Human P-glycoprotein / ABCB1 / MDR1

evidence_span

{"source_cache": "artifacts/sulforaphane-research/11988104.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5759bc0af52a1e906602549a3920ebba5641d09b63cc87f0dc61ea8efcb724a9", "start_char": 0, "end_char": 1567, "text_sha256": "5759bc0af52a1e906602549a3920ebba5641d09b63cc87f0dc61ea8efcb724a9"}

experimental_model

Transporter-overexpression and temperature/inhibitor experiments

exposure

Sulforaphane loading; ABCC1 or ABCB1 expression

limitations

Cancer-cell transport experiments; not a measured clinical drug interaction.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human HL60 leukemia and 8226 myeloma cells

plain_language

The measured pool can be influenced by more than one transporter.

primary_references

[sulforaphane-p11988104] High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. (2002). https://pubmed.ncbi.nlm.nih.gov/11988104/ DOI: 10.1042/bj3640301

tissue_or_cell_type

Intracellular retention and export

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 320–331

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-overexpression and temperature/inhibitor experiments · source_derived_draft · unverified_draft

### sulforaphane-abcb1-efflux P-glycoprotein overexpression also implicated ABCB1 in export of intracellular sulforaphane/conjugate pools. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured pool can be influenced by more than one transporter. organism: Human HL60 leukemia and 8226 myeloma cells tissue_or_cell_type: Intracellular retention and export experimental_model: Transporter-overexpression and temperature/inhibitor experiments limitations: Cancer-cell transport experiments; not a measured clinical drug interaction. exposure: Sulforaphane loading; ABCC1 or ABCB1 expression evidence_span: {"source_cache": "artifacts/sulforaphane-research/11988104.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5759bc0af52a1e906602549a3920ebba5641d09b63cc87f0dc61ea8efcb724a9", "start_char": 0, "end_char": 1567, "text_sha256": "5759bc0af52a1e906602549a3920ebba5641d09b63cc87f0dc61ea8efcb724a9"} [sulforaphane-p11988104] High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. (2002). https://pubmed.ncbi.nlm.nih.gov/11988104/ DOI: 10.1042/bj3640301

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

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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

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

mdr1a homozygous knockout mice compared with wild type

exposure

Ivermectin, described in this report as a centrally neurotoxic pesticide

limitations

The comparison is a complete gene disruption, which is a stronger manipulation than partial pharmacological inhibition of P-glycoprotein.

organism

mdr1a homozygous knockout mice compared with wild type

plain_language

Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier.

primary_references

Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. (1994). https://pubmed.ncbi.nlm.nih.gov/7910522/ DOI: 10.1016/0092-8674(94)90212-7

route

In vivo

tissue

Blood-brain barrier and tissue drug distribution

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 57–66

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## pgp-restricts-ivermectin-brain-entry Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier. Model/species: mdr1a homozygous knockout mice compared with wild type Tissue/system: Blood-brain barrier and tissue drug distribution Exposure: Ivermectin, described in this report as a centrally neurotoxic pesticide Route: In vivo Duration: Not stated here Limits: The comparison is a complete gene disruption, which is a stronger manipulation than partial pharmacological inhibition of P-glycoprotein. Primary reference: Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. (1994). https://pubmed.ncbi.nlm.nih.gov/7910522/ DOI: 10.1016/0092-8674(94)90212-7 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_span

{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}

experimental_model

Promoter reporters, expression, knockdown and transport assays

exposure

DIM exposure with PXR inhibition or knockdown controls

limitations

Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human hepatocytes and intestinal cell models

plain_language

The same exposure can change a transporter as well as an enzyme.

primary_references

[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

tissue_or_cell_type

PXR-regulated CYP3A4 and ABCB1

Diindolylmethane (DIM): formation, receptor signaling, metabolism 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 · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft

### dim-pxr-abcb1 DIM increased MDR1/ABCB1 expression in a PXR-dependent manner. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same exposure can change a transporter as well as an enzyme. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}

experimental_model

Promoter reporters, expression, knockdown and transport assays

exposure

DIM exposure with PXR inhibition or knockdown controls

limitations

Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human hepatocytes and intestinal cell models

plain_language

The response weakened when a required signaling component was blocked.

primary_references

[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

tissue_or_cell_type

PXR-regulated CYP3A4 and ABCB1

trigger_kind

machinery_impairment Imported condition classification; unverified.

