 2026) · lines 494–500

AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed. · supports · 1985 cell-free hormone-binding study; oxidation-product mixtures. · Recorded from source · Recorded from source

### ra-thyroid-oxidized RA auto-oxidation products inhibited bovine-TSH binding to human thyroid membranes. Across eight active compounds, half-inhibition required products equivalent to 20–80 micrograms/mL starting compound. No RA-specific universal clinical threshold. Model and exposure: 1985 cell-free hormone-binding study; oxidation-product mixtures. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: The active principles of plant extracts with antithyrotropic activity: oxidation products of derivatives of 3,4-dihydroxycinnamic acid. | 1985 | https://pubmed.ncbi.nlm.nih.gov/3987612/ | https://doi.org/10.1210/endo-116-5-1677 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.