Nutrient chapter

Berberine

Berberine is a plant protoberberine isoquinoline alkaloid studied as a pharmacological exposure, not an essential nutrient. Salt, formulation, dose, species, time and tissue are retained in claims. Human CYP inhibition and cyclosporine interactions are measured; many proposed metabolic benefits remain preclinical or population-specific.

98 recorded mechanisms · 5 availability situations · 5 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

Berberine increased the urinary dextromethorphan/dextrorphan ratio approximately ninefold, indicating reduced CYP2D6 activity.
Berberine → CYP2D6 activity measured by probe-drug phenotyping source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"}
experimental_model
Two-phase randomized crossover enzyme-phenotyping study
exposure
Berberine 300 mg three times daily for 14 days versus placebo
limitations
Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Healthy human male volunteers; 17 completed
plain_language
A human probe study measured slower metabolism through CYP2D6.
primary_references
[berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2
tissue_or_cell_type
Oral probe pharmacokinetics and urinary metabolite ratios
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 636–647
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-phase randomized crossover enzyme-phenotyping study · source_derived_draft · unverified_draft
### berberine-human-cyp-2d6 Berberine increased the urinary dextromethorphan/dextrorphan ratio approximately ninefold, indicating reduced CYP2D6 activity. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A human probe study measured slower metabolism through CYP2D6. organism: Healthy human male volunteers; 17 completed tissue_or_cell_type: Oral probe pharmacokinetics and urinary metabolite ratios experimental_model: Two-phase randomized crossover enzyme-phenotyping study limitations: Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence. exposure: Berberine 300 mg three times daily for 14 days versus placebo evidence_span: {"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"} [berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2
Complete structured claim and evidence
Repeated berberine inhibited CYP3A4 phenotypic activity, with midazolam oral clearance reduced by 27%.
Berberine → CYP3A4 activity measured by probe-drug phenotyping source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"}
experimental_model
Two-phase randomized crossover enzyme-phenotyping study
exposure
Berberine 300 mg three times daily for 14 days versus placebo
limitations
Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Healthy human male volunteers; 17 completed
plain_language
Drug clearance was measured, rather than inferred from gene expression.
primary_references
[berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2
tissue_or_cell_type
Oral probe pharmacokinetics and urinary metabolite ratios
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 662–673
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-phase randomized crossover enzyme-phenotyping study · source_derived_draft · unverified_draft
### berberine-human-cyp-3a4 Repeated berberine inhibited CYP3A4 phenotypic activity, with midazolam oral clearance reduced by 27%. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Drug clearance was measured, rather than inferred from gene expression. organism: Healthy human male volunteers; 17 completed tissue_or_cell_type: Oral probe pharmacokinetics and urinary metabolite ratios experimental_model: Two-phase randomized crossover enzyme-phenotyping study limitations: Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence. exposure: Berberine 300 mg three times daily for 14 days versus placebo evidence_span: {"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"} [berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2
Complete structured claim and evidence
Final cyclosporine concentrations were 29.3% higher in the berberine-treated group than in the group without berberine.
Berberine → Blood cyclosporine exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/16133554.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a86b1b0f9ad77889da596b013f9f229556d53d825dac1b8bb2ba6ed094a68ad", "start_char": 0, "end_char": 2232, "text_sha256": "7a86b1b0f9ad77889da596b013f9f229556d53d825dac1b8bb2ba6ed094a68ad"}
experimental_model
Randomized controlled transplant study with separate six-person pharmacokinetic arm
exposure
52 recipients per clinical arm; berberine 0.2 g three times daily for three months; six-person 12-day PK comparison
limitations
Observed interaction is clinically relevant, but the proposed CYP3A4 explanation was not uniquely established. Baseline change and between-group difference must not be confused.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Renal-transplant recipients
plain_language
A transplant medicine had higher blood concentrations with berberine.
primary_references
[berberine-p16133554] Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. (2005). https://pubmed.ncbi.nlm.nih.gov/16133554/ DOI: 10.1007/s00228-005-0952-3
tissue_or_cell_type
Cyclosporine blood concentrations
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 714–725
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled transplant study with separate six-person pharmacokinetic arm · source_derived_draft · unverified_draft
### berberine-cyclosporine-clinical Final cyclosporine concentrations were 29.3% higher in the berberine-treated group than in the group without berberine. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transplant medicine had higher blood concentrations with berberine. organism: Renal-transplant recipients tissue_or_cell_type: Cyclosporine blood concentrations experimental_model: Randomized controlled transplant study with separate six-person pharmacokinetic arm limitations: Observed interaction is clinically relevant, but the proposed CYP3A4 explanation was not uniquely established. Baseline change and between-group difference must not be confused. exposure: 52 recipients per clinical arm; berberine 0.2 g three times daily for three months; six-person 12-day PK comparison evidence_span: {"source_cache": "artifacts/berberine-research/16133554.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a86b1b0f9ad77889da596b013f9f229556d53d825dac1b8bb2ba6ed094a68ad", "start_char": 0, "end_char": 2232, "text_sha256": "7a86b1b0f9ad77889da596b013f9f229556d53d825dac1b8bb2ba6ed094a68ad"} [berberine-p16133554] Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. (2005). https://pubmed.ncbi.nlm.nih.gov/16133554/ DOI: 10.1007/s00228-005-0952-3
Complete structured claim and evidence
Berberine inhibited respiration in L6 myotubes and muscle mitochondria through a complex-I-associated effect.
Berberine → Mitochondrial respiratory complex I source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/18285556.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257", "start_char": 0, "end_char": 1735, "text_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257"}
experimental_model
Cell respiration, isolated mitochondria and kinase perturbation
exposure
Berberine concentration-response; kinase deletion/inhibition
limitations
Functional respiratory inhibition does not by itself establish direct binding to complex I or improved mitochondrial health. Preclinical exposure, not human efficacy.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Rat L6 myotubes, muscle mitochondria and LKB1-deficient cells
plain_language
Slowing one respiratory-chain step can trigger a cellular energy response.
primary_references
[berberine-p18285556] Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. (2008). https://pubmed.ncbi.nlm.nih.gov/18285556/ DOI: 10.2337/db07-1552
tissue_or_cell_type
Respiratory complex I and AMPK
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 324–335
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell respiration, isolated mitochondria and kinase perturbation · source_derived_draft · unverified_draft
### berberine-complex-i Berberine inhibited respiration in L6 myotubes and muscle mitochondria through a complex-I-associated effect. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Slowing one respiratory-chain step can trigger a cellular energy response. organism: Rat L6 myotubes, muscle mitochondria and LKB1-deficient cells tissue_or_cell_type: Respiratory complex I and AMPK experimental_model: Cell respiration, isolated mitochondria and kinase perturbation limitations: Functional respiratory inhibition does not by itself establish direct binding to complex I or improved mitochondrial health. Preclinical exposure, not human efficacy. exposure: Berberine concentration-response; kinase deletion/inhibition evidence_span: {"source_cache": "artifacts/berberine-research/18285556.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257", "start_char": 0, "end_char": 1735, "text_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257"} [berberine-p18285556] Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. (2008). https://pubmed.ncbi.nlm.nih.gov/18285556/ DOI: 10.2337/db07-1552
Complete structured claim and evidence
Berberine still increased glucose utilization after AMPK inhibition, AMPK-alpha silencing or dominant-negative AMPK expression.
Berberine → Cellular glucose consumption source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/25072399.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a", "start_char": 0, "end_char": 1385, "text_sha256": "aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a"}
experimental_model
Pharmacological inhibition, siRNA and dominant-negative AMPK experiments
exposure
Berberine concentration-response; 20 micromolar in phosphorylation experiments
limitations
AMPK is not necessary for every glucose response. This does not show that all other berberine actions are AMPK-independent; cell concentrations may exceed circulating parent drug.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human HepG2 hepatocytes and mouse C2C12 myotubes
plain_language
Cells can use more glucose even when this proposed signaling route is blocked.
primary_references
[berberine-p25072399] Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. (2014). https://pubmed.ncbi.nlm.nih.gov/25072399/ DOI: 10.1371/journal.pone.0103702
tissue_or_cell_type
Glucose consumption, lactate release and mitochondrial respiration
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 350–361
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pharmacological inhibition, siRNA and dominant-negative AMPK experiments · source_derived_draft · unverified_draft
### berberine-ampk-independent-glucose Berberine still increased glucose utilization after AMPK inhibition, AMPK-alpha silencing or dominant-negative AMPK expression. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells can use more glucose even when this proposed signaling route is blocked. organism: Human HepG2 hepatocytes and mouse C2C12 myotubes tissue_or_cell_type: Glucose consumption, lactate release and mitochondrial respiration experimental_model: Pharmacological inhibition, siRNA and dominant-negative AMPK experiments limitations: AMPK is not necessary for every glucose response. This does not show that all other berberine actions are AMPK-independent; cell concentrations may exceed circulating parent drug. exposure: Berberine concentration-response; 20 micromolar in phosphorylation experiments evidence_span: {"source_cache": "artifacts/berberine-research/25072399.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a", "start_char": 0, "end_char": 1385, "text_sha256": "aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a"} [berberine-p25072399] Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. (2014). https://pubmed.ncbi.nlm.nih.gov/25072399/ DOI: 10.1371/journal.pone.0103702
Complete structured claim and evidence
Berberine increased LDLR expression through an ERK-dependent, SREBP-independent post-transcriptional mechanism in human hepatoma cells.
Berberine → Human low-density lipoprotein receptor / LDLR source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/15531889.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac2a9817f85e5c1f4f520590f1f2cb1ca820cce75b79120852f616f7ce5bea2f", "start_char": 0, "end_char": 1032, "text_sha256": "ac2a9817f85e5c1f4f520590f1f2cb1ca820cce75b79120852f616f7ce5bea2f"}
experimental_model
Human hepatoma mRNA stability/promoter experiments, animal and small clinical arms
exposure
Berberine exposure with ERK-dependence assays
limitations
Clinical lipid outcomes do not directly prove this molecular route caused the human effect. Cell response was reported independent of SREBP.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human hepatoma cells for molecular claims
plain_language
More LDL receptor can help cells remove LDL from circulation; the mechanism was tested in cells.
primary_references
[berberine-p15531889] Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. (2004). https://pubmed.ncbi.nlm.nih.gov/15531889/ DOI: 10.1038/nm1135
tissue_or_cell_type
LDLR post-transcriptional regulation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 454–465
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human hepatoma mRNA stability/promoter experiments, animal and small clinical arms · source_derived_draft · unverified_draft
### berberine-ldlr-protein Berberine increased LDLR expression through an ERK-dependent, SREBP-independent post-transcriptional mechanism in human hepatoma cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: More LDL receptor can help cells remove LDL from circulation; the mechanism was tested in cells. organism: Human hepatoma cells for molecular claims tissue_or_cell_type: LDLR post-transcriptional regulation experimental_model: Human hepatoma mRNA stability/promoter experiments, animal and small clinical arms limitations: Clinical lipid outcomes do not directly prove this molecular route caused the human effect. Cell response was reported independent of SREBP. exposure: Berberine exposure with ERK-dependence assays evidence_span: {"source_cache": "artifacts/berberine-research/15531889.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac2a9817f85e5c1f4f520590f1f2cb1ca820cce75b79120852f616f7ce5bea2f", "start_char": 0, "end_char": 1032, "text_sha256": "ac2a9817f85e5c1f4f520590f1f2cb1ca820cce75b79120852f616f7ce5bea2f"} [berberine-p15531889] Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. (2004). https://pubmed.ncbi.nlm.nih.gov/15531889/ DOI: 10.1038/nm1135
Complete structured claim and evidence
Human OCT1 transported thiamine with approximately 9.5-fold lower affinity than mouse Oct1.
Human organic cation transporter 1 / OCT1 / SLC22A1 → Thiamine (vitamin B1) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/33037045.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61d53435dfc952ba419da91767e79c07d75e2a432d9d4a2afd0d8d2560d570fd", "start_char": 0, "end_char": 2298, "text_sha256": "61d53435dfc952ba419da91767e79c07d75e2a432d9d4a2afd0d8d2560d570fd"}
experimental_model
Human versus mouse transporter kinetics in transfected HEK293 cells
exposure
Thiamine and metformin transport; transporter chimeras
limitations
Human OCT1 affinity for thiamine was substantially lower than mouse Oct1. This is a shared-transporter connection, not proof berberine causes B1 deficiency.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human OCT1 and mouse Oct1
plain_language
Vitamin B1 shares this transporter, but the mouse and human versions behave differently.
primary_references
[berberine-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170
tissue_or_cell_type
Cellular thiamine uptake
transport_effect
raises A species-affinity comparison, but the measurement is thiamine carried into the expressing cell, which stands for the hepatocyte.
transport_pool
the hepatocyte interior A species-affinity comparison, but the measurement is thiamine carried into the expressing cell, which stands for the hepatocyte.
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 298–309
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human versus mouse transporter kinetics in transfected HEK293 cells · source_derived_draft · unverified_draft
### berberine-human-thiamine-transport Human OCT1 transported thiamine with approximately 9.5-fold lower affinity than mouse Oct1. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B1 shares this transporter, but the mouse and human versions behave differently. organism: Human OCT1 and mouse Oct1 tissue_or_cell_type: Cellular thiamine uptake experimental_model: Human versus mouse transporter kinetics in transfected HEK293 cells limitations: Human OCT1 affinity for thiamine was substantially lower than mouse Oct1. This is a shared-transporter connection, not proof berberine causes B1 deficiency. exposure: Thiamine and metformin transport; transporter chimeras evidence_span: {"source_cache": "artifacts/berberine-research/33037045.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61d53435dfc952ba419da91767e79c07d75e2a432d9d4a2afd0d8d2560d570fd", "start_char": 0, "end_char": 2298, "text_sha256": "61d53435dfc952ba419da91767e79c07d75e2a432d9d4a2afd0d8d2560d570fd"} [berberine-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170
Complete structured claim and evidence
Berberine inhibited choline-to-TMA conversion in bacterial cultures and gut consortia, including human fecal samples.
Berberine → Microbial conversion of choline to trimethylamine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"}
experimental_model
Choline tracer, microbial culture, microbiome transfer and atherosclerosis models
exposure
Choline-supplemented chow and berberine; deuterated choline tracing
limitations
Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia
plain_language
The nutrient choline has a microbial metabolic branch that berberine can influence.
primary_references
[berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
tissue_or_cell_type
Microbial choline metabolism
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1078–1089
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Choline tracer, microbial culture, microbiome transfer and atherosclerosis models · source_derived_draft · unverified_draft
### berberine-choline-tma Berberine inhibited choline-to-TMA conversion in bacterial cultures and gut consortia, including human fecal samples. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The nutrient choline has a microbial metabolic branch that berberine can influence. organism: C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia tissue_or_cell_type: Microbial choline metabolism experimental_model: Choline tracer, microbial culture, microbiome transfer and atherosclerosis models limitations: Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake. exposure: Choline-supplemented chow and berberine; deuterated choline tracing evidence_span: {"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"} [berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
Complete structured claim and evidence
Berberine decreased forskolin-stimulated chloride secretion in T84 monolayers through a predominantly PKC-alpha-dependent pathway.
Berberine → Colonic epithelial chloride secretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"}
experimental_model
Ussing-chamber short-circuit current, patch clamp and kinase perturbation
exposure
Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar
limitations
Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human T84 colonic cells
plain_language
The potassium-channel response is connected to movement of a different ion: chloride.
primary_references
[berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033
tissue_or_cell_type
Basolateral potassium recycling and chloride secretion
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 571–582
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ussing-chamber short-circuit current, patch clamp and kinase perturbation · source_derived_draft · unverified_draft
### berberine-chloride-secretion Berberine decreased forskolin-stimulated chloride secretion in T84 monolayers through a predominantly PKC-alpha-dependent pathway. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The potassium-channel response is connected to movement of a different ion: chloride. organism: Human T84 colonic cells tissue_or_cell_type: Basolateral potassium recycling and chloride secretion experimental_model: Ussing-chamber short-circuit current, patch clamp and kinase perturbation limitations: Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1. exposure: Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar evidence_span: {"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"} [berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033
Complete structured claim and evidence
HbA1c changed by -0.99 percentage points with berberine alone versus -0.59 with placebo over 12 weeks.
Berberine → Glycated hemoglobin / HbA1c concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/33024120.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9", "start_char": 0, "end_char": 1283, "text_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9"}
experimental_model
Multicenter randomized double-blind four-arm trial with metagenomics and microbial validation
exposure
Twelve weeks of berberine, probiotics, both or placebo after one week of gentamycin pretreatment
limitations
Antibiotic run-in and Chinese drug-naive population limit generalization. Microbial mediation is supported but not proof it explains every effect. Probiotic addition did not show a clear extra HbA1c reduction in the reported estimates.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
409 newly diagnosed type 2 diabetes patients; separate bacterial experiments
plain_language
The treatment difference was about 0.40 percentage points; the full within-group drop is not the placebo-adjusted effect.
primary_references
[berberine-p33024120] Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). (2020). https://pubmed.ncbi.nlm.nih.gov/33024120/ DOI: 10.1038/s41467-020-18414-8
tissue_or_cell_type
Glycemia, gut microbiome and bile-acid transformation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1130–1141
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter randomized double-blind four-arm trial with metagenomics and microbial validation · source_derived_draft · unverified_draft
### berberine-premote-hba1c HbA1c changed by -0.99 percentage points with berberine alone versus -0.59 with placebo over 12 weeks. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The treatment difference was about 0.40 percentage points; the full within-group drop is not the placebo-adjusted effect. organism: 409 newly diagnosed type 2 diabetes patients; separate bacterial experiments tissue_or_cell_type: Glycemia, gut microbiome and bile-acid transformation experimental_model: Multicenter randomized double-blind four-arm trial with metagenomics and microbial validation limitations: Antibiotic run-in and Chinese drug-naive population limit generalization. Microbial mediation is supported but not proof it explains every effect. Probiotic addition did not show a clear extra HbA1c reduction in the reported estimates. exposure: Twelve weeks of berberine, probiotics, both or placebo after one week of gentamycin pretreatment evidence_span: {"source_cache": "artifacts/berberine-research/33024120.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9", "start_char": 0, "end_char": 1283, "text_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9"} [berberine-p33024120] Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). (2020). https://pubmed.ncbi.nlm.nih.gov/33024120/ DOI: 10.1038/s41467-020-18414-8
Complete structured claim and evidence
Berberine did not reduce liver fat versus placebo; the between-group estimate was 0.9 percentage points with 97.5% CI -0.4 to 2.1.
Berberine → Liver fat content measured by imaging source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/41543854.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021", "start_char": 0, "end_char": 2354, "text_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021"}
experimental_model
Multicenter double-blind randomized placebo-controlled trial
exposure
Berberine 1 g/day for six months
limitations
No significant primary fat-reduction effect. Lipid endpoints were secondary; this population differs from diabetes trials and does not resolve every liver-disease subgroup.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
337 diabetes-free adults with obesity and MASLD in China
plain_language
A plausible metabolic mechanism did not produce this primary clinical outcome.
primary_references
[berberine-p41543854] Berberine and Adiposity in Diabetes-Free Individuals With Obesity and MASLD: A Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41543854/ DOI: 10.1001/jamanetworkopen.2025.54152
tissue_or_cell_type
CT visceral adipose area and liver fat; lipid endpoints
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1260–1271
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter double-blind randomized placebo-controlled trial · source_derived_draft · unverified_draft
### berberine-masld-liver-null Berberine did not reduce liver fat versus placebo; the between-group estimate was 0.9 percentage points with 97.5% CI -0.4 to 2.1. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A plausible metabolic mechanism did not produce this primary clinical outcome. organism: 337 diabetes-free adults with obesity and MASLD in China tissue_or_cell_type: CT visceral adipose area and liver fat; lipid endpoints experimental_model: Multicenter double-blind randomized placebo-controlled trial limitations: No significant primary fat-reduction effect. Lipid endpoints were secondary; this population differs from diabetes trials and does not resolve every liver-disease subgroup. exposure: Berberine 1 g/day for six months evidence_span: {"source_cache": "artifacts/berberine-research/41543854.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021", "start_char": 0, "end_char": 2354, "text_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021"} [berberine-p41543854] Berberine and Adiposity in Diabetes-Free Individuals With Obesity and MASLD: A Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41543854/ DOI: 10.1001/jamanetworkopen.2025.54152
Complete structured claim and evidence
Adenomas recurred in 36% of analyzed berberine participants versus 47% with placebo; relative risk 0.77, 95% CI 0.66-0.91.
Berberine → Colorectal adenoma recurrence source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/31926918.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0045a39cfd796c9db7aa81e0a9c4bea8004396e137d842519e03664560c4878c", "start_char": 0, "end_char": 2466, "text_sha256": "0045a39cfd796c9db7aa81e0a9c4bea8004396e137d842519e03664560c4878c"}
experimental_model
Multicenter double-blind randomized placebo-controlled trial
exposure
Berberine 0.3 g twice daily; colonoscopy follow-up up to two years
limitations
Modified intention-to-treat analysis excluded participants without efficacy data. Adenoma recurrence is not colorectal-cancer mortality or proof of cancer treatment.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Adults after colorectal polypectomy; 1108 randomized, 891 in full analysis
plain_language
A randomized study measured fewer recurrent polyps after their removal.
primary_references
[berberine-p31926918] Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study. (2020). https://pubmed.ncbi.nlm.nih.gov/31926918/ DOI: 10.1016/s2468-1253(19)30409-1
tissue_or_cell_type
Adenoma recurrence
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1299–1310
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter double-blind randomized placebo-controlled trial · source_derived_draft · unverified_draft
### berberine-adenoma-recurrence Adenomas recurred in 36% of analyzed berberine participants versus 47% with placebo; relative risk 0.77, 95% CI 0.66-0.91. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A randomized study measured fewer recurrent polyps after their removal. organism: Adults after colorectal polypectomy; 1108 randomized, 891 in full analysis tissue_or_cell_type: Adenoma recurrence experimental_model: Multicenter double-blind randomized placebo-controlled trial limitations: Modified intention-to-treat analysis excluded participants without efficacy data. Adenoma recurrence is not colorectal-cancer mortality or proof of cancer treatment. exposure: Berberine 0.3 g twice daily; colonoscopy follow-up up to two years evidence_span: {"source_cache": "artifacts/berberine-research/31926918.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0045a39cfd796c9db7aa81e0a9c4bea8004396e137d842519e03664560c4878c", "start_char": 0, "end_char": 2466, "text_sha256": "0045a39cfd796c9db7aa81e0a9c4bea8004396e137d842519e03664560c4878c"} [berberine-p31926918] Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study. (2020). https://pubmed.ncbi.nlm.nih.gov/31926918/ DOI: 10.1016/s2468-1253(19)30409-1
Complete structured claim and evidence
Gut bacterial nitroreductases converted berberine to dihydroberberine.
Gut bacterial nitroreductases, species and isoform not resolved → Berberine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/26174047.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e", "start_char": 0, "end_char": 1403, "text_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e"}
experimental_model
Bacterial enzyme, intestinal tissue, absorption and antibiotic-depletion experiments
exposure
Oral berberine, dihydroberberine and antibiotic pretreatment
limitations
Animal absorption difference is not a human bioavailability multiplier. Nitroreductases are unresolved bacterial enzyme families; no nitrogen-removal or vitamin-depletion mechanism inferred.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents including KK-Ay mice
plain_language
Gut microbes can change the chemical form before it is absorbed.
primary_references
[berberine-p26174047] Transforming berberine into its intestine-absorbable form by the gut microbiota. (2015). https://pubmed.ncbi.nlm.nih.gov/26174047/ DOI: 10.1038/srep12155
tissue_or_cell_type
Gut lumen, intestinal tissue and circulation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 142–153
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial enzyme, intestinal tissue, absorption and antibiotic-depletion experiments · source_derived_draft · unverified_draft
### berberine-microbial-reduction Gut bacterial nitroreductases converted berberine to dihydroberberine. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Gut microbes can change the chemical form before it is absorbed. organism: Gut bacteria and rodents including KK-Ay mice tissue_or_cell_type: Gut lumen, intestinal tissue and circulation experimental_model: Bacterial enzyme, intestinal tissue, absorption and antibiotic-depletion experiments limitations: Animal absorption difference is not a human bioavailability multiplier. Nitroreductases are unresolved bacterial enzyme families; no nitrogen-removal or vitamin-depletion mechanism inferred. exposure: Oral berberine, dihydroberberine and antibiotic pretreatment evidence_span: {"source_cache": "artifacts/berberine-research/26174047.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e", "start_char": 0, "end_char": 1403, "text_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e"} [berberine-p26174047] Transforming berberine into its intestine-absorbable form by the gut microbiota. (2015). https://pubmed.ncbi.nlm.nih.gov/26174047/ DOI: 10.1038/srep12155
Complete structured claim and evidence
Dihydroberberine had approximately fivefold greater intestinal absorption than berberine in the animal experiments.
Dihydroberberine → Berberine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/26174047.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e", "start_char": 0, "end_char": 1403, "text_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e"}
experimental_model
Bacterial enzyme, intestinal tissue, absorption and antibiotic-depletion experiments
exposure
Oral berberine, dihydroberberine and antibiotic pretreatment
limitations
Animal absorption difference is not a human bioavailability multiplier. Nitroreductases are unresolved bacterial enzyme families; no nitrogen-removal or vitamin-depletion mechanism inferred.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents including KK-Ay mice
plain_language
The reduced form crossed the intestinal barrier more readily in these animals.
primary_references
[berberine-p26174047] Transforming berberine into its intestine-absorbable form by the gut microbiota. (2015). https://pubmed.ncbi.nlm.nih.gov/26174047/ DOI: 10.1038/srep12155
tissue_or_cell_type
Gut lumen, intestinal tissue and circulation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 155–166
