Berberine

evidence_access

Primary abstract

experimental_model

Human endothelial-cell experiments accompanying diabetic-rat study.

limitations

Pathway association does not establish direct inhibition of ERK or Akt by berberine at human exposure.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

Protection from one compound’s cellular toxicity can accompany lower signaling activity.

primary_references

Vanadyl Acetylacetonate and Berberine Synergistically Ameliorate Diabetes-induced Vascular Dysfunction and Reduce Endothelial Toxicity through ERK and Akt Regulation. · 2026 · https://pubmed.ncbi.nlm.nih.gov/40775562/ · DOI 10.1007/s12011-025-04774-z

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 350–356

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human endothelial-cell experiments accompanying diabetic-rat study. · source_derived_draft · unverified_draft

## vanadium-berberine-endothelium Protection from one compound’s cellular toxicity can accompany lower signaling activity. In HUVEC experiments, berberine reduced vanadyl-acetylacetonate-associated apoptosis, junction/cytoskeleton damage and permeability changes, with lower excessive ERK/Akt phosphorylation. Model: Human endothelial-cell experiments accompanying diabetic-rat study. Limitations: Pathway association does not establish direct inhibition of ERK or Akt by berberine at human exposure. Evidence access: Primary abstract Vanadyl Acetylacetonate and Berberine Synergistically Ameliorate Diabetes-induced Vascular Dysfunction and Reduce Endothelial Toxicity through ERK and Akt Regulation. · 2026 · https://pubmed.ncbi.nlm.nih.gov/40775562/ · DOI 10.1007/s12011-025-04774-z

evidence_access

Primary abstract

experimental_model

Diabetic rats; primary abstract accessed.

limitations

Preclinical formulation-specific findings; doses and formal synergy modeling are not resolved in accessed abstract. Not a recommendation to combine supplements.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

A specific tested combination is recorded rather than inferred from a shared pathway.

primary_references

Vanadyl Acetylacetonate and Berberine Synergistically Ameliorate Diabetes-induced Vascular Dysfunction and Reduce Endothelial Toxicity through ERK and Akt Regulation. · 2026 · https://pubmed.ncbi.nlm.nih.gov/40775562/ · DOI 10.1007/s12011-025-04774-z

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 342–348

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Diabetic rats; primary abstract accessed. · source_derived_draft · unverified_draft

## vanadium-berberine-vascular-combination A specific tested combination is recorded rather than inferred from a shared pathway. The rat study reported that berberine plus vanadyl acetylacetonate reduced hyperglycemia and improved vascular calcification, junction and barrier outcomes compared with single-agent conditions. Model: Diabetic rats; primary abstract accessed. Limitations: Preclinical formulation-specific findings; doses and formal synergy modeling are not resolved in accessed abstract. Not a recommendation to combine supplements. Evidence access: Primary abstract Vanadyl Acetylacetonate and Berberine Synergistically Ameliorate Diabetes-induced Vascular Dysfunction and Reduce Endothelial Toxicity through ERK and Akt Regulation. · 2026 · https://pubmed.ncbi.nlm.nih.gov/40775562/ · DOI 10.1007/s12011-025-04774-z

evidence_span

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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

evidence_span

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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

evidence_span

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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

evidence_span

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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

evidence_span

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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

evidence_span

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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

evidence_span

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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

evidence_span

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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

evidence_span

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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