Diindolylmethane (DIM): formation, receptor signaling, metabolism 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 · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft

### dim-pxr-loss-abcb1 PXR knockdown or inhibition attenuated DIM-induced ABCB1 expression. Condition category: machinery_impairment nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response weakened when a required signaling component was blocked. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

evidence_access

Primary full text PMC3513969

experimental_model

Canine MDCK cells engineered with human MDR1; radiolabeled digoxin probe.

limitations

Human transporter in a canine host cell; not a clinical digoxin-interaction magnitude.

nutrient_topic

Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice

plain_language

An efflux transporter provides another exposure-related route.

primary_references

[23227093] Interaction between Red Yeast Rice and CYP450 Enzymes/P-Glycoprotein and Its Implication for the Clinical Pharmacokinetics of Lovastatin. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23227093/ · DOI 10.1155/2012/127043

Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 132–138

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Canine MDCK cells engineered with human MDR1; radiolabeled digoxin probe. · source_derived_draft · unverified_draft

## red-yeast-rice-extract-pgp An efflux transporter provides another exposure-related route. The three product extracts inhibited P-glycoprotein transport activity more potently than pure lovastatin in the study assay. Model: Canine MDCK cells engineered with human MDR1; radiolabeled digoxin probe. Limitations: Human transporter in a canine host cell; not a clinical digoxin-interaction magnitude. Evidence access: Primary full text PMC3513969 [23227093] Interaction between Red Yeast Rice and CYP450 Enzymes/P-Glycoprotein and Its Implication for the Clinical Pharmacokinetics of Lovastatin. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23227093/ · DOI 10.1155/2012/127043

evidence_span

{"source_cache": "artifacts/berberine-research/29891588.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405", "start_char": 0, "end_char": 1752, "text_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405"}

experimental_model

Nrf2 reporter, gene silencing and expression assays

exposure

Berberine concentration and time response

limitations

Transporter expression after prolonged exposure is not the same endpoint as acute competitive inhibition. Rat colitis improvement does not establish human IBD efficacy.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Human Caco-2 cells; rat colitis in a separate arm

plain_language

Repeated exposure can increase the pump that exports drugs.

primary_references

[berberine-p29891588] Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms. (2018). https://pubmed.ncbi.nlm.nih.gov/29891588/ DOI: 10.1124/jpet.118.249615

tissue_or_cell_type

Nrf2-dependent ABCB1 expression

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 545–556

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nrf2 reporter, gene silencing and expression assays · source_derived_draft · unverified_draft

### berberine-abcb1-expression Berberine increased MDR1/ABCB1 expression; Nrf2 silencing abolished the gene response in Caco-2 cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Repeated exposure can increase the pump that exports drugs. organism: Human Caco-2 cells; rat colitis in a separate arm tissue_or_cell_type: Nrf2-dependent ABCB1 expression experimental_model: Nrf2 reporter, gene silencing and expression assays limitations: Transporter expression after prolonged exposure is not the same endpoint as acute competitive inhibition. Rat colitis improvement does not establish human IBD efficacy. exposure: Berberine concentration and time response evidence_span: {"source_cache": "artifacts/berberine-research/29891588.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405", "start_char": 0, "end_char": 1752, "text_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405"} [berberine-p29891588] Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms. (2018). https://pubmed.ncbi.nlm.nih.gov/29891588/ DOI: 10.1124/jpet.118.249615

dose

Tartrazine 0.1-1000 micromolar, rhodamine-123 5 micromolar; GF120918 positive control

duration

1 h at 37 C

evidence_access

Primary full-text methods/results and metadata.

evidence_scope

literature_reviewed; source-specific experimental curation

experimental_model

LLC-MDR1-WT cells expressing recombinant human ABCB1

limitations

Human transporter in a heterologous cell system. Negative P-gp inhibition is not inconsistent with a BCRP effect in a different assay.

nutrient_topic

Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine

organism

LLC-MDR1-WT cells expressing recombinant human ABCB1

plain_language

Tartrazine did not inhibit human P-glycoprotein-mediated rhodamine-123 efflux in the cell assay.

primary_references

Food dyes as P-glycoprotein modulators. (2020). https://pubmed.ncbi.nlm.nih.gov/33011351/ DOI: 10.1016/j.fct.2020.111785

route

In vitro co-incubation

tissue

Rhodamine-123 efflux assay

Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 237–246

Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · LLC-MDR1-WT cells expressing recombinant human ABCB1 · source_derived_draft · unverified_draft

## tartrazine-pgp-efflux-null Tartrazine did not inhibit human P-glycoprotein-mediated rhodamine-123 efflux in the cell assay. Model/species: LLC-MDR1-WT cells expressing recombinant human ABCB1 Tissue: Rhodamine-123 efflux assay Exposure: Tartrazine 0.1-1000 micromolar, rhodamine-123 5 micromolar; GF120918 positive control Route: In vitro co-incubation Duration: 1 h at 37 C Limits: Human transporter in a heterologous cell system. Negative P-gp inhibition is not inconsistent with a BCRP effect in a different assay. Primary reference: Food dyes as P-glycoprotein modulators. (2020). https://pubmed.ncbi.nlm.nih.gov/33011351/ DOI: 10.1016/j.fct.2020.111785 Access: Primary full-text methods/results and metadata.