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial enzyme, intestinal tissue, absorption and antibiotic-depletion experiments · source_derived_draft · unverified_draft
### berberine-dhb-absorption Dihydroberberine had approximately fivefold greater intestinal absorption than berberine in the animal experiments. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reduced form crossed the intestinal barrier more readily in these animals. organism: Gut bacteria and rodents including KK-Ay mice tissue_or_cell_type: Gut lumen, intestinal tissue and circulation experimental_model: Bacterial enzyme, intestinal tissue, absorption and antibiotic-depletion experiments limitations: Animal absorption difference is not a human bioavailability multiplier. Nitroreductases are unresolved bacterial enzyme families; no nitrogen-removal or vitamin-depletion mechanism inferred. exposure: Oral berberine, dihydroberberine and antibiotic pretreatment evidence_span: {"source_cache": "artifacts/berberine-research/26174047.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e", "start_char": 0, "end_char": 1403, "text_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e"} [berberine-p26174047] Transforming berberine into its intestine-absorbable form by the gut microbiota. (2015). https://pubmed.ncbi.nlm.nih.gov/26174047/ DOI: 10.1038/srep12155
Complete structured claim and evidence
Intestinal tissues converted dihydroberberine back to berberine; heat inactivation did not prevent conversion, supporting a nonenzymatic oxidation process.
Dihydroberberine → Berberine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/26174047.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e", "start_char": 0, "end_char": 1403, "text_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e"}
experimental_model
Bacterial enzyme, intestinal tissue, absorption and antibiotic-depletion experiments
exposure
Oral berberine, dihydroberberine and antibiotic pretreatment
limitations
Animal absorption difference is not a human bioavailability multiplier. Nitroreductases are unresolved bacterial enzyme families; no nitrogen-removal or vitamin-depletion mechanism inferred.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents including KK-Ay mice
plain_language
The absorbed form can change back before appearing in blood.
primary_references
[berberine-p26174047] Transforming berberine into its intestine-absorbable form by the gut microbiota. (2015). https://pubmed.ncbi.nlm.nih.gov/26174047/ DOI: 10.1038/srep12155
tissue_or_cell_type
Gut lumen, intestinal tissue and circulation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 168–179
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial enzyme, intestinal tissue, absorption and antibiotic-depletion experiments · source_derived_draft · unverified_draft
### berberine-dhb-reoxidation Intestinal tissues converted dihydroberberine back to berberine; heat inactivation did not prevent conversion, supporting a nonenzymatic oxidation process. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The absorbed form can change back before appearing in blood. organism: Gut bacteria and rodents including KK-Ay mice tissue_or_cell_type: Gut lumen, intestinal tissue and circulation experimental_model: Bacterial enzyme, intestinal tissue, absorption and antibiotic-depletion experiments limitations: Animal absorption difference is not a human bioavailability multiplier. Nitroreductases are unresolved bacterial enzyme families; no nitrogen-removal or vitamin-depletion mechanism inferred. exposure: Oral berberine, dihydroberberine and antibiotic pretreatment evidence_span: {"source_cache": "artifacts/berberine-research/26174047.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e", "start_char": 0, "end_char": 1403, "text_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e"} [berberine-p26174047] Transforming berberine into its intestine-absorbable form by the gut microbiota. (2015). https://pubmed.ncbi.nlm.nih.gov/26174047/ DOI: 10.1038/srep12155
Complete structured claim and evidence
Antibiotic depletion reduced berberine-to-dihydroberberine conversion and blood berberine in KK-Ay mice.
Gut bacterial biomass → Plasma berberine exposure source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/berberine-research/26174047.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e", "start_char": 0, "end_char": 1403, "text_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e"}
experimental_model
Bacterial enzyme, intestinal tissue, absorption and antibiotic-depletion experiments
exposure
Oral berberine, dihydroberberine and antibiotic pretreatment
limitations
Animal absorption difference is not a human bioavailability multiplier. Nitroreductases are unresolved bacterial enzyme families; no nitrogen-removal or vitamin-depletion mechanism inferred.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents including KK-Ay mice
plain_language
Removing part of the processing system reduced absorption.
primary_references
[berberine-p26174047] Transforming berberine into its intestine-absorbable form by the gut microbiota. (2015). https://pubmed.ncbi.nlm.nih.gov/26174047/ DOI: 10.1038/srep12155
tissue_or_cell_type
Gut lumen, intestinal tissue and circulation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 181–192
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial enzyme, intestinal tissue, absorption and antibiotic-depletion experiments · source_derived_draft · unverified_draft
### berberine-bacteria-depletion Antibiotic depletion reduced berberine-to-dihydroberberine conversion and blood berberine in KK-Ay mice. Condition category: machinery_impairment nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing part of the processing system reduced absorption. organism: Gut bacteria and rodents including KK-Ay mice tissue_or_cell_type: Gut lumen, intestinal tissue and circulation experimental_model: Bacterial enzyme, intestinal tissue, absorption and antibiotic-depletion experiments limitations: Animal absorption difference is not a human bioavailability multiplier. Nitroreductases are unresolved bacterial enzyme families; no nitrogen-removal or vitamin-depletion mechanism inferred. exposure: Oral berberine, dihydroberberine and antibiotic pretreatment evidence_span: {"source_cache": "artifacts/berberine-research/26174047.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e", "start_char": 0, "end_char": 1403, "text_sha256": "17b12fa4d334225782db565c20fc34051522dafd77be442782aa82bd1ef34c9e"} [berberine-p26174047] Transforming berberine into its intestine-absorbable form by the gut microbiota. (2015). https://pubmed.ncbi.nlm.nih.gov/26174047/ DOI: 10.1038/srep12155
Complete structured claim and evidence
Human fecal nitroreductase activity correlated positively with blood berberine, with reported r=0.703.
Fecal bacterial nitroreductase activity → Plasma berberine exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/28744326.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d386d585993ca345f94fd99c5fbe0b209f6000fc10852db0a88621c03fc77830", "start_char": 0, "end_char": 1247, "text_sha256": "d386d585993ca345f94fd99c5fbe0b209f6000fc10852db0a88621c03fc77830"}
experimental_model
Dietary animal experiments and human observational pharmacokinetic comparison
exposure
High-fat diet in hamsters; oral berberine in animal and human arms
limitations
Human association does not validate fecal nitroreductase as a clinical dosing test. Diet, disease and microbial composition are potential covariates.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Hamsters, human hyperlipidemia patients and healthy participants
plain_language
Microbial processing may help explain why exposure differs between people.
primary_references
[berberine-p28744326] Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine. (2017). https://pubmed.ncbi.nlm.nih.gov/28744326/ DOI: 10.7150/thno.18290
tissue_or_cell_type
Fecal enzyme activity and blood berberine
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 194–205
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary animal experiments and human observational pharmacokinetic comparison · source_derived_draft · unverified_draft
### berberine-nitroreductase-marker Human fecal nitroreductase activity correlated positively with blood berberine, with reported r=0.703. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Microbial processing may help explain why exposure differs between people. organism: Hamsters, human hyperlipidemia patients and healthy participants tissue_or_cell_type: Fecal enzyme activity and blood berberine experimental_model: Dietary animal experiments and human observational pharmacokinetic comparison limitations: Human association does not validate fecal nitroreductase as a clinical dosing test. Diet, disease and microbial composition are potential covariates. exposure: High-fat diet in hamsters; oral berberine in animal and human arms evidence_span: {"source_cache": "artifacts/berberine-research/28744326.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d386d585993ca345f94fd99c5fbe0b209f6000fc10852db0a88621c03fc77830", "start_char": 0, "end_char": 1247, "text_sha256": "d386d585993ca345f94fd99c5fbe0b209f6000fc10852db0a88621c03fc77830"} [berberine-p28744326] Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine. (2017). https://pubmed.ncbi.nlm.nih.gov/28744326/ DOI: 10.7150/thno.18290
Complete structured claim and evidence
Human OCT1 transported berberine in transfected cells, with reported Km 14.8 micromolar.
Human organic cation transporter 1 / OCT1 / SLC22A1 → Berberine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/18157518.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b", "start_char": 0, "end_char": 1918, "text_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b"}
experimental_model
Polarized transporter-transfected MDCKII cells
exposure
Berberine transport kinetics and transporter inhibition
limitations
Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human OCT1, OCT2 and ABCB1 in engineered canine cells
plain_language
Berberine uses a separately identified organic-cation uptake transporter.
primary_references
[berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x
tissue_or_cell_type
Basolateral uptake and apical export
transport_effect
raises Berberine uptake measured in transfected cells, which stand for the hepatocyte, with a reported Km of 14.8 micromolar.
transport_pool
the hepatocyte interior Berberine uptake measured in transfected cells, which stand for the hepatocyte, with a reported Km of 14.8 micromolar.
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 207–218
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polarized transporter-transfected MDCKII cells · source_derived_draft · unverified_draft
### berberine-uptake-oct1 Human OCT1 transported berberine in transfected cells, with reported Km 14.8 micromolar. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Berberine uses a separately identified organic-cation uptake transporter. organism: Human OCT1, OCT2 and ABCB1 in engineered canine cells tissue_or_cell_type: Basolateral uptake and apical export experimental_model: Polarized transporter-transfected MDCKII cells limitations: Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck. exposure: Berberine transport kinetics and transporter inhibition evidence_span: {"source_cache": "artifacts/berberine-research/18157518.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b", "start_char": 0, "end_char": 1918, "text_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b"} [berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x
Complete structured claim and evidence
Human OCT2 transported berberine in transfected cells, with reported Km 4.4 micromolar.
Human organic cation transporter 2 / OCT2 / SLC22A2 → Berberine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/18157518.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b", "start_char": 0, "end_char": 1918, "text_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b"}
experimental_model
Polarized transporter-transfected MDCKII cells
exposure
Berberine transport kinetics and transporter inhibition
limitations
Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human OCT1, OCT2 and ABCB1 in engineered canine cells
plain_language
Berberine uses a separately identified organic-cation uptake transporter.
primary_references
[berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x
tissue_or_cell_type
Basolateral uptake and apical export
transport_effect
raises Berberine uptake measured in transfected cells, which stand for the tubular cell, with a reported Km of 4.4 micromolar.
transport_pool
the renal tubular cell interior Berberine uptake measured in transfected cells, which stand for the tubular cell, with a reported Km of 4.4 micromolar.
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 220–231
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polarized transporter-transfected MDCKII cells · source_derived_draft · unverified_draft
### berberine-uptake-oct2 Human OCT2 transported berberine in transfected cells, with reported Km 4.4 micromolar. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Berberine uses a separately identified organic-cation uptake transporter. organism: Human OCT1, OCT2 and ABCB1 in engineered canine cells tissue_or_cell_type: Basolateral uptake and apical export experimental_model: Polarized transporter-transfected MDCKII cells limitations: Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck. exposure: Berberine transport kinetics and transporter inhibition evidence_span: {"source_cache": "artifacts/berberine-research/18157518.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b", "start_char": 0, "end_char": 1918, "text_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b"} [berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x
Complete structured claim and evidence
OCT1/ABCB1 double-transfected cells transported berberine basolaterally to apically faster than single transfectants; zosuquidar inhibited apical efflux.
Human P-glycoprotein / ABCB1 / MDR1 → Berberine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/18157518.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b", "start_char": 0, "end_char": 1918, "text_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b"}
experimental_model
Polarized transporter-transfected MDCKII cells
exposure
Berberine transport kinetics and transporter inhibition
limitations
Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human OCT1, OCT2 and ABCB1 in engineered canine cells
plain_language
An entry transporter and an exit pump can work in sequence.
primary_references
[berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x
tissue_or_cell_type
Basolateral uptake and apical export
transport_effect
lowers Basolateral-to-apical flux exceeded absorptive flux and zosuquidar inhibited the apical efflux, so the step removes berberine from the cell.
transport_pool
the enterocyte interior Basolateral-to-apical flux exceeded absorptive flux and zosuquidar inhibited the apical efflux, so the step removes berberine from the cell.
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 233–244
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polarized transporter-transfected MDCKII cells · source_derived_draft · unverified_draft
### berberine-abcb1-efflux OCT1/ABCB1 double-transfected cells transported berberine basolaterally to apically faster than single transfectants; zosuquidar inhibited apical efflux. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An entry transporter and an exit pump can work in sequence. organism: Human OCT1, OCT2 and ABCB1 in engineered canine cells tissue_or_cell_type: Basolateral uptake and apical export experimental_model: Polarized transporter-transfected MDCKII cells limitations: Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck. exposure: Berberine transport kinetics and transporter inhibition evidence_span: {"source_cache": "artifacts/berberine-research/18157518.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b", "start_char": 0, "end_char": 1918, "text_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b"} [berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x
Complete structured claim and evidence
Berberine basolateral-to-apical flux exceeded absorptive flux by approximately 30-fold; P-glycoprotein substrates inhibited the secretory flux.
Human P-glycoprotein / ABCB1 / MDR1 → Berberine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/12434406.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489bc53e580f5a13cf3320ba724b6e83572a9f71f9eee9c2f1b255d7ebd26be2", "start_char": 0, "end_char": 1594, "text_sha256": "489bc53e580f5a13cf3320ba724b6e83572a9f71f9eee9c2f1b255d7ebd26be2"}
experimental_model
Bidirectional transport assays
exposure
Berberine transport and pretreatment
limitations
Caco-2 secretion is not a quantitative human drug-interaction study. Competing substrates implicate P-glycoprotein but do not make every substrate a clinical interaction.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human Caco-2 cells
plain_language
An intestinal efflux route can limit net absorption in the model.
primary_references
[berberine-p12434406] P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers. (2002). https://pubmed.ncbi.nlm.nih.gov/12434406/ DOI: 10.1002/jps.10268
tissue_or_cell_type
Intestinal epithelial model
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 246–257
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bidirectional transport assays · source_derived_draft · unverified_draft
### berberine-intestinal-efflux Berberine basolateral-to-apical flux exceeded absorptive flux by approximately 30-fold; P-glycoprotein substrates inhibited the secretory flux. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An intestinal efflux route can limit net absorption in the model. organism: Human Caco-2 cells tissue_or_cell_type: Intestinal epithelial model experimental_model: Bidirectional transport assays limitations: Caco-2 secretion is not a quantitative human drug-interaction study. Competing substrates implicate P-glycoprotein but do not make every substrate a clinical interaction. exposure: Berberine transport and pretreatment evidence_span: {"source_cache": "artifacts/berberine-research/12434406.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489bc53e580f5a13cf3320ba724b6e83572a9f71f9eee9c2f1b255d7ebd26be2", "start_char": 0, "end_char": 1594, "text_sha256": "489bc53e580f5a13cf3320ba724b6e83572a9f71f9eee9c2f1b255d7ebd26be2"} [berberine-p12434406] P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers. (2002). https://pubmed.ncbi.nlm.nih.gov/12434406/ DOI: 10.1002/jps.10268
Complete structured claim and evidence
Poor OCT1 transporters did not show a difference in human berberine pharmacokinetics despite reduced uptake by variant OCT1 in vitro.
Human organic cation transporter 1 / OCT1 / SLC22A1 → Plasma berberine exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/39488825.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33", "start_char": 0, "end_char": 1787, "text_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33"}
experimental_model
Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics
exposure
Oral berberine; OCT1 and CYP2D6 functional variants; sex-stratified analysis
limitations
Human OCT1 null finding differs from cellular and mouse findings. Sex-specific CYP2D6 result is not a universal rule for all formulations or a dosing algorithm.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human participants and human OCT1; Oct1/2-deficient mice in separate arms
plain_language
A cell-transport difference did not translate into a detected blood-level difference.
primary_references
[berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454
tissue_or_cell_type
Liver transport and systemic exposure
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 259–270
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics · source_derived_draft · unverified_draft
### berberine-oct1-genotype-null Poor OCT1 transporters did not show a difference in human berberine pharmacokinetics despite reduced uptake by variant OCT1 in vitro. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cell-transport difference did not translate into a detected blood-level difference. organism: Human participants and human OCT1; Oct1/2-deficient mice in separate arms tissue_or_cell_type: Liver transport and systemic exposure experimental_model: Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics limitations: Human OCT1 null finding differs from cellular and mouse findings. Sex-specific CYP2D6 result is not a universal rule for all formulations or a dosing algorithm. exposure: Oral berberine; OCT1 and CYP2D6 functional variants; sex-stratified analysis evidence_span: {"source_cache": "artifacts/berberine-research/39488825.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33", "start_char": 0, "end_char": 1787, "text_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33"} [berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454
Complete structured claim and evidence
Female CYP2D6 poor metabolizers had an 80% lower M1-to-berberine ratio; the genotype effect was not found in males.
Human cytochrome P450 2D6 → Berberine M1-to-parent metabolite ratio source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/39488825.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33", "start_char": 0, "end_char": 1787, "text_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33"}
experimental_model
Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics
exposure
Oral berberine; OCT1 and CYP2D6 functional variants; sex-stratified analysis
limitations
Human OCT1 null finding differs from cellular and mouse findings. Sex-specific CYP2D6 result is not a universal rule for all formulations or a dosing algorithm.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human participants and human OCT1; Oct1/2-deficient mice in separate arms
plain_language
The metabolic effect of this gene variant depended on sex in this study.
primary_references
[berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454
tissue_or_cell_type
Liver transport and systemic exposure
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 272–283
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics · source_derived_draft · unverified_draft
### berberine-cyp2d6-sex Female CYP2D6 poor metabolizers had an 80% lower M1-to-berberine ratio; the genotype effect was not found in males. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The metabolic effect of this gene variant depended on sex in this study. organism: Human participants and human OCT1; Oct1/2-deficient mice in separate arms tissue_or_cell_type: Liver transport and systemic exposure experimental_model: Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics limitations: Human OCT1 null finding differs from cellular and mouse findings. Sex-specific CYP2D6 result is not a universal rule for all formulations or a dosing algorithm. exposure: Oral berberine; OCT1 and CYP2D6 functional variants; sex-stratified analysis evidence_span: {"source_cache": "artifacts/berberine-research/39488825.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33", "start_char": 0, "end_char": 1787, "text_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33"} [berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454
Complete structured claim and evidence
Female participants had 2.8-fold higher berberine AUC and 3.6-fold higher Cmax than males; CYP2D6 explained only part of the difference.
Berberine → Plasma berberine exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/39488825.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33", "start_char": 0, "end_char": 1787, "text_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33"}
experimental_model
Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics
exposure
Oral berberine; OCT1 and CYP2D6 functional variants; sex-stratified analysis
limitations
Human OCT1 null finding differs from cellular and mouse findings. Sex-specific CYP2D6 result is not a universal rule for all formulations or a dosing algorithm.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human participants and human OCT1; Oct1/2-deficient mice in separate arms
plain_language
The same exposure can produce different blood levels across groups.
primary_references
[berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454
tissue_or_cell_type
Liver transport and systemic exposure
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 285–296
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics · source_derived_draft · unverified_draft
### berberine-sex-exposure Female participants had 2.8-fold higher berberine AUC and 3.6-fold higher Cmax than males; CYP2D6 explained only part of the difference. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same exposure can produce different blood levels across groups. organism: Human participants and human OCT1; Oct1/2-deficient mice in separate arms tissue_or_cell_type: Liver transport and systemic exposure experimental_model: Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics limitations: Human OCT1 null finding differs from cellular and mouse findings. Sex-specific CYP2D6 result is not a universal rule for all formulations or a dosing algorithm. exposure: Oral berberine; OCT1 and CYP2D6 functional variants; sex-stratified analysis evidence_span: {"source_cache": "artifacts/berberine-research/39488825.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33", "start_char": 0, "end_char": 1787, "text_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33"} [berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454
Complete structured claim and evidence
Oct1 deletion reduced hepatic thiamine-dependent enzyme activity, including pyruvate dehydrogenase, in mice.
Mouse organic cation transporter 1 / Oct1 → Mouse hepatic pyruvate dehydrogenase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/berberine-research/29659562.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10efb675e4e0cf5cea9c8607b6b2a5e3ad77c383f8b0a55efff5ed6d163be558", "start_char": 0, "end_char": 1652, "text_sha256": "10efb675e4e0cf5cea9c8607b6b2a5e3ad77c383f8b0a55efff5ed6d163be558"}
experimental_model
Mouse gene deletion and dietary depletion, with human genetic associations
exposure
Oct1 deletion or a thiamine-deficient diet
limitations
Mouse Oct1 deletion is not pharmacological berberine inhibition; human genetic associations do not establish berberine-induced thiamine depletion.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Mice for causal thiamine and PDH experiments
plain_language
A transporter can affect how the liver uses a vitamin-dependent fuel pathway.
primary_references
[berberine-p29659562] Organic cation transporter 1 (OCT1) modulates multiple cardiometabolic traits through effects on hepatic thiamine content. (2018). https://pubmed.ncbi.nlm.nih.gov/29659562/ DOI: 10.1371/journal.pbio.2002907
tissue_or_cell_type
Hepatic thiamine-dependent metabolism
trigger_kind
machinery_impairment Imported condition classification; unverified.
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 311–322
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse gene deletion and dietary depletion, with human genetic associations · source_derived_draft · unverified_draft
### berberine-oct1-pdh Oct1 deletion reduced hepatic thiamine-dependent enzyme activity, including pyruvate dehydrogenase, in mice. Condition category: machinery_impairment nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter can affect how the liver uses a vitamin-dependent fuel pathway. organism: Mice for causal thiamine and PDH experiments tissue_or_cell_type: Hepatic thiamine-dependent metabolism experimental_model: Mouse gene deletion and dietary depletion, with human genetic associations limitations: Mouse Oct1 deletion is not pharmacological berberine inhibition; human genetic associations do not establish berberine-induced thiamine depletion. exposure: Oct1 deletion or a thiamine-deficient diet evidence_span: {"source_cache": "artifacts/berberine-research/29659562.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10efb675e4e0cf5cea9c8607b6b2a5e3ad77c383f8b0a55efff5ed6d163be558", "start_char": 0, "end_char": 1652, "text_sha256": "10efb675e4e0cf5cea9c8607b6b2a5e3ad77c383f8b0a55efff5ed6d163be558"} [berberine-p29659562] Organic cation transporter 1 (OCT1) modulates multiple cardiometabolic traits through effects on hepatic thiamine content. (2018). https://pubmed.ncbi.nlm.nih.gov/29659562/ DOI: 10.1371/journal.pbio.2002907
Complete structured claim and evidence
Berberine increased AMPK phosphorylation in L6 myotubes.
Berberine → Rat AMP-activated protein kinase complexes source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/18285556.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257", "start_char": 0, "end_char": 1735, "text_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257"}
experimental_model
Cell respiration, isolated mitochondria and kinase perturbation
exposure
Berberine concentration-response; kinase deletion/inhibition
limitations
Functional respiratory inhibition does not by itself establish direct binding to complex I or improved mitochondrial health. Preclinical exposure, not human efficacy.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Rat L6 myotubes, muscle mitochondria and LKB1-deficient cells
plain_language
AMPK responds to the altered cellular energy state in this model.
primary_references
[berberine-p18285556] Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. (2008). https://pubmed.ncbi.nlm.nih.gov/18285556/ DOI: 10.2337/db07-1552
tissue_or_cell_type
Respiratory complex I and AMPK
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 337–348
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell respiration, isolated mitochondria and kinase perturbation · source_derived_draft · unverified_draft
### berberine-ampk Berberine increased AMPK phosphorylation in L6 myotubes. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: AMPK responds to the altered cellular energy state in this model. organism: Rat L6 myotubes, muscle mitochondria and LKB1-deficient cells tissue_or_cell_type: Respiratory complex I and AMPK experimental_model: Cell respiration, isolated mitochondria and kinase perturbation limitations: Functional respiratory inhibition does not by itself establish direct binding to complex I or improved mitochondrial health. Preclinical exposure, not human efficacy. exposure: Berberine concentration-response; kinase deletion/inhibition evidence_span: {"source_cache": "artifacts/berberine-research/18285556.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257", "start_char": 0, "end_char": 1735, "text_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257"} [berberine-p18285556] Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. (2008). https://pubmed.ncbi.nlm.nih.gov/18285556/ DOI: 10.2337/db07-1552
Complete structured claim and evidence
Berberine increased lactate release in HepG2 and C2C12 cells, including during AMPK-pathway blockade.
Berberine → Cellular lactate release source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/25072399.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a", "start_char": 0, "end_char": 1385, "text_sha256": "aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a"}
experimental_model
Pharmacological inhibition, siRNA and dominant-negative AMPK experiments
exposure
Berberine concentration-response; 20 micromolar in phosphorylation experiments
limitations
AMPK is not necessary for every glucose response. This does not show that all other berberine actions are AMPK-independent; cell concentrations may exceed circulating parent drug.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human HepG2 hepatocytes and mouse C2C12 myotubes
plain_language
More glycolytic use of glucose can increase lactate production; this is not a clinical lactic-acidosis incidence estimate.
primary_references
[berberine-p25072399] Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. (2014). https://pubmed.ncbi.nlm.nih.gov/25072399/ DOI: 10.1371/journal.pone.0103702
tissue_or_cell_type
Glucose consumption, lactate release and mitochondrial respiration
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 363–374
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pharmacological inhibition, siRNA and dominant-negative AMPK experiments · source_derived_draft · unverified_draft