evidence_access

Primary abstract

experimental_model

Drug-resistant human breast-cell model.

limitations

Functional probe result, not proof of selective direct binding or human intestinal inhibition.

nutrient_topic

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

plain_language

Less export can increase intracellular probe retention.

primary_references

Effects of myricetin on the bioavailability of carvedilol in rats. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22132944/ · DOI 10.3109/13880209.2011.611141

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 236–242

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Drug-resistant human breast-cell model. · source_derived_draft · unverified_draft

## myricetin-pgp-efflux Less export can increase intracellular probe retention. Myricetin increased rhodamine-123 accumulation in P-glycoprotein-overexpressing human MCF-7/ADR cells. Model: Drug-resistant human breast-cell model. Limitations: Functional probe result, not proof of selective direct binding or human intestinal inhibition. Evidence access: Primary abstract Effects of myricetin on the bioavailability of carvedilol in rats. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22132944/ · DOI 10.3109/13880209.2011.611141

evidence_span

{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}

experimental_model

Promoter reporters, expression, knockdown and transport assays

exposure

DIM exposure with PXR inhibition or knockdown controls

limitations

Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human hepatocytes and intestinal cell models

plain_language

A tracer supported increased efflux; it did not measure every drug.

primary_references

[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

tissue_or_cell_type

PXR-regulated CYP3A4 and ABCB1

Diindolylmethane (DIM): formation, receptor signaling, metabolism 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 · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft

### dim-abcb1-efflux DIM reduced intracellular accumulation of the MDR1 substrate rhodamine 123 in the transport experiment. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A tracer supported increased efflux; it did not measure every drug. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

evidence_access

Primary full text PMC3513969

experimental_model

Human intestinal-cell-line model.

limitations

Does not quantify intestinal absorption or oral bioavailability in humans.

nutrient_topic

Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice

plain_language

A cell-layer transport result supported a mixture effect.

primary_references

[23227093] Interaction between Red Yeast Rice and CYP450 Enzymes/P-Glycoprotein and Its Implication for the Clinical Pharmacokinetics of Lovastatin. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23227093/ · DOI 10.1155/2012/127043

Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 140–146

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human intestinal-cell-line model. · source_derived_draft · unverified_draft

## red-yeast-rice-extract-caco2-flux A cell-layer transport result supported a mixture effect. Lovastatin flux across Caco-2 monolayers was higher with the three product extracts than with pure lovastatin at a matched 25 micromolar concentration. Model: Human intestinal-cell-line model. Limitations: Does not quantify intestinal absorption or oral bioavailability in humans. Evidence access: Primary full text PMC3513969 [23227093] Interaction between Red Yeast Rice and CYP450 Enzymes/P-Glycoprotein and Its Implication for the Clinical Pharmacokinetics of Lovastatin. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23227093/ · DOI 10.1155/2012/127043

dose

Tartrazine 0.41-900 micromolar; verapamil and orthovanadate controls

duration

Manufacturer ATPase assay interval not stated in accessed methods

evidence_access

Primary full-text methods/results and metadata.

evidence_scope

literature_reviewed; source-specific experimental curation

experimental_model

Recombinant human P-glycoprotein in membrane preparations

limitations

A negative ATPase-stimulation result is bounded by the assay and does not establish universal lack of transport interactions.

nutrient_topic

Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine

organism

Recombinant human P-glycoprotein in membrane preparations

plain_language

Tartrazine did not stimulate P-glycoprotein-specific ATPase activity in the membrane assay.

primary_references

Food dyes as P-glycoprotein modulators. (2020). https://pubmed.ncbi.nlm.nih.gov/33011351/ DOI: 10.1016/j.fct.2020.111785

route

In vitro membrane assay

tissue

ATPase stimulation assay

Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 226–235

Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Recombinant human P-glycoprotein in membrane preparations · source_derived_draft · unverified_draft

## tartrazine-pgp-atpase-null Tartrazine did not stimulate P-glycoprotein-specific ATPase activity in the membrane assay. Model/species: Recombinant human P-glycoprotein in membrane preparations Tissue: ATPase stimulation assay Exposure: Tartrazine 0.41-900 micromolar; verapamil and orthovanadate controls Route: In vitro membrane assay Duration: Manufacturer ATPase assay interval not stated in accessed methods Limits: A negative ATPase-stimulation result is bounded by the assay and does not establish universal lack of transport interactions. Primary reference: Food dyes as P-glycoprotein modulators. (2020). https://pubmed.ncbi.nlm.nih.gov/33011351/ DOI: 10.1016/j.fct.2020.111785 Access: Primary full-text methods/results and metadata.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

mdr1a,b double knockout mice and bcrp knockout mice, against wild type

exposure

Ivermectin 0.2 mg/kg and selamectin 12 mg/kg, intravenous, oral and dermal spot-on

limitations

Breast cancer resistance protein knockouts showed no difference, so this margin is specific to P-glycoprotein and not to efflux transport in general.