### berberine-glycolytic-lactate Berberine increased lactate release in HepG2 and C2C12 cells, including during AMPK-pathway blockade. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: More glycolytic use of glucose can increase lactate production; this is not a clinical lactic-acidosis incidence estimate. organism: Human HepG2 hepatocytes and mouse C2C12 myotubes tissue_or_cell_type: Glucose consumption, lactate release and mitochondrial respiration experimental_model: Pharmacological inhibition, siRNA and dominant-negative AMPK experiments limitations: AMPK is not necessary for every glucose response. This does not show that all other berberine actions are AMPK-independent; cell concentrations may exceed circulating parent drug. exposure: Berberine concentration-response; 20 micromolar in phosphorylation experiments evidence_span: {"source_cache": "artifacts/berberine-research/25072399.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a", "start_char": 0, "end_char": 1385, "text_sha256": "aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a"} [berberine-p25072399] Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. (2014). https://pubmed.ncbi.nlm.nih.gov/25072399/ DOI: 10.1371/journal.pone.0103702
Complete structured claim and evidence
Berberine activated lysosome-associated AMPK in an AXIN1-dependent, PEN2-independent manner in HCT-116 cells.
Berberine → Lysosome-associated AMPK activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/37144221.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d", "start_char": 0, "end_char": 1212, "text_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d"}
experimental_model
Lysosome isolation, genetic perturbation and coimmunoprecipitation
exposure
Low-dose berberine experiments; AXIN1 loss, PEN2 perturbation and UHRF1 overexpression
limitations
Cancer-cell signaling model; low laboratory concentration is not proof of a mechanism at every human tissue exposure. Different dose/context from respiratory inhibition studies.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human HCT-116 cells
plain_language
A lysosomal signaling route adds detail beyond a single mitochondrial explanation.
primary_references
[berberine-p37144221] Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1. (2023). https://pubmed.ncbi.nlm.nih.gov/37144221/ DOI: 10.3389/fphar.2023.1148611
tissue_or_cell_type
Lysosomal AMPK and UHRF1 regulation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 376–387
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lysosome isolation, genetic perturbation and coimmunoprecipitation · source_derived_draft · unverified_draft
### berberine-lysosomal-ampk Berberine activated lysosome-associated AMPK in an AXIN1-dependent, PEN2-independent manner in HCT-116 cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A lysosomal signaling route adds detail beyond a single mitochondrial explanation. organism: Human HCT-116 cells tissue_or_cell_type: Lysosomal AMPK and UHRF1 regulation experimental_model: Lysosome isolation, genetic perturbation and coimmunoprecipitation limitations: Cancer-cell signaling model; low laboratory concentration is not proof of a mechanism at every human tissue exposure. Different dose/context from respiratory inhibition studies. exposure: Low-dose berberine experiments; AXIN1 loss, PEN2 perturbation and UHRF1 overexpression evidence_span: {"source_cache": "artifacts/berberine-research/37144221.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d", "start_char": 0, "end_char": 1212, "text_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d"} [berberine-p37144221] Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1. (2023). https://pubmed.ncbi.nlm.nih.gov/37144221/ DOI: 10.3389/fphar.2023.1148611
Complete structured claim and evidence
Berberine promoted UHRF1 degradation and reduced its expression.
Berberine → Human UHRF1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/37144221.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d", "start_char": 0, "end_char": 1212, "text_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d"}
experimental_model
Lysosome isolation, genetic perturbation and coimmunoprecipitation
exposure
Low-dose berberine experiments; AXIN1 loss, PEN2 perturbation and UHRF1 overexpression
limitations
Cancer-cell signaling model; low laboratory concentration is not proof of a mechanism at every human tissue exposure. Different dose/context from respiratory inhibition studies.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human HCT-116 cells
plain_language
Removing a signaling regulator can help sustain AMPK activity.
primary_references
[berberine-p37144221] Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1. (2023). https://pubmed.ncbi.nlm.nih.gov/37144221/ DOI: 10.3389/fphar.2023.1148611
tissue_or_cell_type
Lysosomal AMPK and UHRF1 regulation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 389–400
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lysosome isolation, genetic perturbation and coimmunoprecipitation · source_derived_draft · unverified_draft
### berberine-uhrf1-degradation Berberine promoted UHRF1 degradation and reduced its expression. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing a signaling regulator can help sustain AMPK activity. organism: Human HCT-116 cells tissue_or_cell_type: Lysosomal AMPK and UHRF1 regulation experimental_model: Lysosome isolation, genetic perturbation and coimmunoprecipitation limitations: Cancer-cell signaling model; low laboratory concentration is not proof of a mechanism at every human tissue exposure. Different dose/context from respiratory inhibition studies. exposure: Low-dose berberine experiments; AXIN1 loss, PEN2 perturbation and UHRF1 overexpression evidence_span: {"source_cache": "artifacts/berberine-research/37144221.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d", "start_char": 0, "end_char": 1212, "text_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d"} [berberine-p37144221] Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1. (2023). https://pubmed.ncbi.nlm.nih.gov/37144221/ DOI: 10.3389/fphar.2023.1148611
Complete structured claim and evidence
Berberine reduced association between UHRF1 and AMPK alpha 1.
Berberine → UHRF1 association with AMPK alpha 1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/37144221.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d", "start_char": 0, "end_char": 1212, "text_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d"}
experimental_model
Lysosome isolation, genetic perturbation and coimmunoprecipitation
exposure
Low-dose berberine experiments; AXIN1 loss, PEN2 perturbation and UHRF1 overexpression
limitations
Cancer-cell signaling model; low laboratory concentration is not proof of a mechanism at every human tissue exposure. Different dose/context from respiratory inhibition studies.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human HCT-116 cells
plain_language
The interaction between two separately stored proteins changed.
primary_references
[berberine-p37144221] Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1. (2023). https://pubmed.ncbi.nlm.nih.gov/37144221/ DOI: 10.3389/fphar.2023.1148611
tissue_or_cell_type
Lysosomal AMPK and UHRF1 regulation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 402–413
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lysosome isolation, genetic perturbation and coimmunoprecipitation · source_derived_draft · unverified_draft
### berberine-uhrf1-association Berberine reduced association between UHRF1 and AMPK alpha 1. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The interaction between two separately stored proteins changed. organism: Human HCT-116 cells tissue_or_cell_type: Lysosomal AMPK and UHRF1 regulation experimental_model: Lysosome isolation, genetic perturbation and coimmunoprecipitation limitations: Cancer-cell signaling model; low laboratory concentration is not proof of a mechanism at every human tissue exposure. Different dose/context from respiratory inhibition studies. exposure: Low-dose berberine experiments; AXIN1 loss, PEN2 perturbation and UHRF1 overexpression evidence_span: {"source_cache": "artifacts/berberine-research/37144221.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d", "start_char": 0, "end_char": 1212, "text_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d"} [berberine-p37144221] Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1. (2023). https://pubmed.ncbi.nlm.nih.gov/37144221/ DOI: 10.3389/fphar.2023.1148611
Complete structured claim and evidence
AXIN1 loss impaired the berberine response of lysosomal AMPK.
Human AXIN1 → Lysosome-associated AMPK activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/berberine-research/37144221.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d", "start_char": 0, "end_char": 1212, "text_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d"}
experimental_model
Lysosome isolation, genetic perturbation and coimmunoprecipitation
exposure
Low-dose berberine experiments; AXIN1 loss, PEN2 perturbation and UHRF1 overexpression
limitations
Cancer-cell signaling model; low laboratory concentration is not proof of a mechanism at every human tissue exposure. Different dose/context from respiratory inhibition studies.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human HCT-116 cells
plain_language
This branch cannot operate normally without its scaffold.
primary_references
[berberine-p37144221] Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1. (2023). https://pubmed.ncbi.nlm.nih.gov/37144221/ DOI: 10.3389/fphar.2023.1148611
tissue_or_cell_type
Lysosomal AMPK and UHRF1 regulation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 415–426
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lysosome isolation, genetic perturbation and coimmunoprecipitation · source_derived_draft · unverified_draft
### berberine-axin1-loss AXIN1 loss impaired the berberine response of lysosomal AMPK. Condition category: machinery_impairment nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This branch cannot operate normally without its scaffold. organism: Human HCT-116 cells tissue_or_cell_type: Lysosomal AMPK and UHRF1 regulation experimental_model: Lysosome isolation, genetic perturbation and coimmunoprecipitation limitations: Cancer-cell signaling model; low laboratory concentration is not proof of a mechanism at every human tissue exposure. Different dose/context from respiratory inhibition studies. exposure: Low-dose berberine experiments; AXIN1 loss, PEN2 perturbation and UHRF1 overexpression evidence_span: {"source_cache": "artifacts/berberine-research/37144221.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d", "start_char": 0, "end_char": 1212, "text_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d"} [berberine-p37144221] Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1. (2023). https://pubmed.ncbi.nlm.nih.gov/37144221/ DOI: 10.3389/fphar.2023.1148611
Complete structured claim and evidence
UHRF1 overexpression abolished berberine-induced AMPK activation in the tested cells.
Human UHRF1 → AMP-activated protein kinase complexes source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/37144221.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d", "start_char": 0, "end_char": 1212, "text_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d"}
experimental_model
Lysosome isolation, genetic perturbation and coimmunoprecipitation
exposure
Low-dose berberine experiments; AXIN1 loss, PEN2 perturbation and UHRF1 overexpression
limitations
Cancer-cell signaling model; low laboratory concentration is not proof of a mechanism at every human tissue exposure. Different dose/context from respiratory inhibition studies.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human HCT-116 cells
plain_language
Increasing the negative regulator prevented the observed response.
primary_references
[berberine-p37144221] Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1. (2023). https://pubmed.ncbi.nlm.nih.gov/37144221/ DOI: 10.3389/fphar.2023.1148611
tissue_or_cell_type
Lysosomal AMPK and UHRF1 regulation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 428–439
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lysosome isolation, genetic perturbation and coimmunoprecipitation · source_derived_draft · unverified_draft
### berberine-uhrf1-overexpression UHRF1 overexpression abolished berberine-induced AMPK activation in the tested cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Increasing the negative regulator prevented the observed response. organism: Human HCT-116 cells tissue_or_cell_type: Lysosomal AMPK and UHRF1 regulation experimental_model: Lysosome isolation, genetic perturbation and coimmunoprecipitation limitations: Cancer-cell signaling model; low laboratory concentration is not proof of a mechanism at every human tissue exposure. Different dose/context from respiratory inhibition studies. exposure: Low-dose berberine experiments; AXIN1 loss, PEN2 perturbation and UHRF1 overexpression evidence_span: {"source_cache": "artifacts/berberine-research/37144221.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d", "start_char": 0, "end_char": 1212, "text_sha256": "e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d"} [berberine-p37144221] Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1. (2023). https://pubmed.ncbi.nlm.nih.gov/37144221/ DOI: 10.3389/fphar.2023.1148611
Complete structured claim and evidence
Berberine stabilized LDLR mRNA through a regulatory region in its proximal 3-prime untranslated region.
Berberine → LDLR mRNA stability source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/15531889.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac2a9817f85e5c1f4f520590f1f2cb1ca820cce75b79120852f616f7ce5bea2f", "start_char": 0, "end_char": 1032, "text_sha256": "ac2a9817f85e5c1f4f520590f1f2cb1ca820cce75b79120852f616f7ce5bea2f"}
experimental_model
Human hepatoma mRNA stability/promoter experiments, animal and small clinical arms
exposure
Berberine exposure with ERK-dependence assays
limitations
Clinical lipid outcomes do not directly prove this molecular route caused the human effect. Cell response was reported independent of SREBP.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human hepatoma cells for molecular claims
plain_language
The cell retained the receptor-building message for longer.
primary_references
[berberine-p15531889] Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. (2004). https://pubmed.ncbi.nlm.nih.gov/15531889/ DOI: 10.1038/nm1135
tissue_or_cell_type
LDLR post-transcriptional regulation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 441–452
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human hepatoma mRNA stability/promoter experiments, animal and small clinical arms · source_derived_draft · unverified_draft
### berberine-ldlr-stability Berberine stabilized LDLR mRNA through a regulatory region in its proximal 3-prime untranslated region. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell retained the receptor-building message for longer. organism: Human hepatoma cells for molecular claims tissue_or_cell_type: LDLR post-transcriptional regulation experimental_model: Human hepatoma mRNA stability/promoter experiments, animal and small clinical arms limitations: Clinical lipid outcomes do not directly prove this molecular route caused the human effect. Cell response was reported independent of SREBP. exposure: Berberine exposure with ERK-dependence assays evidence_span: {"source_cache": "artifacts/berberine-research/15531889.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac2a9817f85e5c1f4f520590f1f2cb1ca820cce75b79120852f616f7ce5bea2f", "start_char": 0, "end_char": 1032, "text_sha256": "ac2a9817f85e5c1f4f520590f1f2cb1ca820cce75b79120852f616f7ce5bea2f"} [berberine-p15531889] Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. (2004). https://pubmed.ncbi.nlm.nih.gov/15531889/ DOI: 10.1038/nm1135
Complete structured claim and evidence
Berberine accelerated ubiquitin-associated proteasomal degradation of HNF1A protein in HepG2 cells.
Berberine → Human hepatocyte nuclear factor 1 alpha / HNF1A supersededungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/25540198.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446", "start_char": 0, "end_char": 1769, "text_sha256": "08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446"}
experimental_model
Protein-turnover and proteasome-inhibitor experiments
exposure
Berberine, ubiquitin assays and proteasome inhibition
limitations
HNF1A protein turnover differs from HNF1A gene transcription. Proteasome inhibitors are experimental probes, not suggested combination treatment.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human HepG2 cells; separate mouse and hamster arms
plain_language
The cell made less of a cholesterol-regulating signal because its upstream regulator was degraded.
primary_references
[berberine-p25540198] Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1α protein expression through the ubiquitin-proteasome degradation pathway. (2015). https://pubmed.ncbi.nlm.nih.gov/25540198/ DOI: 10.1074/jbc.m114.597229
tissue_or_cell_type
HNF1A and PCSK9 gene regulation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 467–478
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein-turnover and proteasome-inhibitor experiments · source_derived_draft · unverified_draft
### berberine-hnf1a-degradation Berberine accelerated ubiquitin-associated proteasomal degradation of HNF1A protein in HepG2 cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell made less of a cholesterol-regulating signal because its upstream regulator was degraded. organism: Human HepG2 cells; separate mouse and hamster arms tissue_or_cell_type: HNF1A and PCSK9 gene regulation experimental_model: Protein-turnover and proteasome-inhibitor experiments limitations: HNF1A protein turnover differs from HNF1A gene transcription. Proteasome inhibitors are experimental probes, not suggested combination treatment. exposure: Berberine, ubiquitin assays and proteasome inhibition evidence_span: {"source_cache": "artifacts/berberine-research/25540198.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446", "start_char": 0, "end_char": 1769, "text_sha256": "08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446"} [berberine-p25540198] Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1α protein expression through the ubiquitin-proteasome degradation pathway. (2015). https://pubmed.ncbi.nlm.nih.gov/25540198/ DOI: 10.1074/jbc.m114.597229
Complete structured claim and evidence
Berberine lowered HNF1A-dependent PCSK9 transcription; proteasome inhibition prevented this response.
Berberine → PCSK9 transcription source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/25540198.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446", "start_char": 0, "end_char": 1769, "text_sha256": "08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446"}
experimental_model
Protein-turnover and proteasome-inhibitor experiments
exposure
Berberine, ubiquitin assays and proteasome inhibition
limitations
HNF1A protein turnover differs from HNF1A gene transcription. Proteasome inhibitors are experimental probes, not suggested combination treatment.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human HepG2 cells; separate mouse and hamster arms
plain_language
This route regulates a protein that controls LDL-receptor availability.
primary_references
[berberine-p25540198] Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1α protein expression through the ubiquitin-proteasome degradation pathway. (2015). https://pubmed.ncbi.nlm.nih.gov/25540198/ DOI: 10.1074/jbc.m114.597229
tissue_or_cell_type
HNF1A and PCSK9 gene regulation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 480–491
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein-turnover and proteasome-inhibitor experiments · source_derived_draft · unverified_draft
### berberine-pcsk9-transcription Berberine lowered HNF1A-dependent PCSK9 transcription; proteasome inhibition prevented this response. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This route regulates a protein that controls LDL-receptor availability. organism: Human HepG2 cells; separate mouse and hamster arms tissue_or_cell_type: HNF1A and PCSK9 gene regulation experimental_model: Protein-turnover and proteasome-inhibitor experiments limitations: HNF1A protein turnover differs from HNF1A gene transcription. Proteasome inhibitors are experimental probes, not suggested combination treatment. exposure: Berberine, ubiquitin assays and proteasome inhibition evidence_span: {"source_cache": "artifacts/berberine-research/25540198.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446", "start_char": 0, "end_char": 1769, "text_sha256": "08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446"} [berberine-p25540198] Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1α protein expression through the ubiquitin-proteasome degradation pathway. (2015). https://pubmed.ncbi.nlm.nih.gov/25540198/ DOI: 10.1074/jbc.m114.597229
Complete structured claim and evidence
Berberine increased INSR mRNA and protein in human liver cells through PKC-dependent promoter activation.
Berberine → Insulin receptor / INSR source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/19059538.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "70e22b36b13efcbb36d7f27b417fe72dc96ba2f384f01a8d037bfc2d3213ef23", "start_char": 0, "end_char": 1461, "text_sha256": "70e22b36b13efcbb36d7f27b417fe72dc96ba2f384f01a8d037bfc2d3213ef23"}
experimental_model
Promoter assays, gene silencing and insulin-dependence experiments
exposure
Berberine with or without insulin, INSR siRNA or PKC inhibition
limitations
This insulin-dependent route does not replace insulin in insulin-deficient disease. Other models show insulin-independent routes; those observations are not discarded.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human liver cells and separate rodent experiments
plain_language
The cells increased the machinery that receives an insulin signal.
primary_references
[berberine-p19059538] Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. (2009). https://pubmed.ncbi.nlm.nih.gov/19059538/ DOI: 10.1016/j.metabol.2008.08.013
tissue_or_cell_type
Insulin receptor expression and glucose consumption
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 493–504
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter assays, gene silencing and insulin-dependence experiments · source_derived_draft · unverified_draft
### berberine-insr-expression Berberine increased INSR mRNA and protein in human liver cells through PKC-dependent promoter activation. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cells increased the machinery that receives an insulin signal. organism: Human liver cells and separate rodent experiments tissue_or_cell_type: Insulin receptor expression and glucose consumption experimental_model: Promoter assays, gene silencing and insulin-dependence experiments limitations: This insulin-dependent route does not replace insulin in insulin-deficient disease. Other models show insulin-independent routes; those observations are not discarded. exposure: Berberine with or without insulin, INSR siRNA or PKC inhibition evidence_span: {"source_cache": "artifacts/berberine-research/19059538.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "70e22b36b13efcbb36d7f27b417fe72dc96ba2f384f01a8d037bfc2d3213ef23", "start_char": 0, "end_char": 1461, "text_sha256": "70e22b36b13efcbb36d7f27b417fe72dc96ba2f384f01a8d037bfc2d3213ef23"} [berberine-p19059538] Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. (2009). https://pubmed.ncbi.nlm.nih.gov/19059538/ DOI: 10.1016/j.metabol.2008.08.013
Complete structured claim and evidence
INSR silencing diminished the insulin-dependent increase in glucose consumption associated with berberine-enhanced receptor expression.
Insulin receptor / INSR → Cellular glucose consumption source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/berberine-research/19059538.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "70e22b36b13efcbb36d7f27b417fe72dc96ba2f384f01a8d037bfc2d3213ef23", "start_char": 0, "end_char": 1461, "text_sha256": "70e22b36b13efcbb36d7f27b417fe72dc96ba2f384f01a8d037bfc2d3213ef23"}
experimental_model
Promoter assays, gene silencing and insulin-dependence experiments
exposure
Berberine with or without insulin, INSR siRNA or PKC inhibition
limitations
This insulin-dependent route does not replace insulin in insulin-deficient disease. Other models show insulin-independent routes; those observations are not discarded.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human liver cells and separate rodent experiments
plain_language
A sensitizing signal cannot substitute for missing receptor machinery.
primary_references
[berberine-p19059538] Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. (2009). https://pubmed.ncbi.nlm.nih.gov/19059538/ DOI: 10.1016/j.metabol.2008.08.013
tissue_or_cell_type
Insulin receptor expression and glucose consumption
trigger_kind
machinery_impairment Imported condition classification; unverified.
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 506–517
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter assays, gene silencing and insulin-dependence experiments · source_derived_draft · unverified_draft
### berberine-insr-loss INSR silencing diminished the insulin-dependent increase in glucose consumption associated with berberine-enhanced receptor expression. Condition category: machinery_impairment nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sensitizing signal cannot substitute for missing receptor machinery. organism: Human liver cells and separate rodent experiments tissue_or_cell_type: Insulin receptor expression and glucose consumption experimental_model: Promoter assays, gene silencing and insulin-dependence experiments limitations: This insulin-dependent route does not replace insulin in insulin-deficient disease. Other models show insulin-independent routes; those observations are not discarded. exposure: Berberine with or without insulin, INSR siRNA or PKC inhibition evidence_span: {"source_cache": "artifacts/berberine-research/19059538.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "70e22b36b13efcbb36d7f27b417fe72dc96ba2f384f01a8d037bfc2d3213ef23", "start_char": 0, "end_char": 1461, "text_sha256": "70e22b36b13efcbb36d7f27b417fe72dc96ba2f384f01a8d037bfc2d3213ef23"} [berberine-p19059538] Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. (2009). https://pubmed.ncbi.nlm.nih.gov/19059538/ DOI: 10.1016/j.metabol.2008.08.013
Complete structured claim and evidence
Berberine acutely increased GLUT1-mediated uptake in L929 cells and decreased apparent glucose-uptake Km without changing Vmax.
Berberine → Mouse glucose transporter GLUT1 / Slc2a1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/21545824.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "18e315a501ae688fc71a7761667e58ae71fdd4b3fae19b7ef0f83889dbae2825", "start_char": 0, "end_char": 1865, "text_sha256": "18e315a501ae688fc71a7761667e58ae71fdd4b3fae19b7ef0f83889dbae2825"}
experimental_model
Acute glucose-uptake kinetics and kinase inhibitors
exposure
Minutes of berberine exposure; maximum stimulation above 40 micromolar
limitations
Single-cell model and high concentrations; kinase inhibitors are not fully selective. No inference of a matching human glucose-lowering magnitude.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Mouse L929 fibroblasts expressing GLUT1
plain_language
A transporter can move glucose differently without the cell making more transporters.
primary_references
[berberine-p21545824] Berberine acutely activates the glucose transport activity of GLUT1. (2011). https://pubmed.ncbi.nlm.nih.gov/21545824/ DOI: 10.1016/j.biochi.2011.04.013
tissue_or_cell_type
GLUT1-mediated glucose uptake
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 519–530
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute glucose-uptake kinetics and kinase inhibitors · source_derived_draft · unverified_draft
### berberine-glut1-activation Berberine acutely increased GLUT1-mediated uptake in L929 cells and decreased apparent glucose-uptake Km without changing Vmax. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter can move glucose differently without the cell making more transporters. organism: Mouse L929 fibroblasts expressing GLUT1 tissue_or_cell_type: GLUT1-mediated glucose uptake experimental_model: Acute glucose-uptake kinetics and kinase inhibitors limitations: Single-cell model and high concentrations; kinase inhibitors are not fully selective. No inference of a matching human glucose-lowering magnitude. exposure: Minutes of berberine exposure; maximum stimulation above 40 micromolar evidence_span: {"source_cache": "artifacts/berberine-research/21545824.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "18e315a501ae688fc71a7761667e58ae71fdd4b3fae19b7ef0f83889dbae2825", "start_char": 0, "end_char": 1865, "text_sha256": "18e315a501ae688fc71a7761667e58ae71fdd4b3fae19b7ef0f83889dbae2825"} [berberine-p21545824] Berberine acutely activates the glucose transport activity of GLUT1. (2011). https://pubmed.ncbi.nlm.nih.gov/21545824/ DOI: 10.1016/j.biochi.2011.04.013
Complete structured claim and evidence
Berberine increased Nrf2 reporter activity in Caco-2 cells.
Berberine → Human Nrf2 / NFE2L2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/29891588.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405", "start_char": 0, "end_char": 1752, "text_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405"}
experimental_model
Nrf2 reporter, gene silencing and expression assays
exposure
Berberine concentration and time response
limitations
Transporter expression after prolonged exposure is not the same endpoint as acute competitive inhibition. Rat colitis improvement does not establish human IBD efficacy.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human Caco-2 cells; rat colitis in a separate arm
plain_language
An exposure can turn on a transcriptional response linked to an efflux pump.
primary_references
[berberine-p29891588] Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms. (2018). https://pubmed.ncbi.nlm.nih.gov/29891588/ DOI: 10.1124/jpet.118.249615
tissue_or_cell_type
Nrf2-dependent ABCB1 expression
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 532–543
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nrf2 reporter, gene silencing and expression assays · source_derived_draft · unverified_draft
### berberine-nrf2-reporter Berberine increased Nrf2 reporter activity in Caco-2 cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An exposure can turn on a transcriptional response linked to an efflux pump. organism: Human Caco-2 cells; rat colitis in a separate arm tissue_or_cell_type: Nrf2-dependent ABCB1 expression experimental_model: Nrf2 reporter, gene silencing and expression assays limitations: Transporter expression after prolonged exposure is not the same endpoint as acute competitive inhibition. Rat colitis improvement does not establish human IBD efficacy. exposure: Berberine concentration and time response evidence_span: {"source_cache": "artifacts/berberine-research/29891588.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405", "start_char": 0, "end_char": 1752, "text_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405"} [berberine-p29891588] Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms. (2018). https://pubmed.ncbi.nlm.nih.gov/29891588/ DOI: 10.1124/jpet.118.249615
Complete structured claim and evidence
Berberine increased MDR1/ABCB1 expression; Nrf2 silencing abolished the gene response in Caco-2 cells.
Berberine → Human P-glycoprotein / ABCB1 / MDR1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/29891588.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405", "start_char": 0, "end_char": 1752, "text_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405"}
experimental_model
Nrf2 reporter, gene silencing and expression assays
exposure
Berberine concentration and time response
limitations
Transporter expression after prolonged exposure is not the same endpoint as acute competitive inhibition. Rat colitis improvement does not establish human IBD efficacy.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human Caco-2 cells; rat colitis in a separate arm
plain_language
Repeated exposure can increase the pump that exports drugs.
primary_references
[berberine-p29891588] Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms. (2018). https://pubmed.ncbi.nlm.nih.gov/29891588/ DOI: 10.1124/jpet.118.249615
tissue_or_cell_type
Nrf2-dependent ABCB1 expression
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 545–556
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nrf2 reporter, gene silencing and expression assays · source_derived_draft · unverified_draft
### berberine-abcb1-expression Berberine increased MDR1/ABCB1 expression; Nrf2 silencing abolished the gene response in Caco-2 cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Repeated exposure can increase the pump that exports drugs. organism: Human Caco-2 cells; rat colitis in a separate arm tissue_or_cell_type: Nrf2-dependent ABCB1 expression experimental_model: Nrf2 reporter, gene silencing and expression assays limitations: Transporter expression after prolonged exposure is not the same endpoint as acute competitive inhibition. Rat colitis improvement does not establish human IBD efficacy. exposure: Berberine concentration and time response evidence_span: {"source_cache": "artifacts/berberine-research/29891588.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405", "start_char": 0, "end_char": 1752, "text_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405"} [berberine-p29891588] Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms. (2018). https://pubmed.ncbi.nlm.nih.gov/29891588/ DOI: 10.1124/jpet.118.249615
Complete structured claim and evidence
Berberine inhibited a cAMP-dependent, chromanol-sensitive basolateral potassium current consistent with KCNQ1 by 88%.
Berberine → Basolateral KCNQ1-associated potassium current source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"}
experimental_model
Ussing-chamber short-circuit current, patch clamp and kinase perturbation
exposure
Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar
limitations
Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human T84 colonic cells
plain_language
Reducing potassium recycling can limit chloride secretion across intestinal cells.
primary_references
[berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033
tissue_or_cell_type
Basolateral potassium recycling and chloride secretion
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 558–569
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ussing-chamber short-circuit current, patch clamp and kinase perturbation · source_derived_draft · unverified_draft
### berberine-kcnq1-current Berberine inhibited a cAMP-dependent, chromanol-sensitive basolateral potassium current consistent with KCNQ1 by 88%. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing potassium recycling can limit chloride secretion across intestinal cells. organism: Human T84 colonic cells tissue_or_cell_type: Basolateral potassium recycling and chloride secretion experimental_model: Ussing-chamber short-circuit current, patch clamp and kinase perturbation limitations: Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1. exposure: Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar evidence_span: {"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"} [berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033
Complete structured claim and evidence
Berberine did not affect apical chloride conductance in the permeabilized-cell experiments.
Berberine → Chloride ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"}
experimental_model
Ussing-chamber short-circuit current, patch clamp and kinase perturbation
exposure
Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar
limitations
Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human T84 colonic cells
plain_language
Lower total chloride secretion did not require directly blocking the apical chloride conductance.
primary_references
[berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033
tissue_or_cell_type
Basolateral potassium recycling and chloride secretion
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 584–595
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ussing-chamber short-circuit current, patch clamp and kinase perturbation · source_derived_draft · unverified_draft
### berberine-apical-chloride-null Berberine did not affect apical chloride conductance in the permeabilized-cell experiments. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lower total chloride secretion did not require directly blocking the apical chloride conductance. organism: Human T84 colonic cells tissue_or_cell_type: Basolateral potassium recycling and chloride secretion experimental_model: Ussing-chamber short-circuit current, patch clamp and kinase perturbation limitations: Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1. exposure: Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar evidence_span: {"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"} [berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033
Complete structured claim and evidence
Berberine did not affect basolateral sodium-potassium ATPase activity in this model.
Berberine → Sodium-potassium ATPase complexes source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"}
experimental_model
Ussing-chamber short-circuit current, patch clamp and kinase perturbation
exposure
Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar
limitations
Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human T84 colonic cells
plain_language
The pump and the potassium channel were tested separately.
primary_references
[berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033
tissue_or_cell_type
Basolateral potassium recycling and chloride secretion
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 597–608
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ussing-chamber short-circuit current, patch clamp and kinase perturbation · source_derived_draft · unverified_draft
### berberine-sodium-pump-null Berberine did not affect basolateral sodium-potassium ATPase activity in this model. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pump and the potassium channel were tested separately. organism: Human T84 colonic cells tissue_or_cell_type: Basolateral potassium recycling and chloride secretion experimental_model: Ussing-chamber short-circuit current, patch clamp and kinase perturbation limitations: Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1. exposure: Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar evidence_span: {"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"} [berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033
Complete structured claim and evidence
Berberine blocked hERG current, with IC50 about 3.1 micromolar in HEK293 cells and 80 micromolar in oocytes.
Berberine → hERG / KCNH2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/16424781.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "45057bbc2da5981b23041d50a91a8e0adacfc150adf66d23daac0402f8ead682", "start_char": 0, "end_char": 1322, "text_sha256": "45057bbc2da5981b23041d50a91a8e0adacfc150adf66d23daac0402f8ead682"}
experimental_model
Patch clamp and site-directed mutagenesis
exposure
Berberine concentration-response; hERG mutations
limitations
Different expression systems had markedly different IC50 values. Channel inhibition is a hazard mechanism, not an incidence estimate for arrhythmia in supplement users.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human hERG expressed in HEK293 cells and Xenopus oocytes
plain_language
A potassium channel needed for cardiac repolarization is a separate safety-related target.
primary_references
[berberine-p16424781] Block of HERG channels by berberine: mechanisms of voltage- and state-dependence probed with site-directed mutant channels. (2006). https://pubmed.ncbi.nlm.nih.gov/16424781/ DOI: 10.1097/01.fjc.0000191564.52242.00
tissue_or_cell_type
Cardiac potassium-channel model
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 610–621
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patch clamp and site-directed mutagenesis · source_derived_draft · unverified_draft
### berberine-herg-block Berberine blocked hERG current, with IC50 about 3.1 micromolar in HEK293 cells and 80 micromolar in oocytes. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A potassium channel needed for cardiac repolarization is a separate safety-related target. organism: Human hERG expressed in HEK293 cells and Xenopus oocytes tissue_or_cell_type: Cardiac potassium-channel model experimental_model: Patch clamp and site-directed mutagenesis limitations: Different expression systems had markedly different IC50 values. Channel inhibition is a hazard mechanism, not an incidence estimate for arrhythmia in supplement users. exposure: Berberine concentration-response; hERG mutations evidence_span: {"source_cache": "artifacts/berberine-research/16424781.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "45057bbc2da5981b23041d50a91a8e0adacfc150adf66d23daac0402f8ead682", "start_char": 0, "end_char": 1322, "text_sha256": "45057bbc2da5981b23041d50a91a8e0adacfc150adf66d23daac0402f8ead682"} [berberine-p16424781] Block of HERG channels by berberine: mechanisms of voltage- and state-dependence probed with site-directed mutant channels. (2006). https://pubmed.ncbi.nlm.nih.gov/16424781/ DOI: 10.1097/01.fjc.0000191564.52242.00
Complete structured claim and evidence
Berberine reduced hERG cell-surface abundance through mechanisms involving caveolin-1 and hERG S6 residues.
Berberine → Cell-surface hERG abundance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/26543354.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "56eb3a544eb8700c50931e8bbeb16a24786259d3fb9feebb0b2cbe9e81f02734", "start_char": 0, "end_char": 1453, "text_sha256": "56eb3a544eb8700c50931e8bbeb16a24786259d3fb9feebb0b2cbe9e81f02734"}
experimental_model
Cell-surface protein regulation and mutagenesis
exposure
Berberine exposure and caveolin-1 knockdown
limitations
Channel abundance and direct current block are distinct mechanisms. Experimental rescue compounds are not clinical antidote recommendations.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human hERG-expressing HEK293 cells
plain_language
Longer exposure can reduce the number of channels as well as block their current.
primary_references
[berberine-p26543354] Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/26543354/ DOI: 10.2147/dddt.s91561
tissue_or_cell_type
hERG membrane stability
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 623–634
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-surface protein regulation and mutagenesis · source_derived_draft · unverified_draft
### berberine-herg-abundance Berberine reduced hERG cell-surface abundance through mechanisms involving caveolin-1 and hERG S6 residues. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Longer exposure can reduce the number of channels as well as block their current. organism: Human hERG-expressing HEK293 cells tissue_or_cell_type: hERG membrane stability experimental_model: Cell-surface protein regulation and mutagenesis limitations: Channel abundance and direct current block are distinct mechanisms. Experimental rescue compounds are not clinical antidote recommendations. exposure: Berberine exposure and caveolin-1 knockdown evidence_span: {"source_cache": "artifacts/berberine-research/26543354.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "56eb3a544eb8700c50931e8bbeb16a24786259d3fb9feebb0b2cbe9e81f02734", "start_char": 0, "end_char": 1453, "text_sha256": "56eb3a544eb8700c50931e8bbeb16a24786259d3fb9feebb0b2cbe9e81f02734"} [berberine-p26543354] Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/26543354/ DOI: 10.2147/dddt.s91561
Complete structured claim and evidence
Berberine approximately doubled the losartan/E-3174 ratio, indicating reduced CYP2C9 activity.
Berberine → CYP2C9 activity measured by probe-drug phenotyping source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"}
experimental_model
Two-phase randomized crossover enzyme-phenotyping study
exposure
Berberine 300 mg three times daily for 14 days versus placebo
limitations
Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Healthy human male volunteers; 17 completed
plain_language
The drug-to-active-metabolite ratio changed in people.
primary_references
[berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2
tissue_or_cell_type
Oral probe pharmacokinetics and urinary metabolite ratios
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 649–660
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-phase randomized crossover enzyme-phenotyping study · source_derived_draft · unverified_draft
### berberine-human-cyp-2c9 Berberine approximately doubled the losartan/E-3174 ratio, indicating reduced CYP2C9 activity. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The drug-to-active-metabolite ratio changed in people. organism: Healthy human male volunteers; 17 completed tissue_or_cell_type: Oral probe pharmacokinetics and urinary metabolite ratios experimental_model: Two-phase randomized crossover enzyme-phenotyping study limitations: Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence. exposure: Berberine 300 mg three times daily for 14 days versus placebo evidence_span: {"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"} [berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2
Complete structured claim and evidence
No statistically significant change in caffeine probe pharmacokinetics was found after berberine.
Berberine → CYP1A2 activity measured by probe-drug phenotyping source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"}
experimental_model
Two-phase randomized crossover enzyme-phenotyping study
exposure
Berberine 300 mg three times daily for 14 days versus placebo
limitations
Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Healthy human male volunteers; 17 completed
plain_language
This study did not show a CYP1A2 effect matching the effects on three other enzymes.
primary_references
[berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2
tissue_or_cell_type
Oral probe pharmacokinetics and urinary metabolite ratios
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 675–686
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-phase randomized crossover enzyme-phenotyping study · source_derived_draft · unverified_draft
### berberine-human-cyp-1a2-null No statistically significant change in caffeine probe pharmacokinetics was found after berberine. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This study did not show a CYP1A2 effect matching the effects on three other enzymes. organism: Healthy human male volunteers; 17 completed tissue_or_cell_type: Oral probe pharmacokinetics and urinary metabolite ratios experimental_model: Two-phase randomized crossover enzyme-phenotyping study limitations: Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence. exposure: Berberine 300 mg three times daily for 14 days versus placebo evidence_span: {"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"} [berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2
Complete structured claim and evidence
No statistically significant change in omeprazole probe pharmacokinetics was found after berberine.
Berberine → CYP2C19 activity measured by probe-drug phenotyping source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"}
experimental_model
Two-phase randomized crossover enzyme-phenotyping study
exposure
Berberine 300 mg three times daily for 14 days versus placebo
limitations
Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Healthy human male volunteers; 17 completed
plain_language
The CYP2C19 probe result was also negative under these conditions.
primary_references
[berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2
tissue_or_cell_type
Oral probe pharmacokinetics and urinary metabolite ratios
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 688–699
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-phase randomized crossover enzyme-phenotyping study · source_derived_draft · unverified_draft
### berberine-human-cyp-2c19-null No statistically significant change in omeprazole probe pharmacokinetics was found after berberine. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The CYP2C19 probe result was also negative under these conditions. organism: Healthy human male volunteers; 17 completed tissue_or_cell_type: Oral probe pharmacokinetics and urinary metabolite ratios experimental_model: Two-phase randomized crossover enzyme-phenotyping study limitations: Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence. exposure: Berberine 300 mg three times daily for 14 days versus placebo evidence_span: {"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"} [berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2
Complete structured claim and evidence
Midazolam AUC to infinity increased approximately 40% and Cmax 38% after repeated berberine.
Berberine → Plasma midazolam exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"}
experimental_model
Two-phase randomized crossover enzyme-phenotyping study
exposure
Berberine 300 mg three times daily for 14 days versus placebo
limitations
Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Healthy human male volunteers; 17 completed
plain_language
One actual medicine had greater systemic exposure in this controlled study.
primary_references
[berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2
tissue_or_cell_type
Oral probe pharmacokinetics and urinary metabolite ratios
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 701–712
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-phase randomized crossover enzyme-phenotyping study · source_derived_draft · unverified_draft
### berberine-midazolam-auc Midazolam AUC to infinity increased approximately 40% and Cmax 38% after repeated berberine. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: One actual medicine had greater systemic exposure in this controlled study. organism: Healthy human male volunteers; 17 completed tissue_or_cell_type: Oral probe pharmacokinetics and urinary metabolite ratios experimental_model: Two-phase randomized crossover enzyme-phenotyping study limitations: Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence. exposure: Berberine 300 mg three times daily for 14 days versus placebo evidence_span: {"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"} [berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2
Complete structured claim and evidence
In six transplant recipients, cyclosporine AUC rose 34.5% after 12 days of berberine.
Berberine → Cyclosporine A / ciclosporin A source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/16133554.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a86b1b0f9ad77889da596b013f9f229556d53d825dac1b8bb2ba6ed094a68ad", "start_char": 0, "end_char": 2232, "text_sha256": "7a86b1b0f9ad77889da596b013f9f229556d53d825dac1b8bb2ba6ed094a68ad"}
experimental_model
Randomized controlled transplant study with separate six-person pharmacokinetic arm
exposure
52 recipients per clinical arm; berberine 0.2 g three times daily for three months; six-person 12-day PK comparison
limitations
Observed interaction is clinically relevant, but the proposed CYP3A4 explanation was not uniquely established. Baseline change and between-group difference must not be confused.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Renal-transplant recipients
plain_language
A pharmacokinetic subset confirmed increased exposure; it is not an instruction to lower the prescribed dose.
primary_references
[berberine-p16133554] Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. (2005). https://pubmed.ncbi.nlm.nih.gov/16133554/ DOI: 10.1007/s00228-005-0952-3
tissue_or_cell_type
Cyclosporine blood concentrations
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 727–738
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled transplant study with separate six-person pharmacokinetic arm · source_derived_draft · unverified_draft
### berberine-cyclosporine-pk In six transplant recipients, cyclosporine AUC rose 34.5% after 12 days of berberine. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A pharmacokinetic subset confirmed increased exposure; it is not an instruction to lower the prescribed dose. organism: Renal-transplant recipients tissue_or_cell_type: Cyclosporine blood concentrations experimental_model: Randomized controlled transplant study with separate six-person pharmacokinetic arm limitations: Observed interaction is clinically relevant, but the proposed CYP3A4 explanation was not uniquely established. Baseline change and between-group difference must not be confused. exposure: 52 recipients per clinical arm; berberine 0.2 g three times daily for three months; six-person 12-day PK comparison evidence_span: {"source_cache": "artifacts/berberine-research/16133554.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a86b1b0f9ad77889da596b013f9f229556d53d825dac1b8bb2ba6ed094a68ad", "start_char": 0, "end_char": 2232, "text_sha256": "7a86b1b0f9ad77889da596b013f9f229556d53d825dac1b8bb2ba6ed094a68ad"} [berberine-p16133554] Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. (2005). https://pubmed.ncbi.nlm.nih.gov/16133554/ DOI: 10.1007/s00228-005-0952-3
Complete structured claim and evidence
The 3 mg/kg cyclosporine arm showed a 19.2% AUC increase with berberine.
Berberine → Blood cyclosporine exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/16541194.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e1c8258a18a8214a1124f3624eff9cb67151c5f54393ff2e3e7322b3bdf53b5", "start_char": 0, "end_char": 1615, "text_sha256": "1e1c8258a18a8214a1124f3624eff9cb67151c5f54393ff2e3e7322b3bdf53b5"}
experimental_model
Two small healthy-volunteer pharmacokinetic experiments
exposure
3 mg/kg cyclosporine with a single 0.3 g berberine dose; separate 6 mg/kg cyclosporine after 10 days of berberine
limitations
Different cyclosporine doses and berberine schedules limit direct comparison. A null arm does not negate the positive arm or transplant finding.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Two groups of six healthy male volunteers
plain_language
Interaction size depended on the tested regimen.
primary_references
[berberine-p16541194] The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers. (2006). https://pubmed.ncbi.nlm.nih.gov/16541194/ DOI: 10.1358/mf.2006.28.1.962774
tissue_or_cell_type
Cyclosporine pharmacokinetics
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 740–751
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two small healthy-volunteer pharmacokinetic experiments · source_derived_draft · unverified_draft
### berberine-cyclosporine-low-dose The 3 mg/kg cyclosporine arm showed a 19.2% AUC increase with berberine. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Interaction size depended on the tested regimen. organism: Two groups of six healthy male volunteers tissue_or_cell_type: Cyclosporine pharmacokinetics experimental_model: Two small healthy-volunteer pharmacokinetic experiments limitations: Different cyclosporine doses and berberine schedules limit direct comparison. A null arm does not negate the positive arm or transplant finding. exposure: 3 mg/kg cyclosporine with a single 0.3 g berberine dose; separate 6 mg/kg cyclosporine after 10 days of berberine evidence_span: {"source_cache": "artifacts/berberine-research/16541194.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e1c8258a18a8214a1124f3624eff9cb67151c5f54393ff2e3e7322b3bdf53b5", "start_char": 0, "end_char": 1615, "text_sha256": "1e1c8258a18a8214a1124f3624eff9cb67151c5f54393ff2e3e7322b3bdf53b5"} [berberine-p16541194] The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers. (2006). https://pubmed.ncbi.nlm.nih.gov/16541194/ DOI: 10.1358/mf.2006.28.1.962774
Complete structured claim and evidence
The separate 6 mg/kg cyclosporine arm found no significant pharmacokinetic change after repeated berberine.
Berberine → Blood cyclosporine exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/16541194.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e1c8258a18a8214a1124f3624eff9cb67151c5f54393ff2e3e7322b3bdf53b5", "start_char": 0, "end_char": 1615, "text_sha256": "1e1c8258a18a8214a1124f3624eff9cb67151c5f54393ff2e3e7322b3bdf53b5"}
experimental_model
Two small healthy-volunteer pharmacokinetic experiments
exposure
3 mg/kg cyclosporine with a single 0.3 g berberine dose; separate 6 mg/kg cyclosporine after 10 days of berberine
limitations
Different cyclosporine doses and berberine schedules limit direct comparison. A null arm does not negate the positive arm or transplant finding.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Two groups of six healthy male volunteers
plain_language
Both outcomes remain visible with their distinct dosing conditions.
primary_references
[berberine-p16541194] The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers. (2006). https://pubmed.ncbi.nlm.nih.gov/16541194/ DOI: 10.1358/mf.2006.28.1.962774
tissue_or_cell_type
Cyclosporine pharmacokinetics
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 753–764
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two small healthy-volunteer pharmacokinetic experiments · source_derived_draft · unverified_draft
### berberine-cyclosporine-null-arm The separate 6 mg/kg cyclosporine arm found no significant pharmacokinetic change after repeated berberine. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both outcomes remain visible with their distinct dosing conditions. organism: Two groups of six healthy male volunteers tissue_or_cell_type: Cyclosporine pharmacokinetics experimental_model: Two small healthy-volunteer pharmacokinetic experiments limitations: Different cyclosporine doses and berberine schedules limit direct comparison. A null arm does not negate the positive arm or transplant finding. exposure: 3 mg/kg cyclosporine with a single 0.3 g berberine dose; separate 6 mg/kg cyclosporine after 10 days of berberine evidence_span: {"source_cache": "artifacts/berberine-research/16541194.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e1c8258a18a8214a1124f3624eff9cb67151c5f54393ff2e3e7322b3bdf53b5", "start_char": 0, "end_char": 1615, "text_sha256": "1e1c8258a18a8214a1124f3624eff9cb67151c5f54393ff2e3e7322b3bdf53b5"} [berberine-p16541194] The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers. (2006). https://pubmed.ncbi.nlm.nih.gov/16541194/ DOI: 10.1358/mf.2006.28.1.962774
Complete structured claim and evidence
Berberine inhibited rat OCT1-mediated metformin uptake in transfected cells, with reported IC50 7.28 micromolar.
Berberine → Rat organic cation transporter 1 / Oct1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/25359200.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db", "start_char": 0, "end_char": 1353, "text_sha256": "e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db"}
experimental_model
Transporter-expressing cells and intravenous rat pharmacokinetics
exposure
Intravenous metformin 2 mg/kg and berberine 10 mg/kg in rats; in-vitro concentration-response
limitations
HEK293 is the host cell, not proof that the expressed transporter is human; the indexed proteins are rat Slc22a1/Slc22a2. Intravenous rat results cannot determine an oral human interaction. Assayed substrate was metformin, not thiamine.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Rat OCT1/2 in HEK293 cells and rats; rat protein identity indexed in primary-publication chemical records
plain_language
Transport inhibition is a distinct interaction mechanism from liver CYP inhibition.
primary_references
[berberine-p25359200] Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin. (2015). https://pubmed.ncbi.nlm.nih.gov/25359200/ DOI: 10.1007/s12272-014-0510-6
tissue_or_cell_type
Metformin uptake and disposition
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 766–777
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-expressing cells and intravenous rat pharmacokinetics · source_derived_draft · unverified_draft
### berberine-metformin-rat-slc22a1 Berberine inhibited rat OCT1-mediated metformin uptake in transfected cells, with reported IC50 7.28 micromolar. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Transport inhibition is a distinct interaction mechanism from liver CYP inhibition. organism: Rat OCT1/2 in HEK293 cells and rats; rat protein identity indexed in primary-publication chemical records tissue_or_cell_type: Metformin uptake and disposition experimental_model: Transporter-expressing cells and intravenous rat pharmacokinetics limitations: HEK293 is the host cell, not proof that the expressed transporter is human; the indexed proteins are rat Slc22a1/Slc22a2. Intravenous rat results cannot determine an oral human interaction. Assayed substrate was metformin, not thiamine. exposure: Intravenous metformin 2 mg/kg and berberine 10 mg/kg in rats; in-vitro concentration-response evidence_span: {"source_cache": "artifacts/berberine-research/25359200.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db", "start_char": 0, "end_char": 1353, "text_sha256": "e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db"} [berberine-p25359200] Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin. (2015). https://pubmed.ncbi.nlm.nih.gov/25359200/ DOI: 10.1007/s12272-014-0510-6
Complete structured claim and evidence
Berberine inhibited rat OCT2-mediated metformin uptake in transfected cells, with reported IC50 11.3 micromolar.
Berberine → Rat organic cation transporter 2 / Oct2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/25359200.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db", "start_char": 0, "end_char": 1353, "text_sha256": "e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db"}
experimental_model
Transporter-expressing cells and intravenous rat pharmacokinetics
exposure
Intravenous metformin 2 mg/kg and berberine 10 mg/kg in rats; in-vitro concentration-response
limitations
HEK293 is the host cell, not proof that the expressed transporter is human; the indexed proteins are rat Slc22a1/Slc22a2. Intravenous rat results cannot determine an oral human interaction. Assayed substrate was metformin, not thiamine.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Rat OCT1/2 in HEK293 cells and rats; rat protein identity indexed in primary-publication chemical records
plain_language
Transport inhibition is a distinct interaction mechanism from liver CYP inhibition.
primary_references
[berberine-p25359200] Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin. (2015). https://pubmed.ncbi.nlm.nih.gov/25359200/ DOI: 10.1007/s12272-014-0510-6
tissue_or_cell_type
Metformin uptake and disposition
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 779–790
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-expressing cells and intravenous rat pharmacokinetics · source_derived_draft · unverified_draft
### berberine-metformin-rat-slc22a2 Berberine inhibited rat OCT2-mediated metformin uptake in transfected cells, with reported IC50 11.3 micromolar. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Transport inhibition is a distinct interaction mechanism from liver CYP inhibition. organism: Rat OCT1/2 in HEK293 cells and rats; rat protein identity indexed in primary-publication chemical records tissue_or_cell_type: Metformin uptake and disposition experimental_model: Transporter-expressing cells and intravenous rat pharmacokinetics limitations: HEK293 is the host cell, not proof that the expressed transporter is human; the indexed proteins are rat Slc22a1/Slc22a2. Intravenous rat results cannot determine an oral human interaction. Assayed substrate was metformin, not thiamine. exposure: Intravenous metformin 2 mg/kg and berberine 10 mg/kg in rats; in-vitro concentration-response evidence_span: {"source_cache": "artifacts/berberine-research/25359200.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db", "start_char": 0, "end_char": 1353, "text_sha256": "e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db"} [berberine-p25359200] Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin. (2015). https://pubmed.ncbi.nlm.nih.gov/25359200/ DOI: 10.1007/s12272-014-0510-6
Complete structured claim and evidence
Intravenous berberine coadministration increased metformin AUC and reduced systemic clearance in rats.
Berberine → Plasma metformin exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/25359200.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db", "start_char": 0, "end_char": 1353, "text_sha256": "e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db"}
experimental_model
Transporter-expressing cells and intravenous rat pharmacokinetics
exposure
Intravenous metformin 2 mg/kg and berberine 10 mg/kg in rats; in-vitro concentration-response
limitations
HEK293 is the host cell, not proof that the expressed transporter is human; the indexed proteins are rat Slc22a1/Slc22a2. Intravenous rat results cannot determine an oral human interaction. Assayed substrate was metformin, not thiamine.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Rat OCT1/2 in HEK293 cells and rats; rat protein identity indexed in primary-publication chemical records
plain_language
Blocking uptake or elimination can increase circulating drug after intravenous dosing.
primary_references
[berberine-p25359200] Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin. (2015). https://pubmed.ncbi.nlm.nih.gov/25359200/ DOI: 10.1007/s12272-014-0510-6
tissue_or_cell_type
Metformin uptake and disposition
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 792–803
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-expressing cells and intravenous rat pharmacokinetics · source_derived_draft · unverified_draft