organism

mdr1a,b double knockout mice and bcrp knockout mice, against wild type

plain_language

Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold.

primary_references

Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19161460/ DOI: 10.1111/j.1365-2885.2008.01007.x

route

In vivo

tissue

Brain penetration, organ distribution and plasma kinetics

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 68–77

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-brain-accumulation-without-pgp Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold. Model/species: mdr1a,b double knockout mice and bcrp knockout mice, against wild type Tissue/system: Brain penetration, organ distribution and plasma kinetics Exposure: Ivermectin 0.2 mg/kg and selamectin 12 mg/kg, intravenous, oral and dermal spot-on Route: In vivo Duration: Not stated here Limits: Breast cancer resistance protein knockouts showed no difference, so this margin is specific to P-glycoprotein and not to efflux transport in general. Primary reference: Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19161460/ DOI: 10.1111/j.1365-2885.2008.01007.x Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/mebendazole-research/25862759.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7545a89b4d17461bbe2d8ac8c7f3093b6ae0ce2f20307ab57b524d91f4f827c3", "start_char": 0, "end_char": 1682, "text_sha256": "7545a89b4d17461bbe2d8ac8c7f3093b6ae0ce2f20307ab57b524d91f4f827c3"}

experimental_model

Polymorph content of marketed and custom tablets measured by infrared spectroscopy, then tested in orthotopic mouse glioma and medulloblastoma models with LC/MS pharmacokinetics

exposure

Polymorphs A, B and C, alone and with the transporter inhibitor elacridar

limitations

Carries the polymorph distinction across from the anthelmintic use into the oncology use and finds it decides brain exposure. Mouse models, and elacridar is an experimental tool rather than a co-therapy.

nutrient_topic

Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. · Mebendazole

organism

Mouse

plain_language

The same crystal form that works against worms is the one that gets into the brain; the inert form stays out of the blood entirely.

primary_references

[mbz-p25862759] Brain Penetration and Efficacy of Different Mebendazole Polymorphs in a Mouse Brain Tumor Model. (2015). https://pubmed.ncbi.nlm.nih.gov/25862759/ DOI: 10.1158/1078-0432.ccr-14-2681

tissue_or_cell_type

Brain and plasma

trigger_kind

biomarker_context Imported condition classification; unverified.

Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 524–535

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polymorph content of marketed and custom tablets measured by infrared spectroscopy, then tested in orthotopic mouse glioma and medulloblastoma models with LC/MS pharmacokinetics · source_derived_draft · unverified_draft

### mbz-polymorph-decides-brain-levels Polymorph B and polymorph C both increased survival in a GL261 glioma model with B exhibiting greater toxicity, polymorph A showed no benefit, B and C both reached brain concentrations exceeding the GL261 half-maximal inhibitory concentration 29-fold, polymorph C demonstrated a 24-hour brain-to-plasma area-under-curve ratio of 0.82 while B showed higher plasma exposure and a lower ratio, polymorph A presented markedly lower levels in both plasma and brain, and combination with elacridar significantly improved the efficacy of polymorph C in glioma and medulloblastoma models. Condition category: biomarker_context nutrient_topic: Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. plain_language: The same crystal form that works against worms is the one that gets into the brain; the inert form stays out of the blood entirely. organism: Mouse tissue_or_cell_type: Brain and plasma experimental_model: Polymorph content of marketed and custom tablets measured by infrared spectroscopy, then tested in orthotopic mouse glioma and medulloblastoma models with LC/MS pharmacokinetics limitations: Carries the polymorph distinction across from the anthelmintic use into the oncology use and finds it decides brain exposure. Mouse models, and elacridar is an experimental tool rather than a co-therapy. exposure: Polymorphs A, B and C, alone and with the transporter inhibitor elacridar evidence_span: {"source_cache": "artifacts/mebendazole-research/25862759.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7545a89b4d17461bbe2d8ac8c7f3093b6ae0ce2f20307ab57b524d91f4f827c3", "start_char": 0, "end_char": 1682, "text_sha256": "7545a89b4d17461bbe2d8ac8c7f3093b6ae0ce2f20307ab57b524d91f4f827c3"} [mbz-p25862759] Brain Penetration and Efficacy of Different Mebendazole Polymorphs in a Mouse Brain Tumor Model. (2015). https://pubmed.ncbi.nlm.nih.gov/25862759/ DOI: 10.1158/1078-0432.ccr-14-2681