### berberine-metformin-iv-rat Intravenous berberine coadministration increased metformin AUC and reduced systemic clearance in rats. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking uptake or elimination can increase circulating drug after intravenous dosing. organism: Rat OCT1/2 in HEK293 cells and rats; rat protein identity indexed in primary-publication chemical records tissue_or_cell_type: Metformin uptake and disposition experimental_model: Transporter-expressing cells and intravenous rat pharmacokinetics limitations: HEK293 is the host cell, not proof that the expressed transporter is human; the indexed proteins are rat Slc22a1/Slc22a2. Intravenous rat results cannot determine an oral human interaction. Assayed substrate was metformin, not thiamine. exposure: Intravenous metformin 2 mg/kg and berberine 10 mg/kg in rats; in-vitro concentration-response evidence_span: {"source_cache": "artifacts/berberine-research/25359200.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db", "start_char": 0, "end_char": 1353, "text_sha256": "e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db"} [berberine-p25359200] Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin. (2015). https://pubmed.ncbi.nlm.nih.gov/25359200/ DOI: 10.1007/s12272-014-0510-6
Complete structured claim and evidence
Berberine inhibited rat OCT1-mediated metformin transport, with IC50 18.8 micromolar.
Berberine → Rat organic cation transporter 1 / Oct1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/30428337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8", "start_char": 0, "end_char": 1775, "text_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8"}
experimental_model
Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells
exposure
Oral metformin/berberine coadministration; concentration-dependent transport assays
limitations
Route differs from the intravenous rat study. Changes in plasma, kidney tissue and excretion are separate outcomes; not proof of improved human combination efficacy.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Rats and recombinant rat OCT1, OCT2 and MATE1
plain_language
This identifies the rat transporter independently, preserving species.
primary_references
[berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010
tissue_or_cell_type
Intestinal uptake, kidney distribution and excretion
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 805–816
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells · source_derived_draft · unverified_draft
### berberine-rat-metformin-rat-slc22a1 Berberine inhibited rat OCT1-mediated metformin transport, with IC50 18.8 micromolar. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This identifies the rat transporter independently, preserving species. organism: Rats and recombinant rat OCT1, OCT2 and MATE1 tissue_or_cell_type: Intestinal uptake, kidney distribution and excretion experimental_model: Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells limitations: Route differs from the intravenous rat study. Changes in plasma, kidney tissue and excretion are separate outcomes; not proof of improved human combination efficacy. exposure: Oral metformin/berberine coadministration; concentration-dependent transport assays evidence_span: {"source_cache": "artifacts/berberine-research/30428337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8", "start_char": 0, "end_char": 1775, "text_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8"} [berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010
Complete structured claim and evidence
Berberine inhibited rat OCT2-mediated metformin transport, with IC50 1.02 micromolar.
Berberine → Rat organic cation transporter 2 / Oct2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/30428337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8", "start_char": 0, "end_char": 1775, "text_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8"}
experimental_model
Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells
exposure
Oral metformin/berberine coadministration; concentration-dependent transport assays
limitations
Route differs from the intravenous rat study. Changes in plasma, kidney tissue and excretion are separate outcomes; not proof of improved human combination efficacy.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Rats and recombinant rat OCT1, OCT2 and MATE1
plain_language
This identifies the rat transporter independently, preserving species.
primary_references
[berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010
tissue_or_cell_type
Intestinal uptake, kidney distribution and excretion
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 818–829
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells · source_derived_draft · unverified_draft
### berberine-rat-metformin-rat-slc22a2 Berberine inhibited rat OCT2-mediated metformin transport, with IC50 1.02 micromolar. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This identifies the rat transporter independently, preserving species. organism: Rats and recombinant rat OCT1, OCT2 and MATE1 tissue_or_cell_type: Intestinal uptake, kidney distribution and excretion experimental_model: Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells limitations: Route differs from the intravenous rat study. Changes in plasma, kidney tissue and excretion are separate outcomes; not proof of improved human combination efficacy. exposure: Oral metformin/berberine coadministration; concentration-dependent transport assays evidence_span: {"source_cache": "artifacts/berberine-research/30428337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8", "start_char": 0, "end_char": 1775, "text_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8"} [berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010
Complete structured claim and evidence
Berberine inhibited rat MATE1-mediated metformin transport, with IC50 10.7 micromolar.
Berberine → Rat multidrug and toxin extrusion protein 1 / Mate1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/30428337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8", "start_char": 0, "end_char": 1775, "text_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8"}
experimental_model
Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells
exposure
Oral metformin/berberine coadministration; concentration-dependent transport assays
limitations
Route differs from the intravenous rat study. Changes in plasma, kidney tissue and excretion are separate outcomes; not proof of improved human combination efficacy.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Rats and recombinant rat OCT1, OCT2 and MATE1
plain_language
This identifies the rat transporter independently, preserving species.
primary_references
[berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010
tissue_or_cell_type
Intestinal uptake, kidney distribution and excretion
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 831–842
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells · source_derived_draft · unverified_draft
### berberine-rat-metformin-rat-slc47a1 Berberine inhibited rat MATE1-mediated metformin transport, with IC50 10.7 micromolar. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This identifies the rat transporter independently, preserving species. organism: Rats and recombinant rat OCT1, OCT2 and MATE1 tissue_or_cell_type: Intestinal uptake, kidney distribution and excretion experimental_model: Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells limitations: Route differs from the intravenous rat study. Changes in plasma, kidney tissue and excretion are separate outcomes; not proof of improved human combination efficacy. exposure: Oral metformin/berberine coadministration; concentration-dependent transport assays evidence_span: {"source_cache": "artifacts/berberine-research/30428337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8", "start_char": 0, "end_char": 1775, "text_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8"} [berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010
Complete structured claim and evidence
Oral berberine coadministration decreased metformin Cmax and AUC over the first four hours in rats.
Berberine → Plasma metformin exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/30428337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8", "start_char": 0, "end_char": 1775, "text_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8"}
experimental_model
Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells
exposure
Oral metformin/berberine coadministration; concentration-dependent transport assays
limitations
Route differs from the intravenous rat study. Changes in plasma, kidney tissue and excretion are separate outcomes; not proof of improved human combination efficacy.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Rats and recombinant rat OCT1, OCT2 and MATE1
plain_language
An intestinal effect can reverse the direction seen after intravenous dosing.
primary_references
[berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010
tissue_or_cell_type
Intestinal uptake, kidney distribution and excretion
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 844–855
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells · source_derived_draft · unverified_draft
### berberine-metformin-oral-rat Oral berberine coadministration decreased metformin Cmax and AUC over the first four hours in rats. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An intestinal effect can reverse the direction seen after intravenous dosing. organism: Rats and recombinant rat OCT1, OCT2 and MATE1 tissue_or_cell_type: Intestinal uptake, kidney distribution and excretion experimental_model: Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells limitations: Route differs from the intravenous rat study. Changes in plasma, kidney tissue and excretion are separate outcomes; not proof of improved human combination efficacy. exposure: Oral metformin/berberine coadministration; concentration-dependent transport assays evidence_span: {"source_cache": "artifacts/berberine-research/30428337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8", "start_char": 0, "end_char": 1775, "text_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8"} [berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010
Complete structured claim and evidence
Berberine increased kidney metformin concentration despite lower early plasma exposure in the oral rat study.
Berberine → Kidney metformin concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/30428337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8", "start_char": 0, "end_char": 1775, "text_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8"}
experimental_model
Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells
exposure
Oral metformin/berberine coadministration; concentration-dependent transport assays
limitations
Route differs from the intravenous rat study. Changes in plasma, kidney tissue and excretion are separate outcomes; not proof of improved human combination efficacy.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Rats and recombinant rat OCT1, OCT2 and MATE1
plain_language
Lower blood levels do not necessarily mean lower levels in every organ.
primary_references
[berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010
tissue_or_cell_type
Intestinal uptake, kidney distribution and excretion
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 857–868
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells · source_derived_draft · unverified_draft
### berberine-metformin-kidney-rat Berberine increased kidney metformin concentration despite lower early plasma exposure in the oral rat study. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lower blood levels do not necessarily mean lower levels in every organ. organism: Rats and recombinant rat OCT1, OCT2 and MATE1 tissue_or_cell_type: Intestinal uptake, kidney distribution and excretion experimental_model: Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells limitations: Route differs from the intravenous rat study. Changes in plasma, kidney tissue and excretion are separate outcomes; not proof of improved human combination efficacy. exposure: Oral metformin/berberine coadministration; concentration-dependent transport assays evidence_span: {"source_cache": "artifacts/berberine-research/30428337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8", "start_char": 0, "end_char": 1775, "text_sha256": "d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8"} [berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010
Complete structured claim and evidence
Goldenseal reduced metformin AUC by 23% without changing its half-life or renal clearance.
Goldenseal extract, composition specified by study → Plasma metformin exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/33174626.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0dbd2401295c8f6e093461899378d5e9b7c2c5757be0bd12d335edf07216afa9", "start_char": 0, "end_char": 1812, "text_sha256": "0dbd2401295c8f6e093461899378d5e9b7c2c5757be0bd12d335edf07216afa9"}
experimental_model
Clinical transporter-probe cocktail with in-vitro prediction
exposure
Characterized goldenseal botanical product, not purified berberine
limitations
Goldenseal contains multiple alkaloids. This result must not be attributed exclusively to berberine; unchanged renal clearance favors an absorption-related explanation.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Sixteen healthy human volunteers
plain_language
The tested botanical mixture changed metformin exposure; purified berberine was not the clinical intervention.
primary_references
[berberine-p33174626] Assessing Transporter-Mediated Natural Product-Drug Interactions Via In vitro-In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail. (2021). https://pubmed.ncbi.nlm.nih.gov/33174626/ DOI: 10.1002/cpt.2107
tissue_or_cell_type
Oral metformin exposure
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 870–881
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical transporter-probe cocktail with in-vitro prediction · source_derived_draft · unverified_draft
### berberine-goldenseal-metformin Goldenseal reduced metformin AUC by 23% without changing its half-life or renal clearance. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested botanical mixture changed metformin exposure; purified berberine was not the clinical intervention. organism: Sixteen healthy human volunteers tissue_or_cell_type: Oral metformin exposure experimental_model: Clinical transporter-probe cocktail with in-vitro prediction limitations: Goldenseal contains multiple alkaloids. This result must not be attributed exclusively to berberine; unchanged renal clearance favors an absorption-related explanation. exposure: Characterized goldenseal botanical product, not purified berberine evidence_span: {"source_cache": "artifacts/berberine-research/33174626.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0dbd2401295c8f6e093461899378d5e9b7c2c5757be0bd12d335edf07216afa9", "start_char": 0, "end_char": 1812, "text_sha256": "0dbd2401295c8f6e093461899378d5e9b7c2c5757be0bd12d335edf07216afa9"} [berberine-p33174626] Assessing Transporter-Mediated Natural Product-Drug Interactions Via In vitro-In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail. (2021). https://pubmed.ncbi.nlm.nih.gov/33174626/ DOI: 10.1002/cpt.2107
Complete structured claim and evidence
Goldenseal extract inhibited OCT3-mediated metformin transport in transfected cells.
Goldenseal extract, composition specified by study → Human organic cation transporter 3 / OCT3 / SLC22A3 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/37562957.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646", "start_char": 0, "end_char": 2598, "text_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646"}
experimental_model
Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics
exposure
Goldenseal extract and isolated berberine or hydrastine were tested separately
limitations
Extract potency was normalized to berberine content but does not mean berberine alone caused the effect. Transported probe was metformin, so thiamine depletion was not measured.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human transporters in HEK293 cells; mice
plain_language
The mixture and each transporter remain separate database entries.
primary_references
[berberine-p37562957] Goldenseal-Mediated Inhibition of Intestinal Uptake Transporters Decreases Metformin Systemic Exposure in Mice. (2023). https://pubmed.ncbi.nlm.nih.gov/37562957/ DOI: 10.1124/dmd.123.001360
tissue_or_cell_type
Intestinal uptake
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 883–894
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics · source_derived_draft · unverified_draft
### berberine-goldenseal-slc22a3 Goldenseal extract inhibited OCT3-mediated metformin transport in transfected cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mixture and each transporter remain separate database entries. organism: Human transporters in HEK293 cells; mice tissue_or_cell_type: Intestinal uptake experimental_model: Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics limitations: Extract potency was normalized to berberine content but does not mean berberine alone caused the effect. Transported probe was metformin, so thiamine depletion was not measured. exposure: Goldenseal extract and isolated berberine or hydrastine were tested separately evidence_span: {"source_cache": "artifacts/berberine-research/37562957.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646", "start_char": 0, "end_char": 2598, "text_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646"} [berberine-p37562957] Goldenseal-Mediated Inhibition of Intestinal Uptake Transporters Decreases Metformin Systemic Exposure in Mice. (2023). https://pubmed.ncbi.nlm.nih.gov/37562957/ DOI: 10.1124/dmd.123.001360
Complete structured claim and evidence
Goldenseal extract inhibited PMAT-mediated metformin transport in transfected cells.
Goldenseal extract, composition specified by study → Human plasma membrane monoamine transporter / PMAT / SLC29A4 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/37562957.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646", "start_char": 0, "end_char": 2598, "text_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646"}
experimental_model
Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics
exposure
Goldenseal extract and isolated berberine or hydrastine were tested separately
limitations
Extract potency was normalized to berberine content but does not mean berberine alone caused the effect. Transported probe was metformin, so thiamine depletion was not measured.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human transporters in HEK293 cells; mice
plain_language
The mixture and each transporter remain separate database entries.
primary_references
[berberine-p37562957] Goldenseal-Mediated Inhibition of Intestinal Uptake Transporters Decreases Metformin Systemic Exposure in Mice. (2023). https://pubmed.ncbi.nlm.nih.gov/37562957/ DOI: 10.1124/dmd.123.001360
tissue_or_cell_type
Intestinal uptake
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 896–907
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics · source_derived_draft · unverified_draft
### berberine-goldenseal-slc29a4 Goldenseal extract inhibited PMAT-mediated metformin transport in transfected cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mixture and each transporter remain separate database entries. organism: Human transporters in HEK293 cells; mice tissue_or_cell_type: Intestinal uptake experimental_model: Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics limitations: Extract potency was normalized to berberine content but does not mean berberine alone caused the effect. Transported probe was metformin, so thiamine depletion was not measured. exposure: Goldenseal extract and isolated berberine or hydrastine were tested separately evidence_span: {"source_cache": "artifacts/berberine-research/37562957.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646", "start_char": 0, "end_char": 2598, "text_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646"} [berberine-p37562957] Goldenseal-Mediated Inhibition of Intestinal Uptake Transporters Decreases Metformin Systemic Exposure in Mice. (2023). https://pubmed.ncbi.nlm.nih.gov/37562957/ DOI: 10.1124/dmd.123.001360
Complete structured claim and evidence
Goldenseal extract inhibited THTR2-mediated metformin transport in transfected cells.
Goldenseal extract, composition specified by study → Human thiamine transporter 2 / SLC19A3 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/37562957.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646", "start_char": 0, "end_char": 2598, "text_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646"}
experimental_model
Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics
exposure
Goldenseal extract and isolated berberine or hydrastine were tested separately
limitations
Extract potency was normalized to berberine content but does not mean berberine alone caused the effect. Transported probe was metformin, so thiamine depletion was not measured.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human transporters in HEK293 cells; mice
plain_language
The mixture and each transporter remain separate database entries.
primary_references
[berberine-p37562957] Goldenseal-Mediated Inhibition of Intestinal Uptake Transporters Decreases Metformin Systemic Exposure in Mice. (2023). https://pubmed.ncbi.nlm.nih.gov/37562957/ DOI: 10.1124/dmd.123.001360
tissue_or_cell_type
Intestinal uptake
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 909–920
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics · source_derived_draft · unverified_draft
### berberine-goldenseal-slc19a3 Goldenseal extract inhibited THTR2-mediated metformin transport in transfected cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mixture and each transporter remain separate database entries. organism: Human transporters in HEK293 cells; mice tissue_or_cell_type: Intestinal uptake experimental_model: Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics limitations: Extract potency was normalized to berberine content but does not mean berberine alone caused the effect. Transported probe was metformin, so thiamine depletion was not measured. exposure: Goldenseal extract and isolated berberine or hydrastine were tested separately evidence_span: {"source_cache": "artifacts/berberine-research/37562957.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646", "start_char": 0, "end_char": 2598, "text_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646"} [berberine-p37562957] Goldenseal-Mediated Inhibition of Intestinal Uptake Transporters Decreases Metformin Systemic Exposure in Mice. (2023). https://pubmed.ncbi.nlm.nih.gov/37562957/ DOI: 10.1124/dmd.123.001360
Complete structured claim and evidence
Isolated berberine did not alter metformin pharmacokinetics in the mouse experiment, whereas goldenseal extract reduced metformin Cmax.
Berberine → Plasma metformin exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/37562957.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646", "start_char": 0, "end_char": 2598, "text_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646"}
experimental_model
Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics
exposure
Goldenseal extract and isolated berberine or hydrastine were tested separately
limitations
Extract potency was normalized to berberine content but does not mean berberine alone caused the effect. Transported probe was metformin, so thiamine depletion was not measured.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human transporters in HEK293 cells; mice
plain_language
The whole botanical product cannot be treated as equivalent to one ingredient.
primary_references
[berberine-p37562957] Goldenseal-Mediated Inhibition of Intestinal Uptake Transporters Decreases Metformin Systemic Exposure in Mice. (2023). https://pubmed.ncbi.nlm.nih.gov/37562957/ DOI: 10.1124/dmd.123.001360
tissue_or_cell_type
Intestinal uptake
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 922–933
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics · source_derived_draft · unverified_draft
### berberine-isolated-berberine-mouse-null Isolated berberine did not alter metformin pharmacokinetics in the mouse experiment, whereas goldenseal extract reduced metformin Cmax. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The whole botanical product cannot be treated as equivalent to one ingredient. organism: Human transporters in HEK293 cells; mice tissue_or_cell_type: Intestinal uptake experimental_model: Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics limitations: Extract potency was normalized to berberine content but does not mean berberine alone caused the effect. Transported probe was metformin, so thiamine depletion was not measured. exposure: Goldenseal extract and isolated berberine or hydrastine were tested separately evidence_span: {"source_cache": "artifacts/berberine-research/37562957.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646", "start_char": 0, "end_char": 2598, "text_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646"} [berberine-p37562957] Goldenseal-Mediated Inhibition of Intestinal Uptake Transporters Decreases Metformin Systemic Exposure in Mice. (2023). https://pubmed.ncbi.nlm.nih.gov/37562957/ DOI: 10.1124/dmd.123.001360
Complete structured claim and evidence
No clinically obvious pharmacokinetic interaction with simvastatin was detected in the tested berberine-chloride combination regimen.
Berberine → Plasma simvastatin exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/30587933.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f82b466cc2942fd70940935e1fa42174f135036017a589bc7fa86388e6f9e4be", "start_char": 0, "end_char": 2118, "text_sha256": "f82b466cc2942fd70940935e1fa42174f135036017a589bc7fa86388e6f9e4be"}
experimental_model
Open-label randomized parallel pharmacokinetic study
exposure
Single-dose and seven-day repeated treatment; berberine chloride alone or combined
limitations
Short, small healthy-volunteer study. Absence of an obvious interaction here does not establish unrestricted long-term safety in patients.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Sixty healthy Chinese participants across five groups
plain_language
The measured result limits a blanket claim that every relevant drug concentration must rise.
primary_references
[berberine-p30587933] Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: an open-label, randomized, parallel study in healthy Chinese subjects. (2019). https://pubmed.ncbi.nlm.nih.gov/30587933/ DOI: 10.2147/dddt.s185487
tissue_or_cell_type
Simvastatin and fenofibrate exposure
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 935–946
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Open-label randomized parallel pharmacokinetic study · source_derived_draft · unverified_draft
### berberine-clinical-statin-null No clinically obvious pharmacokinetic interaction with simvastatin was detected in the tested berberine-chloride combination regimen. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured result limits a blanket claim that every relevant drug concentration must rise. organism: Sixty healthy Chinese participants across five groups tissue_or_cell_type: Simvastatin and fenofibrate exposure experimental_model: Open-label randomized parallel pharmacokinetic study limitations: Short, small healthy-volunteer study. Absence of an obvious interaction here does not establish unrestricted long-term safety in patients. exposure: Single-dose and seven-day repeated treatment; berberine chloride alone or combined evidence_span: {"source_cache": "artifacts/berberine-research/30587933.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f82b466cc2942fd70940935e1fa42174f135036017a589bc7fa86388e6f9e4be", "start_char": 0, "end_char": 2118, "text_sha256": "f82b466cc2942fd70940935e1fa42174f135036017a589bc7fa86388e6f9e4be"} [berberine-p30587933] Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: an open-label, randomized, parallel study in healthy Chinese subjects. (2019). https://pubmed.ncbi.nlm.nih.gov/30587933/ DOI: 10.2147/dddt.s185487
Complete structured claim and evidence
No clinically obvious pharmacokinetic interaction with fenofibrate was detected in the tested berberine-chloride combination regimen.
Berberine → Plasma fenofibrate exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/30587933.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f82b466cc2942fd70940935e1fa42174f135036017a589bc7fa86388e6f9e4be", "start_char": 0, "end_char": 2118, "text_sha256": "f82b466cc2942fd70940935e1fa42174f135036017a589bc7fa86388e6f9e4be"}
experimental_model
Open-label randomized parallel pharmacokinetic study
exposure
Single-dose and seven-day repeated treatment; berberine chloride alone or combined
limitations
Short, small healthy-volunteer study. Absence of an obvious interaction here does not establish unrestricted long-term safety in patients.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Sixty healthy Chinese participants across five groups
plain_language
The measured result limits a blanket claim that every relevant drug concentration must rise.
primary_references
[berberine-p30587933] Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: an open-label, randomized, parallel study in healthy Chinese subjects. (2019). https://pubmed.ncbi.nlm.nih.gov/30587933/ DOI: 10.2147/dddt.s185487
tissue_or_cell_type
Simvastatin and fenofibrate exposure
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 948–959
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Open-label randomized parallel pharmacokinetic study · source_derived_draft · unverified_draft
### berberine-clinical-fibrate-null No clinically obvious pharmacokinetic interaction with fenofibrate was detected in the tested berberine-chloride combination regimen. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured result limits a blanket claim that every relevant drug concentration must rise. organism: Sixty healthy Chinese participants across five groups tissue_or_cell_type: Simvastatin and fenofibrate exposure experimental_model: Open-label randomized parallel pharmacokinetic study limitations: Short, small healthy-volunteer study. Absence of an obvious interaction here does not establish unrestricted long-term safety in patients. exposure: Single-dose and seven-day repeated treatment; berberine chloride alone or combined evidence_span: {"source_cache": "artifacts/berberine-research/30587933.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f82b466cc2942fd70940935e1fa42174f135036017a589bc7fa86388e6f9e4be", "start_char": 0, "end_char": 2118, "text_sha256": "f82b466cc2942fd70940935e1fa42174f135036017a589bc7fa86388e6f9e4be"} [berberine-p30587933] Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: an open-label, randomized, parallel study in healthy Chinese subjects. (2019). https://pubmed.ncbi.nlm.nih.gov/30587933/ DOI: 10.2147/dddt.s185487
Complete structured claim and evidence
Berberine displaced bilirubin from protein binding in vitro.
Berberine → Bilirubin binding to albumin source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
Bilirubin-binding assay and adult-rat exposure
exposure
Binding displacement assay; intraperitoneal berberine for one week in rats
limitations
No infant risk incidence was measured. Adult-rat parenteral exposure is not equivalent to oral adult supplementation; protein displacement is a biologically relevant concern for neonatal jaundice.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
In-vitro protein binding and adult rats
plain_language
Competition for a blood binding protein can change the unbound fraction.
primary_references
[berberine-p8513024] Displacement of bilirubin from albumin by berberine. (1993). https://pubmed.ncbi.nlm.nih.gov/8513024/ DOI: 10.1159/000243932
tissue_or_cell_type
Albumin-bound versus unbound bilirubin
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 961–972
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bilirubin-binding assay and adult-rat exposure · source_derived_draft · unverified_draft
### berberine-bilirubin-displacement Berberine displaced bilirubin from protein binding in vitro. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Competition for a blood binding protein can change the unbound fraction. organism: In-vitro protein binding and adult rats tissue_or_cell_type: Albumin-bound versus unbound bilirubin experimental_model: Bilirubin-binding assay and adult-rat exposure limitations: No infant risk incidence was measured. Adult-rat parenteral exposure is not equivalent to oral adult supplementation; protein displacement is a biologically relevant concern for neonatal jaundice. exposure: Binding displacement assay; intraperitoneal berberine for one week in rats evidence_span: {"source_cache": "artifacts/berberine-research/8513024.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ff3832e3aad7806081c5b3bd378eabf1595da6dd2a1f3bef664bb69c9d11334", "start_char": 0, "end_char": 1066, "text_sha256": "6ff3832e3aad7806081c5b3bd378eabf1595da6dd2a1f3bef664bb69c9d11334"} [berberine-p8513024] Displacement of bilirubin from albumin by berberine. (1993). https://pubmed.ncbi.nlm.nih.gov/8513024/ DOI: 10.1159/000243932
Complete structured claim and evidence
Repeated intraperitoneal berberine increased unbound bilirubin concentrations in adult rats.
Berberine → Unbound bilirubin concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/8513024.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ff3832e3aad7806081c5b3bd378eabf1595da6dd2a1f3bef664bb69c9d11334", "start_char": 0, "end_char": 1066, "text_sha256": "6ff3832e3aad7806081c5b3bd378eabf1595da6dd2a1f3bef664bb69c9d11334"}
experimental_model
Bilirubin-binding assay and adult-rat exposure
exposure
Binding displacement assay; intraperitoneal berberine for one week in rats
limitations
No infant risk incidence was measured. Adult-rat parenteral exposure is not equivalent to oral adult supplementation; protein displacement is a biologically relevant concern for neonatal jaundice.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
In-vitro protein binding and adult rats
plain_language
The laboratory binding concern also appeared in an animal exposure model.
primary_references
[berberine-p8513024] Displacement of bilirubin from albumin by berberine. (1993). https://pubmed.ncbi.nlm.nih.gov/8513024/ DOI: 10.1159/000243932
tissue_or_cell_type
Albumin-bound versus unbound bilirubin
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 974–985
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bilirubin-binding assay and adult-rat exposure · source_derived_draft · unverified_draft
### berberine-bilirubin-unbound-rat Repeated intraperitoneal berberine increased unbound bilirubin concentrations in adult rats. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The laboratory binding concern also appeared in an animal exposure model. organism: In-vitro protein binding and adult rats tissue_or_cell_type: Albumin-bound versus unbound bilirubin experimental_model: Bilirubin-binding assay and adult-rat exposure limitations: No infant risk incidence was measured. Adult-rat parenteral exposure is not equivalent to oral adult supplementation; protein displacement is a biologically relevant concern for neonatal jaundice. exposure: Binding displacement assay; intraperitoneal berberine for one week in rats evidence_span: {"source_cache": "artifacts/berberine-research/8513024.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ff3832e3aad7806081c5b3bd378eabf1595da6dd2a1f3bef664bb69c9d11334", "start_char": 0, "end_char": 1066, "text_sha256": "6ff3832e3aad7806081c5b3bd378eabf1595da6dd2a1f3bef664bb69c9d11334"} [berberine-p8513024] Displacement of bilirubin from albumin by berberine. (1993). https://pubmed.ncbi.nlm.nih.gov/8513024/ DOI: 10.1159/000243932
Complete structured claim and evidence
Oral berberine increased microbial butyrate production in the animal and bacterial-culture experiments.
Berberine → Gut microbial butyrate production source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"}
experimental_model
Bacterial culture and animal route/antibiotic experiments
exposure
Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison
limitations
Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents
plain_language
Microbes can turn a drug exposure into a change in metabolite supply.
primary_references
[berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
tissue_or_cell_type
Short-chain fatty acid production
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 987–998
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial culture and animal route/antibiotic experiments · source_derived_draft · unverified_draft
### berberine-butyrate-production Oral berberine increased microbial butyrate production in the animal and bacterial-culture experiments. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Microbes can turn a drug exposure into a change in metabolite supply. organism: Gut bacteria and rodents tissue_or_cell_type: Short-chain fatty acid production experimental_model: Bacterial culture and animal route/antibiotic experiments limitations: Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people. exposure: Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison evidence_span: {"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"} [berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
Complete structured claim and evidence
Berberine reduced bacterial ATP production in the tested gut bacterial systems.
Berberine → Gut bacterial ATP production source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"}
experimental_model
Bacterial culture and animal route/antibiotic experiments
exposure
Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison
limitations
Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents
plain_language
The bacterial energy state changed; this is not a measured human vitamin deficiency.
primary_references
[berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
tissue_or_cell_type
Short-chain fatty acid production
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1000–1011
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial culture and animal route/antibiotic experiments · source_derived_draft · unverified_draft
### berberine-bacterial-atp Berberine reduced bacterial ATP production in the tested gut bacterial systems. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The bacterial energy state changed; this is not a measured human vitamin deficiency. organism: Gut bacteria and rodents tissue_or_cell_type: Short-chain fatty acid production experimental_model: Bacterial culture and animal route/antibiotic experiments limitations: Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people. exposure: Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison evidence_span: {"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"} [berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
Complete structured claim and evidence
Berberine reduced bacterial NADH levels in the tested systems.
Berberine → Gut bacterial NADH content source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"}
experimental_model
Bacterial culture and animal route/antibiotic experiments
exposure
Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison
limitations
Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents
plain_language
The bacterial energy state changed; this is not a measured human vitamin deficiency.
primary_references
[berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
tissue_or_cell_type
Short-chain fatty acid production
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1013–1024
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial culture and animal route/antibiotic experiments · source_derived_draft · unverified_draft
### berberine-bacterial-nadh Berberine reduced bacterial NADH levels in the tested systems. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The bacterial energy state changed; this is not a measured human vitamin deficiency. organism: Gut bacteria and rodents tissue_or_cell_type: Short-chain fatty acid production experimental_model: Bacterial culture and animal route/antibiotic experiments limitations: Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people. exposure: Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison evidence_span: {"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"} [berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
Complete structured claim and evidence
The study reported increased bacterial phosphotransbutyrylase in the pathway associated with increased butyrate production.
Berberine → Bacterial phosphotransbutyrylases source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"}
experimental_model
Bacterial culture and animal route/antibiotic experiments
exposure
Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison
limitations
Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents
plain_language
Each bacterial enzyme family is recorded independently; species and isoform remain unresolved.
primary_references
[berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
tissue_or_cell_type
Short-chain fatty acid production
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1026–1037
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial culture and animal route/antibiotic experiments · source_derived_draft · unverified_draft
### berberine-butyrate-ptb The study reported increased bacterial phosphotransbutyrylase in the pathway associated with increased butyrate production. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Each bacterial enzyme family is recorded independently; species and isoform remain unresolved. organism: Gut bacteria and rodents tissue_or_cell_type: Short-chain fatty acid production experimental_model: Bacterial culture and animal route/antibiotic experiments limitations: Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people. exposure: Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison evidence_span: {"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"} [berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
Complete structured claim and evidence
The study reported increased bacterial butyrate kinase in the pathway associated with increased butyrate production.
Berberine → Bacterial butyrate kinases source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"}
experimental_model
Bacterial culture and animal route/antibiotic experiments
exposure
Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison
limitations
Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents
plain_language
Each bacterial enzyme family is recorded independently; species and isoform remain unresolved.
primary_references
[berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
tissue_or_cell_type
Short-chain fatty acid production
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1039–1050
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial culture and animal route/antibiotic experiments · source_derived_draft · unverified_draft
### berberine-butyrate-buk The study reported increased bacterial butyrate kinase in the pathway associated with increased butyrate production. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Each bacterial enzyme family is recorded independently; species and isoform remain unresolved. organism: Gut bacteria and rodents tissue_or_cell_type: Short-chain fatty acid production experimental_model: Bacterial culture and animal route/antibiotic experiments limitations: Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people. exposure: Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison evidence_span: {"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"} [berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
Complete structured claim and evidence
The study reported increased bacterial butyryl-CoA:acetate-CoA transferase in the pathway associated with increased butyrate production.
Berberine → Bacterial butyryl-CoA:acetate-CoA transferases source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"}
experimental_model
Bacterial culture and animal route/antibiotic experiments
exposure
Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison
limitations
Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents
plain_language
Each bacterial enzyme family is recorded independently; species and isoform remain unresolved.
primary_references
[berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
tissue_or_cell_type
Short-chain fatty acid production
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1052–1063
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial culture and animal route/antibiotic experiments · source_derived_draft · unverified_draft
### berberine-butyrate-bct The study reported increased bacterial butyryl-CoA:acetate-CoA transferase in the pathway associated with increased butyrate production. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Each bacterial enzyme family is recorded independently; species and isoform remain unresolved. organism: Gut bacteria and rodents tissue_or_cell_type: Short-chain fatty acid production experimental_model: Bacterial culture and animal route/antibiotic experiments limitations: Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people. exposure: Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison evidence_span: {"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"} [berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
Complete structured claim and evidence
Antibiotic pretreatment abolished the berberine-associated rise in butyrate.
Gut bacterial biomass → Gut microbial butyrate production source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"}
experimental_model
Bacterial culture and animal route/antibiotic experiments
exposure
Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison
limitations
Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents
plain_language
This branch weakened when the organisms producing the metabolite were removed.
primary_references
[berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
tissue_or_cell_type
Short-chain fatty acid production
trigger_kind
machinery_impairment Imported condition classification; unverified.
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1065–1076
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial culture and animal route/antibiotic experiments · source_derived_draft · unverified_draft
### berberine-butyrate-antibiotics Antibiotic pretreatment abolished the berberine-associated rise in butyrate. Condition category: machinery_impairment nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This branch weakened when the organisms producing the metabolite were removed. organism: Gut bacteria and rodents tissue_or_cell_type: Short-chain fatty acid production experimental_model: Bacterial culture and animal route/antibiotic experiments limitations: Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people. exposure: Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison evidence_span: {"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"} [berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
Complete structured claim and evidence
Berberine lowered TMA/TMAO production in choline-fed mice; labeled-choline tracing supported altered microbial conversion.
Berberine → Circulating trimethylamine N-oxide concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
Choline tracer, microbial culture, microbiome transfer and atherosclerosis models
exposure
Choline-supplemented chow and berberine; deuterated choline tracing
limitations
Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia
plain_language
A microbial change was linked to a circulating metabolite in animals.
primary_references
[berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
tissue_or_cell_type
Microbial choline metabolism
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1091–1102
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Choline tracer, microbial culture, microbiome transfer and atherosclerosis models · source_derived_draft · unverified_draft
### berberine-tmao-mice Berberine lowered TMA/TMAO production in choline-fed mice; labeled-choline tracing supported altered microbial conversion. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A microbial change was linked to a circulating metabolite in animals. organism: C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia tissue_or_cell_type: Microbial choline metabolism experimental_model: Choline tracer, microbial culture, microbiome transfer and atherosclerosis models limitations: Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake. exposure: Choline-supplemented chow and berberine; deuterated choline tracing evidence_span: {"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"} [berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
Complete structured claim and evidence
Metagenomics identified altered cutC/cntA abundance alongside changes in microbial composition after berberine.
Berberine → Gut microbial cutC and cntA gene abundance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"}
experimental_model
Choline tracer, microbial culture, microbiome transfer and atherosclerosis models
exposure
Choline-supplemented chow and berberine; deuterated choline tracing
limitations
Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia
plain_language
The community abundance of metabolic genes changed; direct inhibition of each encoded enzyme was not established.
primary_references
[berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
tissue_or_cell_type
Microbial choline metabolism
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1104–1115
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Choline tracer, microbial culture, microbiome transfer and atherosclerosis models · source_derived_draft · unverified_draft
### berberine-microbial-genes Metagenomics identified altered cutC/cntA abundance alongside changes in microbial composition after berberine. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The community abundance of metabolic genes changed; direct inhibition of each encoded enzyme was not established. organism: C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia tissue_or_cell_type: Microbial choline metabolism experimental_model: Choline tracer, microbial culture, microbiome transfer and atherosclerosis models limitations: Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake. exposure: Choline-supplemented chow and berberine; deuterated choline tracing evidence_span: {"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"} [berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
Complete structured claim and evidence
Berberine reduced atherosclerotic lesion area in choline-fed ApoE-knockout mice.
Berberine → Atherosclerotic lesion area source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"}
experimental_model
Choline tracer, microbial culture, microbiome transfer and atherosclerosis models
exposure
Choline-supplemented chow and berberine; deuterated choline tracing
limitations
Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia
plain_language
This is an animal disease outcome, separate from the microbial reaction records.
primary_references
[berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
tissue_or_cell_type
Microbial choline metabolism
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1117–1128
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Choline tracer, microbial culture, microbiome transfer and atherosclerosis models · source_derived_draft · unverified_draft
### berberine-plaque-mice Berberine reduced atherosclerotic lesion area in choline-fed ApoE-knockout mice. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This is an animal disease outcome, separate from the microbial reaction records. organism: C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia tissue_or_cell_type: Microbial choline metabolism experimental_model: Choline tracer, microbial culture, microbiome transfer and atherosclerosis models limitations: Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake. exposure: Choline-supplemented chow and berberine; deuterated choline tracing evidence_span: {"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"} [berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
Complete structured claim and evidence
The berberine-plus-probiotics arm had an HbA1c change of -1.04 percentage points compared with -0.99 for berberine alone.
Berberine → Glycated hemoglobin / HbA1c concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/33024120.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9", "start_char": 0, "end_char": 1283, "text_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9"}
experimental_model
Multicenter randomized double-blind four-arm trial with metagenomics and microbial validation
exposure
Twelve weeks of berberine, probiotics, both or placebo after one week of gentamycin pretreatment
limitations
Antibiotic run-in and Chinese drug-naive population limit generalization. Microbial mediation is supported but not proof it explains every effect. Probiotic addition did not show a clear extra HbA1c reduction in the reported estimates.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
409 newly diagnosed type 2 diabetes patients; separate bacterial experiments
plain_language
These results do not demonstrate a large added benefit from this probiotic mixture.
primary_references
[berberine-p33024120] Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). (2020). https://pubmed.ncbi.nlm.nih.gov/33024120/ DOI: 10.1038/s41467-020-18414-8
tissue_or_cell_type
Glycemia, gut microbiome and bile-acid transformation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1143–1154
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter randomized double-blind four-arm trial with metagenomics and microbial validation · source_derived_draft · unverified_draft
### berberine-premote-probiotics The berberine-plus-probiotics arm had an HbA1c change of -1.04 percentage points compared with -0.99 for berberine alone. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: These results do not demonstrate a large added benefit from this probiotic mixture. organism: 409 newly diagnosed type 2 diabetes patients; separate bacterial experiments tissue_or_cell_type: Glycemia, gut microbiome and bile-acid transformation experimental_model: Multicenter randomized double-blind four-arm trial with metagenomics and microbial validation limitations: Antibiotic run-in and Chinese drug-naive population limit generalization. Microbial mediation is supported but not proof it explains every effect. Probiotic addition did not show a clear extra HbA1c reduction in the reported estimates. exposure: Twelve weeks of berberine, probiotics, both or placebo after one week of gentamycin pretreatment evidence_span: {"source_cache": "artifacts/berberine-research/33024120.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9", "start_char": 0, "end_char": 1283, "text_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9"} [berberine-p33024120] Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). (2020). https://pubmed.ncbi.nlm.nih.gov/33024120/ DOI: 10.1038/s41467-020-18414-8
Complete structured claim and evidence
The authors linked berberine-associated glycemic improvement to inhibited Ruminococcus bromii-associated DCA biotransformation using metagenomic, metabolomic and culture evidence.
Berberine → Ruminococcus bromii-associated deoxycholic acid biotransformation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/33024120.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9", "start_char": 0, "end_char": 1283, "text_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9"}
experimental_model
Multicenter randomized double-blind four-arm trial with metagenomics and microbial validation
exposure
Twelve weeks of berberine, probiotics, both or placebo after one week of gentamycin pretreatment
limitations
Antibiotic run-in and Chinese drug-naive population limit generalization. Microbial mediation is supported but not proof it explains every effect. Probiotic addition did not show a clear extra HbA1c reduction in the reported estimates.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
409 newly diagnosed type 2 diabetes patients; separate bacterial experiments
plain_language
Gut microbes and bile-acid metabolism form another supported branch, with mediation uncertainty retained.
primary_references
[berberine-p33024120] Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). (2020). https://pubmed.ncbi.nlm.nih.gov/33024120/ DOI: 10.1038/s41467-020-18414-8
tissue_or_cell_type
Glycemia, gut microbiome and bile-acid transformation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1156–1167
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter randomized double-blind four-arm trial with metagenomics and microbial validation · source_derived_draft · unverified_draft
### berberine-premote-dca The authors linked berberine-associated glycemic improvement to inhibited Ruminococcus bromii-associated DCA biotransformation using metagenomic, metabolomic and culture evidence. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Gut microbes and bile-acid metabolism form another supported branch, with mediation uncertainty retained. organism: 409 newly diagnosed type 2 diabetes patients; separate bacterial experiments tissue_or_cell_type: Glycemia, gut microbiome and bile-acid transformation experimental_model: Multicenter randomized double-blind four-arm trial with metagenomics and microbial validation limitations: Antibiotic run-in and Chinese drug-naive population limit generalization. Microbial mediation is supported but not proof it explains every effect. Probiotic addition did not show a clear extra HbA1c reduction in the reported estimates. exposure: Twelve weeks of berberine, probiotics, both or placebo after one week of gentamycin pretreatment evidence_span: {"source_cache": "artifacts/berberine-research/33024120.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9", "start_char": 0, "end_char": 1283, "text_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9"} [berberine-p33024120] Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). (2020). https://pubmed.ncbi.nlm.nih.gov/33024120/ DOI: 10.1038/s41467-020-18414-8
Complete structured claim and evidence
Gastrointestinal side effects were more frequent with berberine in PREMOTE.
Berberine → Gastrointestinal adverse events source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/33024120.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9", "start_char": 0, "end_char": 1283, "text_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9"}
experimental_model
Multicenter randomized double-blind four-arm trial with metagenomics and microbial validation
exposure
Twelve weeks of berberine, probiotics, both or placebo after one week of gentamycin pretreatment
limitations
Antibiotic run-in and Chinese drug-naive population limit generalization. Microbial mediation is supported but not proof it explains every effect. Probiotic addition did not show a clear extra HbA1c reduction in the reported estimates.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
409 newly diagnosed type 2 diabetes patients; separate bacterial experiments
plain_language
Clinical benefits and tolerability are recorded separately.
primary_references
[berberine-p33024120] Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). (2020). https://pubmed.ncbi.nlm.nih.gov/33024120/ DOI: 10.1038/s41467-020-18414-8
tissue_or_cell_type
Glycemia, gut microbiome and bile-acid transformation
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1169–1180
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter randomized double-blind four-arm trial with metagenomics and microbial validation · source_derived_draft · unverified_draft
### berberine-premote-gi Gastrointestinal side effects were more frequent with berberine in PREMOTE. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Clinical benefits and tolerability are recorded separately. organism: 409 newly diagnosed type 2 diabetes patients; separate bacterial experiments tissue_or_cell_type: Glycemia, gut microbiome and bile-acid transformation experimental_model: Multicenter randomized double-blind four-arm trial with metagenomics and microbial validation limitations: Antibiotic run-in and Chinese drug-naive population limit generalization. Microbial mediation is supported but not proof it explains every effect. Probiotic addition did not show a clear extra HbA1c reduction in the reported estimates. exposure: Twelve weeks of berberine, probiotics, both or placebo after one week of gentamycin pretreatment evidence_span: {"source_cache": "artifacts/berberine-research/33024120.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9", "start_char": 0, "end_char": 1283, "text_sha256": "5dbbfd240d55ac62d2f48263f25e5543e47aa4a91d7711637fbacc543ce54bd9"} [berberine-p33024120] Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). (2020). https://pubmed.ncbi.nlm.nih.gov/33024120/ DOI: 10.1038/s41467-020-18414-8
Complete structured claim and evidence
Berberine lowered HbA1c from 7.5% to 6.6% in its treatment arm, with a significant difference from placebo.
Berberine → Glycated hemoglobin / HbA1c concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/18397984.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0711d6853427d4b78af4704fd7630e08ed0f83d599311156dbc8570efd88dce2", "start_char": 0, "end_char": 1715, "text_sha256": "0711d6853427d4b78af4704fd7630e08ed0f83d599311156dbc8570efd88dce2"}
experimental_model
Randomized placebo-controlled clinical trial
exposure
Berberine 1 g/day for three months
limitations
Short trial with surrogate endpoints. Within-arm clamp improvement was not statistically significant versus placebo; lower glucose does not identify one causal enzyme.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
116 people with type 2 diabetes and dyslipidemia
plain_language
This trial measured improved glycemic control in people with diabetes.
primary_references
[berberine-p18397984] Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. (2008). https://pubmed.ncbi.nlm.nih.gov/18397984/ DOI: 10.1210/jc.2007-2404
tissue_or_cell_type
Glycemic markers, lipids and insulin sensitivity
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1182–1193
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled clinical trial · source_derived_draft · unverified_draft
### berberine-diabetes-hba1c Berberine lowered HbA1c from 7.5% to 6.6% in its treatment arm, with a significant difference from placebo. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This trial measured improved glycemic control in people with diabetes. organism: 116 people with type 2 diabetes and dyslipidemia tissue_or_cell_type: Glycemic markers, lipids and insulin sensitivity experimental_model: Randomized placebo-controlled clinical trial limitations: Short trial with surrogate endpoints. Within-arm clamp improvement was not statistically significant versus placebo; lower glucose does not identify one causal enzyme. exposure: Berberine 1 g/day for three months evidence_span: {"source_cache": "artifacts/berberine-research/18397984.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0711d6853427d4b78af4704fd7630e08ed0f83d599311156dbc8570efd88dce2", "start_char": 0, "end_char": 1715, "text_sha256": "0711d6853427d4b78af4704fd7630e08ed0f83d599311156dbc8570efd88dce2"} [berberine-p18397984] Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. (2008). https://pubmed.ncbi.nlm.nih.gov/18397984/ DOI: 10.1210/jc.2007-2404
Complete structured claim and evidence
LDL cholesterol fell from 3.23 to 2.55 mmol/L in the berberine arm and differed significantly from placebo.
Berberine → LDL cholesterol concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/18397984.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0711d6853427d4b78af4704fd7630e08ed0f83d599311156dbc8570efd88dce2", "start_char": 0, "end_char": 1715, "text_sha256": "0711d6853427d4b78af4704fd7630e08ed0f83d599311156dbc8570efd88dce2"}
experimental_model
Randomized placebo-controlled clinical trial
exposure
Berberine 1 g/day for three months
limitations
Short trial with surrogate endpoints. Within-arm clamp improvement was not statistically significant versus placebo; lower glucose does not identify one causal enzyme.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
116 people with type 2 diabetes and dyslipidemia
plain_language
The lipid endpoint was measured independently of glucose.
primary_references
[berberine-p18397984] Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. (2008). https://pubmed.ncbi.nlm.nih.gov/18397984/ DOI: 10.1210/jc.2007-2404
tissue_or_cell_type
Glycemic markers, lipids and insulin sensitivity
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1195–1206
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled clinical trial · source_derived_draft · unverified_draft
### berberine-diabetes-ldl LDL cholesterol fell from 3.23 to 2.55 mmol/L in the berberine arm and differed significantly from placebo. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The lipid endpoint was measured independently of glucose. organism: 116 people with type 2 diabetes and dyslipidemia tissue_or_cell_type: Glycemic markers, lipids and insulin sensitivity experimental_model: Randomized placebo-controlled clinical trial limitations: Short trial with surrogate endpoints. Within-arm clamp improvement was not statistically significant versus placebo; lower glucose does not identify one causal enzyme. exposure: Berberine 1 g/day for three months evidence_span: {"source_cache": "artifacts/berberine-research/18397984.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0711d6853427d4b78af4704fd7630e08ed0f83d599311156dbc8570efd88dce2", "start_char": 0, "end_char": 1715, "text_sha256": "0711d6853427d4b78af4704fd7630e08ed0f83d599311156dbc8570efd88dce2"} [berberine-p18397984] Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. (2008). https://pubmed.ncbi.nlm.nih.gov/18397984/ DOI: 10.1210/jc.2007-2404
Complete structured claim and evidence
The between-group difference in clamp glucose disposal was not statistically significant, with P=0.063.
Berberine → Insulin-stimulated glucose disposal source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/18397984.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0711d6853427d4b78af4704fd7630e08ed0f83d599311156dbc8570efd88dce2", "start_char": 0, "end_char": 1715, "text_sha256": "0711d6853427d4b78af4704fd7630e08ed0f83d599311156dbc8570efd88dce2"}
experimental_model
Randomized placebo-controlled clinical trial
exposure
Berberine 1 g/day for three months
limitations
Short trial with surrogate endpoints. Within-arm clamp improvement was not statistically significant versus placebo; lower glucose does not identify one causal enzyme.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
116 people with type 2 diabetes and dyslipidemia
plain_language
A positive change within one group did not establish superiority on this insulin-sensitivity endpoint.
primary_references
[berberine-p18397984] Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. (2008). https://pubmed.ncbi.nlm.nih.gov/18397984/ DOI: 10.1210/jc.2007-2404
tissue_or_cell_type
Glycemic markers, lipids and insulin sensitivity
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1208–1219
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled clinical trial · source_derived_draft · unverified_draft
### berberine-diabetes-clamp-null The between-group difference in clamp glucose disposal was not statistically significant, with P=0.063. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A positive change within one group did not establish superiority on this insulin-sensitivity endpoint. organism: 116 people with type 2 diabetes and dyslipidemia tissue_or_cell_type: Glycemic markers, lipids and insulin sensitivity experimental_model: Randomized placebo-controlled clinical trial limitations: Short trial with surrogate endpoints. Within-arm clamp improvement was not statistically significant versus placebo; lower glucose does not identify one causal enzyme. exposure: Berberine 1 g/day for three months evidence_span: {"source_cache": "artifacts/berberine-research/18397984.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0711d6853427d4b78af4704fd7630e08ed0f83d599311156dbc8570efd88dce2", "start_char": 0, "end_char": 1715, "text_sha256": "0711d6853427d4b78af4704fd7630e08ed0f83d599311156dbc8570efd88dce2"} [berberine-p18397984] Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. (2008). https://pubmed.ncbi.nlm.nih.gov/18397984/ DOI: 10.1210/jc.2007-2404
Complete structured claim and evidence
A 36-person pilot reported similar glucose-lowering responses in berberine and metformin groups.
Berberine → Glycated hemoglobin / HbA1c concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/18442638.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d85d3f03994b65869cd6c52fb46d679f220e4221a6764b38833468818551b66", "start_char": 0, "end_char": 1655, "text_sha256": "0d85d3f03994b65869cd6c52fb46d679f220e4221a6764b38833468818551b66"}
experimental_model
Small randomized comparison plus uncontrolled add-on cohort
exposure
Three-month berberine/metformin comparison and berberine add-on study
limitations
Small pilot, not an equivalence trial proving berberine substitutes for metformin. Add-on cohort lacks a concurrent placebo comparison.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Adults with type 2 diabetes
plain_language
A small comparison is encouraging but does not establish interchangeable clinical treatment.
primary_references
[berberine-p18442638] Efficacy of berberine in patients with type 2 diabetes mellitus. (2008). https://pubmed.ncbi.nlm.nih.gov/18442638/ DOI: 10.1016/j.metabol.2008.01.013
tissue_or_cell_type
Glycemic control and gastrointestinal effects
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1221–1232
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Small randomized comparison plus uncontrolled add-on cohort · source_derived_draft · unverified_draft
### berberine-pilot-metformin A 36-person pilot reported similar glucose-lowering responses in berberine and metformin groups. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A small comparison is encouraging but does not establish interchangeable clinical treatment. organism: Adults with type 2 diabetes tissue_or_cell_type: Glycemic control and gastrointestinal effects experimental_model: Small randomized comparison plus uncontrolled add-on cohort limitations: Small pilot, not an equivalence trial proving berberine substitutes for metformin. Add-on cohort lacks a concurrent placebo comparison. exposure: Three-month berberine/metformin comparison and berberine add-on study evidence_span: {"source_cache": "artifacts/berberine-research/18442638.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d85d3f03994b65869cd6c52fb46d679f220e4221a6764b38833468818551b66", "start_char": 0, "end_char": 1655, "text_sha256": "0d85d3f03994b65869cd6c52fb46d679f220e4221a6764b38833468818551b66"} [berberine-p18442638] Efficacy of berberine in patients with type 2 diabetes mellitus. (2008). https://pubmed.ncbi.nlm.nih.gov/18442638/ DOI: 10.1016/j.metabol.2008.01.013
Complete structured claim and evidence
The pilot report described transient gastrointestinal adverse effects in 20 patients, reported as 34.5%.
Berberine → Gastrointestinal adverse events source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/18442638.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d85d3f03994b65869cd6c52fb46d679f220e4221a6764b38833468818551b66", "start_char": 0, "end_char": 1655, "text_sha256": "0d85d3f03994b65869cd6c52fb46d679f220e4221a6764b38833468818551b66"}
experimental_model
Small randomized comparison plus uncontrolled add-on cohort
exposure
Three-month berberine/metformin comparison and berberine add-on study
limitations
Small pilot, not an equivalence trial proving berberine substitutes for metformin. Add-on cohort lacks a concurrent placebo comparison.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Adults with type 2 diabetes
plain_language
Digestive effects were common enough to be recorded explicitly.
primary_references
[berberine-p18442638] Efficacy of berberine in patients with type 2 diabetes mellitus. (2008). https://pubmed.ncbi.nlm.nih.gov/18442638/ DOI: 10.1016/j.metabol.2008.01.013
tissue_or_cell_type
Glycemic control and gastrointestinal effects
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1234–1245
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Small randomized comparison plus uncontrolled add-on cohort · source_derived_draft · unverified_draft
### berberine-pilot-gi The pilot report described transient gastrointestinal adverse effects in 20 patients, reported as 34.5%. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Digestive effects were common enough to be recorded explicitly. organism: Adults with type 2 diabetes tissue_or_cell_type: Glycemic control and gastrointestinal effects experimental_model: Small randomized comparison plus uncontrolled add-on cohort limitations: Small pilot, not an equivalence trial proving berberine substitutes for metformin. Add-on cohort lacks a concurrent placebo comparison. exposure: Three-month berberine/metformin comparison and berberine add-on study evidence_span: {"source_cache": "artifacts/berberine-research/18442638.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d85d3f03994b65869cd6c52fb46d679f220e4221a6764b38833468818551b66", "start_char": 0, "end_char": 1655, "text_sha256": "0d85d3f03994b65869cd6c52fb46d679f220e4221a6764b38833468818551b66"} [berberine-p18442638] Efficacy of berberine in patients with type 2 diabetes mellitus. (2008). https://pubmed.ncbi.nlm.nih.gov/18442638/ DOI: 10.1016/j.metabol.2008.01.013
Complete structured claim and evidence
Berberine did not reduce visceral adipose area versus placebo; the between-group estimate was 1.4% with 97.5% CI -2.4% to 5.2%.
Berberine → Visceral adipose tissue area source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/41543854.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021", "start_char": 0, "end_char": 2354, "text_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021"}
experimental_model
Multicenter double-blind randomized placebo-controlled trial
exposure
Berberine 1 g/day for six months
limitations
No significant primary fat-reduction effect. Lipid endpoints were secondary; this population differs from diabetes trials and does not resolve every liver-disease subgroup.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
337 diabetes-free adults with obesity and MASLD in China
plain_language
The trial did not show the expected visceral-fat benefit.
primary_references
[berberine-p41543854] Berberine and Adiposity in Diabetes-Free Individuals With Obesity and MASLD: A Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41543854/ DOI: 10.1001/jamanetworkopen.2025.54152
tissue_or_cell_type
CT visceral adipose area and liver fat; lipid endpoints
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1247–1258
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter double-blind randomized placebo-controlled trial · source_derived_draft · unverified_draft
### berberine-masld-visceral-null Berberine did not reduce visceral adipose area versus placebo; the between-group estimate was 1.4% with 97.5% CI -2.4% to 5.2%. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial did not show the expected visceral-fat benefit. organism: 337 diabetes-free adults with obesity and MASLD in China tissue_or_cell_type: CT visceral adipose area and liver fat; lipid endpoints experimental_model: Multicenter double-blind randomized placebo-controlled trial limitations: No significant primary fat-reduction effect. Lipid endpoints were secondary; this population differs from diabetes trials and does not resolve every liver-disease subgroup. exposure: Berberine 1 g/day for six months evidence_span: {"source_cache": "artifacts/berberine-research/41543854.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021", "start_char": 0, "end_char": 2354, "text_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021"} [berberine-p41543854] Berberine and Adiposity in Diabetes-Free Individuals With Obesity and MASLD: A Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41543854/ DOI: 10.1001/jamanetworkopen.2025.54152
Complete structured claim and evidence
LDL cholesterol fell by an additional 7.72 mg/dL with berberine versus placebo, a secondary endpoint.
Berberine → LDL cholesterol concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/41543854.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021", "start_char": 0, "end_char": 2354, "text_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021"}
experimental_model
Multicenter double-blind randomized placebo-controlled trial
exposure
Berberine 1 g/day for six months
limitations
No significant primary fat-reduction effect. Lipid endpoints were secondary; this population differs from diabetes trials and does not resolve every liver-disease subgroup.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
337 diabetes-free adults with obesity and MASLD in China
plain_language
A modest lipid effect can coexist with negative fat-reduction endpoints.
primary_references
[berberine-p41543854] Berberine and Adiposity in Diabetes-Free Individuals With Obesity and MASLD: A Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41543854/ DOI: 10.1001/jamanetworkopen.2025.54152
tissue_or_cell_type
CT visceral adipose area and liver fat; lipid endpoints
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1273–1284
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter double-blind randomized placebo-controlled trial · source_derived_draft · unverified_draft
### berberine-masld-ldl LDL cholesterol fell by an additional 7.72 mg/dL with berberine versus placebo, a secondary endpoint. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A modest lipid effect can coexist with negative fat-reduction endpoints. organism: 337 diabetes-free adults with obesity and MASLD in China tissue_or_cell_type: CT visceral adipose area and liver fat; lipid endpoints experimental_model: Multicenter double-blind randomized placebo-controlled trial limitations: No significant primary fat-reduction effect. Lipid endpoints were secondary; this population differs from diabetes trials and does not resolve every liver-disease subgroup. exposure: Berberine 1 g/day for six months evidence_span: {"source_cache": "artifacts/berberine-research/41543854.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021", "start_char": 0, "end_char": 2354, "text_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021"} [berberine-p41543854] Berberine and Adiposity in Diabetes-Free Individuals With Obesity and MASLD: A Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41543854/ DOI: 10.1001/jamanetworkopen.2025.54152
Complete structured claim and evidence
Apolipoprotein B fell by an additional 3.42 mg/dL with berberine versus placebo, a secondary endpoint.
Berberine → Circulating apolipoprotein B concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/41543854.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021", "start_char": 0, "end_char": 2354, "text_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021"}
experimental_model
Multicenter double-blind randomized placebo-controlled trial
exposure
Berberine 1 g/day for six months
limitations
No significant primary fat-reduction effect. Lipid endpoints were secondary; this population differs from diabetes trials and does not resolve every liver-disease subgroup.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
337 diabetes-free adults with obesity and MASLD in China
plain_language
A separate lipoprotein marker changed; cardiovascular events were not the outcome.
primary_references
[berberine-p41543854] Berberine and Adiposity in Diabetes-Free Individuals With Obesity and MASLD: A Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41543854/ DOI: 10.1001/jamanetworkopen.2025.54152
tissue_or_cell_type
CT visceral adipose area and liver fat; lipid endpoints
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1286–1297
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter double-blind randomized placebo-controlled trial · source_derived_draft · unverified_draft
### berberine-masld-apob Apolipoprotein B fell by an additional 3.42 mg/dL with berberine versus placebo, a secondary endpoint. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate lipoprotein marker changed; cardiovascular events were not the outcome. organism: 337 diabetes-free adults with obesity and MASLD in China tissue_or_cell_type: CT visceral adipose area and liver fat; lipid endpoints experimental_model: Multicenter double-blind randomized placebo-controlled trial limitations: No significant primary fat-reduction effect. Lipid endpoints were secondary; this population differs from diabetes trials and does not resolve every liver-disease subgroup. exposure: Berberine 1 g/day for six months evidence_span: {"source_cache": "artifacts/berberine-research/41543854.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021", "start_char": 0, "end_char": 2354, "text_sha256": "1093df47a715746d0334d7d7f3c9c0c71e502b43b47b383b21900b982d6ad021"} [berberine-p41543854] Berberine and Adiposity in Diabetes-Free Individuals With Obesity and MASLD: A Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41543854/ DOI: 10.1001/jamanetworkopen.2025.54152
Complete structured claim and evidence
No colorectal cancers were detected during follow-up in either trial group.
Berberine → Colorectal cancer incidence source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/31926918.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0045a39cfd796c9db7aa81e0a9c4bea8004396e137d842519e03664560c4878c", "start_char": 0, "end_char": 2466, "text_sha256": "0045a39cfd796c9db7aa81e0a9c4bea8004396e137d842519e03664560c4878c"}
experimental_model
Multicenter double-blind randomized placebo-controlled trial
exposure
Berberine 0.3 g twice daily; colonoscopy follow-up up to two years
limitations
Modified intention-to-treat analysis excluded participants without efficacy data. Adenoma recurrence is not colorectal-cancer mortality or proof of cancer treatment.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Adults after colorectal polypectomy; 1108 randomized, 891 in full analysis
plain_language
Zero observed cancers do not establish a cancer-prevention effect.
primary_references
[berberine-p31926918] Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study. (2020). https://pubmed.ncbi.nlm.nih.gov/31926918/ DOI: 10.1016/s2468-1253(19)30409-1
tissue_or_cell_type
Adenoma recurrence
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1312–1323
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter double-blind randomized placebo-controlled trial · source_derived_draft · unverified_draft
### berberine-adenoma-cancer-null No colorectal cancers were detected during follow-up in either trial group. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zero observed cancers do not establish a cancer-prevention effect. organism: Adults after colorectal polypectomy; 1108 randomized, 891 in full analysis tissue_or_cell_type: Adenoma recurrence experimental_model: Multicenter double-blind randomized placebo-controlled trial limitations: Modified intention-to-treat analysis excluded participants without efficacy data. Adenoma recurrence is not colorectal-cancer mortality or proof of cancer treatment. exposure: Berberine 0.3 g twice daily; colonoscopy follow-up up to two years evidence_span: {"source_cache": "artifacts/berberine-research/31926918.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0045a39cfd796c9db7aa81e0a9c4bea8004396e137d842519e03664560c4878c", "start_char": 0, "end_char": 2466, "text_sha256": "0045a39cfd796c9db7aa81e0a9c4bea8004396e137d842519e03664560c4878c"} [berberine-p31926918] Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study. (2020). https://pubmed.ncbi.nlm.nih.gov/31926918/ DOI: 10.1016/s2468-1253(19)30409-1
Complete structured claim and evidence
Post-treatment follow-up reported adenoma recurrence of 34.7% after prior berberine assignment versus 52.1% after prior placebo.
Berberine → Colorectal adenoma recurrence source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/40795846.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1df2fd3eb5e8daef204f50dac917098b8c4be324d6e5d3a85b7aa3a9385ffc24", "start_char": 0, "end_char": 983, "text_sha256": "1df2fd3eb5e8daef204f50dac917098b8c4be324d6e5d3a85b7aa3a9385ffc24"}
experimental_model
Retrospective post-treatment follow-up of the previous randomized trial
exposure
Up to six years after treatment cessation
limitations
This is follow-up of the same original trial, not an independent randomized trial; post-trial selection and surveillance can affect estimates.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
781 recruited from the earlier cohort; 648 underwent follow-up colonoscopy
plain_language
The long follow-up is useful, while its observational phase and shared participants remain explicit.
primary_references
[berberine-p40795846] Berberine for preventing colorectal adenoma recurrence and neoplasm occurrence: 6-Year follow-up of a randomized clinical trial. (2025). https://pubmed.ncbi.nlm.nih.gov/40795846/ DOI: 10.1016/j.xcrm.2025.102293
tissue_or_cell_type
Long-term adenoma recurrence
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1325–1336
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retrospective post-treatment follow-up of the previous randomized trial · source_derived_draft · unverified_draft
### berberine-adenoma-followup Post-treatment follow-up reported adenoma recurrence of 34.7% after prior berberine assignment versus 52.1% after prior placebo. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The long follow-up is useful, while its observational phase and shared participants remain explicit. organism: 781 recruited from the earlier cohort; 648 underwent follow-up colonoscopy tissue_or_cell_type: Long-term adenoma recurrence experimental_model: Retrospective post-treatment follow-up of the previous randomized trial limitations: This is follow-up of the same original trial, not an independent randomized trial; post-trial selection and surveillance can affect estimates. exposure: Up to six years after treatment cessation evidence_span: {"source_cache": "artifacts/berberine-research/40795846.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1df2fd3eb5e8daef204f50dac917098b8c4be324d6e5d3a85b7aa3a9385ffc24", "start_char": 0, "end_char": 983, "text_sha256": "1df2fd3eb5e8daef204f50dac917098b8c4be324d6e5d3a85b7aa3a9385ffc24"} [berberine-p40795846] Berberine for preventing colorectal adenoma recurrence and neoplasm occurrence: 6-Year follow-up of a randomized clinical trial. (2025). https://pubmed.ncbi.nlm.nih.gov/40795846/ DOI: 10.1016/j.xcrm.2025.102293
Complete structured claim and evidence
Complex I transferred electrons from NADH to ubiquinone-10 in reconstituted membranes.
Mitochondrial respiratory complex I → Ubiquinone-10 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coq10-research/29133414.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d", "start_char": 0, "end_char": 1770, "text_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d"}
experimental_model
Proteoliposome enzyme kinetics
exposure
Ubiquinones with one to ten isoprenoid units
limitations
Purified enzyme system; short-chain analogues do not have identical binding and release kinetics to Q10.
nutrient_topic
Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
organism
Mammalian complex I preparation
plain_language
CoQ receives electrons from the first respiratory complex.
primary_references
[coq10-p29133414] Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I. (2017). https://pubmed.ncbi.nlm.nih.gov/29133414/ DOI: 10.1073/pnas.1714074114
tissue_or_cell_type
Membrane quinone channel
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 385–396
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Proteoliposome enzyme kinetics · source_derived_draft · unverified_draft
### coq10-complex-i-q Complex I transferred electrons from NADH to ubiquinone-10 in reconstituted membranes. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CoQ receives electrons from the first respiratory complex. organism: Mammalian complex I preparation tissue_or_cell_type: Membrane quinone channel experimental_model: Proteoliposome enzyme kinetics limitations: Purified enzyme system; short-chain analogues do not have identical binding and release kinetics to Q10. exposure: Ubiquinones with one to ten isoprenoid units evidence_span: {"source_cache": "artifacts/coq10-research/29133414.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d", "start_char": 0, "end_char": 1770, "text_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d"} [coq10-p29133414] Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I. (2017). https://pubmed.ncbi.nlm.nih.gov/29133414/ DOI: 10.1073/pnas.1714074114
Complete structured claim and evidence
FMN restored rotenone-sensitive NADH:quinone reductase activity after alkaline reductive inactivation of bovine membrane-bound complex I.
Flavin mononucleotide → Mitochondrial respiratory complex I source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 19, "char_start": 0, "char_end": 1242, "evidence_access": "full-text"}]
experimental_model
Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.
exposure
10 micromolar FMN after NADH/respiratory blockade at pH 10.
limitations
pH 10 treatment; not a test of dietary deficiency or oral supplementation.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Bos taurus
plain_language
Putting the correct flavin back restored this experimentally inactivated respiratory enzyme.
primary_references
[gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048
tissue_or_cell_type
Heart submitochondrial particles
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 570–581
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. · source_derived_draft · unverified_draft
### b2-met-complex-i-fmn-reconstitution FMN restored rotenone-sensitive NADH:quinone reductase activity after alkaline reductive inactivation of bovine membrane-bound complex I. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Putting the correct flavin back restored this experimentally inactivated respiratory enzyme. organism: Bos taurus tissue_or_cell_type: Heart submitochondrial particles experimental_model: Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. limitations: pH 10 treatment; not a test of dietary deficiency or oral supplementation. exposure: 10 micromolar FMN after NADH/respiratory blockade at pH 10. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 19, "char_start": 0, "char_end": 1242, "evidence_access": "full-text"}] [gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048
Complete structured claim and evidence
Riboflavin-free culture reduced complex I abundance; human 143B proteomics identified particularly strong loss of its NADH-oxidizing N-module subunits.
Riboflavin (vitamin B2) → Mitochondrial respiratory complex I source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}]
experimental_model
Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions.
exposure
Riboflavin-free medium; matched control contained 1 micromolar riboflavin.
limitations
Cell-culture withdrawal; proteomic abundance does not establish a human blood threshold.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens; Mus musculus
plain_language
Removing B2 reduced parts needed to build the respiratory enzyme.
primary_references
[curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001
tissue_or_cell_type
143B cells and mouse adult fibroblasts
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 609–620
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. · source_derived_draft · unverified_draft
### b2-met-depletion-complex-i Riboflavin-free culture reduced complex I abundance; human 143B proteomics identified particularly strong loss of its NADH-oxidizing N-module subunits. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing B2 reduced parts needed to build the respiratory enzyme. organism: Homo sapiens; Mus musculus tissue_or_cell_type: 143B cells and mouse adult fibroblasts experimental_model: Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. limitations: Cell-culture withdrawal; proteomic abundance does not establish a human blood threshold. exposure: Riboflavin-free medium; matched control contained 1 micromolar riboflavin. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}] [curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001
Complete structured claim and evidence
Mitochondrial ACP knockdown in HEK293T cells subsequently reduced respiratory complex I specific activity.
Human mitochondrial acyl carrier protein / NDUFAB1 → Mitochondrial respiratory complex I source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Abstract, later phenotypic changes
experimental_model
Mitochondrial ACP siRNA in HEK293T cells
exposure
ACP mRNA and protein reduced by more than 85% within 24 hours; later measurements followed knockdown.
limitations
Temporal ordering alone does not separate all direct complex-I effects from secondary cellular injury; abstract-level extraction. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
The carrier-protein defect also impaired complex I function.
primary_references
[b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200
tissue_or_cell_type
HEK293T mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 837–849
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mitochondrial ACP siRNA in HEK293T cells · source_derived_draft · unverified_draft
### b5-met-mtacp-complex-i Mitochondrial ACP knockdown in HEK293T cells subsequently reduced respiratory complex I specific activity. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier-protein defect also impaired complex I function. organism: Homo sapiens tissue_or_cell_type: HEK293T mitochondria experimental_model: Mitochondrial ACP siRNA in HEK293T cells limitations: Temporal ordering alone does not separate all direct complex-I effects from secondary cellular injury; abstract-level extraction. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: ACP mRNA and protein reduced by more than 85% within 24 hours; later measurements followed knockdown. cross_nutrient: false evidence_location: Abstract, later phenotypic changes [b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200
Complete structured claim and evidence
Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis.
Riboflavin kinase / RFK → Riboflavin (vitamin B2) source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract and product-bound structure
experimental_model
Human RFK structural and catalytic mechanism study
exposure
Purified RFK with flavin and adenine nucleotide ligands.
limitations
Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
RFK performs the first activation step from riboflavin to FMN.
primary_references
[transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
tissue_or_cell_type
Purified protein
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 293–304
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RFK structural and catalytic mechanism study · source_derived_draft · unverified_draft
### transport-rfk-phosphorylation Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFK performs the first activation step from riboflavin to FMN. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human RFK structural and catalytic mechanism study limitations: Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent. exposure: Purified RFK with flavin and adenine nucleotide ligands. evidence_location: Abstract and product-bound structure [transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
Complete structured claim and evidence
Conversion of N-desmethyltamoxifen to endoxifen was catalyzed by CYP2D6 in the tested system.
Human cytochrome P450 2D6 → N-Desmethyltamoxifen source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/15159443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081", "start_char": 0, "end_char": 1544, "text_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081"}
experimental_model
Kinetic, inhibition and recombinant-enzyme pathway mapping
exposure
Therapeutically relevant substrate concentrations
limitations
Biochemical pathway identity; does not attribute the observed DIM interaction to any single CYP or prove clinical cancer outcomes.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human liver microsomes and expressed CYPs
plain_language
The key activation step cannot be replaced by the statement that CYP1A2 is induced.
primary_references
[dim-p15159443] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. (2004). https://pubmed.ncbi.nlm.nih.gov/15159443/ DOI: 10.1124/jpet.104.065607
tissue_or_cell_type
Sequential tamoxifen metabolism
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1000–1011
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetic, inhibition and recombinant-enzyme pathway mapping · source_derived_draft · unverified_draft
### dim-tamoxifen-endoxifen Conversion of N-desmethyltamoxifen to endoxifen was catalyzed by CYP2D6 in the tested system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The key activation step cannot be replaced by the statement that CYP1A2 is induced. organism: Human liver microsomes and expressed CYPs tissue_or_cell_type: Sequential tamoxifen metabolism experimental_model: Kinetic, inhibition and recombinant-enzyme pathway mapping limitations: Biochemical pathway identity; does not attribute the observed DIM interaction to any single CYP or prove clinical cancer outcomes. exposure: Therapeutically relevant substrate concentrations evidence_span: {"source_cache": "artifacts/dim-research/15159443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081", "start_char": 0, "end_char": 1544, "text_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081"} [dim-p15159443] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. (2004). https://pubmed.ncbi.nlm.nih.gov/15159443/ DOI: 10.1124/jpet.104.065607
Complete structured claim and evidence

Availability and dependencies

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

Losing microbial conversion can reduce systemic exposure

Condition: machinery_impairment · Antibiotic depletion of gut bacteria in KK-Ay mice

Normal role: Gut microbes produce the more absorbable reduced form.

Recorded consequence: Less conversion and lower blood berberine; weaker lipid- and glucose-lowering effects.

Scope: Animal antibiotic perturbation, not dietary berberine deficiency

A transport defect can impair vitamin B1-dependent metabolism

Condition: machinery_impairment · Genetic Oct1 deletion in mice

Normal role: Mouse Oct1 contributes to hepatic thiamine supply.

Recorded consequence: Reduced activity of thiamine-dependent enzymes and disturbed glucose-fatty acid metabolism.

Scope: Mouse transporter deficiency; no berberine exposure in this causal comparison

A scaffold is needed for lysosomal AMPK activation

Condition: machinery_impairment · AXIN1 knockout in HCT-116 cells

Normal role: AXIN1 organizes the lysosomal signaling response.

Recorded consequence: Weakened lysosomal AMPK response to berberine.

Scope: Human cultured cells; experimental machinery loss

An insulin-sensitizing branch still needs an insulin receptor

Condition: machinery_impairment · INSR silencing in the cell experiments

Normal role: More INSR can enhance insulin-supported glucose consumption.

Recorded consequence: The berberine-enhanced glucose-consumption response was diminished.

Scope: Cultured-cell receptor loss; not dietary berberine deficiency

The microbial metabolite branch requires gut bacteria

Condition: machinery_impairment · Antibiotic pretreatment in animals

Normal role: Microbes make butyrate after oral berberine exposure.

Recorded consequence: Berberine no longer increased microbial butyrate production.

Scope: Animal microbial depletion; not an essential-nutrient deficiency

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Does clinically used berberine alter human hepatic thiamine supply through OCT1?Shared transport and inhibition of another substrate do not establish thiamine depletion. Species differences and the human OCT1 pharmacokinetic null result limit extrapolation.
Can riboflavin, niacin or CoQ10 status change the response to berberine?The compounds meet at respiratory machinery, but these separate studies do not test nutrient-by-berberine treatment interactions.
Which patients obtain durable clinical benefit beyond glucose or lipid biomarkers?Trial populations, formulations, comparators and endpoints differ. The null MASLD primary outcomes and positive diabetes or adenoma endpoints cannot be collapsed into a universal benefit.
How much does berberine alter endoxifen exposure or other CYP2D6-dependent activation pathways in patients?The human CYP2D6 probe result and a separate tamoxifen activation experiment form a hypothesis, not a measured berberine-tamoxifen interaction.
What is the net interaction between purified oral berberine and metformin in different human populations?Intravenous rats, oral rats, isolated-alkaloid mice and human goldenseal-mixture studies test different exposures; none supplies a universal direction or dose adjustment.
Which complex-I mechanism dominates at human tissue concentrations?Respiratory inhibition and AMPK responses are model dependent. A 2025 report proposes SIRT3-dependent NDUFS1 deacetylation and complex dissociation (PMID 40493314; https://pubmed.ncbi.nlm.nih.gov/40493314/); its accessible abstract does not resolve species for each protein experiment, so species-specific edges await full-method curation.
How does potassium or magnesium depletion modify berberine-associated electrophysiologic risk?The hERG studies identify a channel mechanism but do not quantify this nutrient-by-exposure interaction in people; do not infer a serum threshold from the assays.
How much of the berberine-cyclosporine exposure rise is transport and how much is metabolism?The ledger records the exposure rise and separately records berberine inhibiting CYP3A4 phenotypic activity. Neither apportions the effect.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Berberine

The mechanisms

Berberine increased the urinary dextromethorphan/dextrorphan ratio approximately ninefold, indicating reduced CYP2D6 activity.

Repeated berberine inhibited CYP3A4 phenotypic activity, with midazolam oral clearance reduced by 27%.

Final cyclosporine concentrations were 29.3% higher in the berberine-treated group than in the group without berberine.

Berberine inhibited respiration in L6 myotubes and muscle mitochondria through a complex-I-associated effect.

Berberine still increased glucose utilization after AMPK inhibition, AMPK-alpha silencing or dominant-negative AMPK expression.

Berberine increased LDLR expression through an ERK-dependent, SREBP-independent post-transcriptional mechanism in human hepatoma cells.

Human OCT1 transported thiamine with approximately 9.5-fold lower affinity than mouse Oct1.

Berberine inhibited choline-to-TMA conversion in bacterial cultures and gut consortia, including human fecal samples.

Berberine decreased forskolin-stimulated chloride secretion in T84 monolayers through a predominantly PKC-alpha-dependent pathway.

HbA1c changed by -0.99 percentage points with berberine alone versus -0.59 with placebo over 12 weeks.

Berberine did not reduce liver fat versus placebo; the between-group estimate was 0.9 percentage points with 97.5% CI -0.4 to 2.1.

Adenomas recurred in 36% of analyzed berberine participants versus 47% with placebo; relative risk 0.77, 95% CI 0.66-0.91.

Gut bacterial nitroreductases converted berberine to dihydroberberine.

Dihydroberberine had approximately fivefold greater intestinal absorption than berberine in the animal experiments.

Intestinal tissues converted dihydroberberine back to berberine; heat inactivation did not prevent conversion, supporting a nonenzymatic oxidation process.

Antibiotic depletion reduced berberine-to-dihydroberberine conversion and blood berberine in KK-Ay mice.

Human fecal nitroreductase activity correlated positively with blood berberine, with reported r=0.703.

Human OCT1 transported berberine in transfected cells, with reported Km 14.8 micromolar.

Human OCT2 transported berberine in transfected cells, with reported Km 4.4 micromolar.

OCT1/ABCB1 double-transfected cells transported berberine basolaterally to apically faster than single transfectants; zosuquidar inhibited apical efflux.

Berberine basolateral-to-apical flux exceeded absorptive flux by approximately 30-fold; P-glycoprotein substrates inhibited the secretory flux.

Poor OCT1 transporters did not show a difference in human berberine pharmacokinetics despite reduced uptake by variant OCT1 in vitro.

Female CYP2D6 poor metabolizers had an 80% lower M1-to-berberine ratio; the genotype effect was not found in males.

Female participants had 2.8-fold higher berberine AUC and 3.6-fold higher Cmax than males; CYP2D6 explained only part of the difference.

Oct1 deletion reduced hepatic thiamine-dependent enzyme activity, including pyruvate dehydrogenase, in mice.

Berberine increased AMPK phosphorylation in L6 myotubes.

Berberine increased lactate release in HepG2 and C2C12 cells, including during AMPK-pathway blockade.

Berberine activated lysosome-associated AMPK in an AXIN1-dependent, PEN2-independent manner in HCT-116 cells.

Berberine promoted UHRF1 degradation and reduced its expression.

Berberine reduced association between UHRF1 and AMPK alpha 1.

AXIN1 loss impaired the berberine response of lysosomal AMPK.

UHRF1 overexpression abolished berberine-induced AMPK activation in the tested cells.

Berberine stabilized LDLR mRNA through a regulatory region in its proximal 3-prime untranslated region.

Berberine accelerated ubiquitin-associated proteasomal degradation of HNF1A protein in HepG2 cells.

Berberine lowered HNF1A-dependent PCSK9 transcription; proteasome inhibition prevented this response.

Berberine increased INSR mRNA and protein in human liver cells through PKC-dependent promoter activation.

INSR silencing diminished the insulin-dependent increase in glucose consumption associated with berberine-enhanced receptor expression.

Berberine acutely increased GLUT1-mediated uptake in L929 cells and decreased apparent glucose-uptake Km without changing Vmax.

Berberine increased Nrf2 reporter activity in Caco-2 cells.

Berberine increased MDR1/ABCB1 expression; Nrf2 silencing abolished the gene response in Caco-2 cells.

Berberine inhibited a cAMP-dependent, chromanol-sensitive basolateral potassium current consistent with KCNQ1 by 88%.

Berberine did not affect apical chloride conductance in the permeabilized-cell experiments.

Berberine did not affect basolateral sodium-potassium ATPase activity in this model.

Berberine blocked hERG current, with IC50 about 3.1 micromolar in HEK293 cells and 80 micromolar in oocytes.

Berberine reduced hERG cell-surface abundance through mechanisms involving caveolin-1 and hERG S6 residues.

Berberine approximately doubled the losartan/E-3174 ratio, indicating reduced CYP2C9 activity.

No statistically significant change in caffeine probe pharmacokinetics was found after berberine.

No statistically significant change in omeprazole probe pharmacokinetics was found after berberine.

Midazolam AUC to infinity increased approximately 40% and Cmax 38% after repeated berberine.

In six transplant recipients, cyclosporine AUC rose 34.5% after 12 days of berberine.

The 3 mg/kg cyclosporine arm showed a 19.2% AUC increase with berberine.

The separate 6 mg/kg cyclosporine arm found no significant pharmacokinetic change after repeated berberine.

Berberine inhibited rat OCT1-mediated metformin uptake in transfected cells, with reported IC50 7.28 micromolar.

Berberine inhibited rat OCT2-mediated metformin uptake in transfected cells, with reported IC50 11.3 micromolar.

Intravenous berberine coadministration increased metformin AUC and reduced systemic clearance in rats.

Berberine inhibited rat OCT1-mediated metformin transport, with IC50 18.8 micromolar.

Berberine inhibited rat OCT2-mediated metformin transport, with IC50 1.02 micromolar.

Berberine inhibited rat MATE1-mediated metformin transport, with IC50 10.7 micromolar.

Oral berberine coadministration decreased metformin Cmax and AUC over the first four hours in rats.

Berberine increased kidney metformin concentration despite lower early plasma exposure in the oral rat study.

Goldenseal reduced metformin AUC by 23% without changing its half-life or renal clearance.

Goldenseal extract inhibited OCT3-mediated metformin transport in transfected cells.

Goldenseal extract inhibited PMAT-mediated metformin transport in transfected cells.

Goldenseal extract inhibited THTR2-mediated metformin transport in transfected cells.

Isolated berberine did not alter metformin pharmacokinetics in the mouse experiment, whereas goldenseal extract reduced metformin Cmax.

No clinically obvious pharmacokinetic interaction with simvastatin was detected in the tested berberine-chloride combination regimen.

No clinically obvious pharmacokinetic interaction with fenofibrate was detected in the tested berberine-chloride combination regimen.

Berberine displaced bilirubin from protein binding in vitro.

Repeated intraperitoneal berberine increased unbound bilirubin concentrations in adult rats.

Oral berberine increased microbial butyrate production in the animal and bacterial-culture experiments.

Berberine reduced bacterial ATP production in the tested gut bacterial systems.

Berberine reduced bacterial NADH levels in the tested systems.

The study reported increased bacterial phosphotransbutyrylase in the pathway associated with increased butyrate production.

The study reported increased bacterial butyrate kinase in the pathway associated with increased butyrate production.

The study reported increased bacterial butyryl-CoA:acetate-CoA transferase in the pathway associated with increased butyrate production.

Antibiotic pretreatment abolished the berberine-associated rise in butyrate.

Berberine lowered TMA/TMAO production in choline-fed mice; labeled-choline tracing supported altered microbial conversion.

Metagenomics identified altered cutC/cntA abundance alongside changes in microbial composition after berberine.