Human cytochrome P450 3A4

evidence_span

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experimental_model

Recombinant enzymes, antibodies and human liver microsomes

exposure

Enzyme-specific inhibition and metabolite formation

limitations

Identifies metabolic routes, not a trial of DIM with clozapine. Do not infer a dose change or magnitude of interaction.

nutrient_topic

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

organism

Human CYP enzymes

plain_language

Clozapine has more than one relevant route.

primary_references

[dim-p9384460] The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. (1997). https://pubmed.ncbi.nlm.nih.gov/9384460/ DOI: 10.1046/j.1365-2125.1997.t01-1-00605.x

tissue_or_cell_type

Clozapine oxidation

Diindolylmethane (DIM): formation, receptor signaling, metabolism 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 · Recombinant enzymes, antibodies and human liver microsomes · source_derived_draft · unverified_draft

### dim-clozapine-3a4 CYP3A4 contributed to clozapine demethylation and N-oxidation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Clozapine has more than one relevant route. organism: Human CYP enzymes tissue_or_cell_type: Clozapine oxidation experimental_model: Recombinant enzymes, antibodies and human liver microsomes limitations: Identifies metabolic routes, not a trial of DIM with clozapine. Do not infer a dose change or magnitude of interaction. exposure: Enzyme-specific inhibition and metabolite formation evidence_span: {"source_cache": "artifacts/dim-research/9384460.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6", "start_char": 0, "end_char": 1794, "text_sha256": "eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6"} [dim-p9384460] The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. (1997). https://pubmed.ncbi.nlm.nih.gov/9384460/ DOI: 10.1046/j.1365-2125.1997.t01-1-00605.x

evidence_span

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experimental_model

Microsomal metabolism and drug-interaction prediction

exposure

CYP1A2, CYP2C19 and CYP3A4 assays

limitations

In-vitro estimated shares vary by pathway and model. Fluvoxamine inhibits multiple routes; its large interaction cannot be inverted into a DIM prediction.

nutrient_topic

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

organism

Human liver and intestinal microsomes

plain_language

Ramelteon has several metabolic routes; none here measures a DIM interaction.

primary_references

[dim-p20478852] Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. (2010). https://pubmed.ncbi.nlm.nih.gov/20478852/ DOI: 10.1124/dmd.110.034009

tissue_or_cell_type

Ramelteon metabolism

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 896–907

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal metabolism and drug-interaction prediction · source_derived_draft · unverified_draft

### dim-ramelteon-cyp3a4 CYP3A4 catalyzed ramelteon metabolism in the tested microsomal/recombinant system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ramelteon has several metabolic routes; none here measures a DIM interaction. organism: Human liver and intestinal microsomes tissue_or_cell_type: Ramelteon metabolism experimental_model: Microsomal metabolism and drug-interaction prediction limitations: In-vitro estimated shares vary by pathway and model. Fluvoxamine inhibits multiple routes; its large interaction cannot be inverted into a DIM prediction. exposure: CYP1A2, CYP2C19 and CYP3A4 assays evidence_span: {"source_cache": "artifacts/dim-research/20478852.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e", "start_char": 0, "end_char": 1696, "text_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e"} [dim-p20478852] Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. (2010). https://pubmed.ncbi.nlm.nih.gov/20478852/ DOI: 10.1124/dmd.110.034009

evidence_span

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experimental_model

Kinetic, inhibition and recombinant-enzyme pathway mapping

exposure

Therapeutically relevant substrate concentrations

limitations

Biochemical pathway identity; does not attribute the observed DIM interaction to any single CYP or prove clinical cancer outcomes.

nutrient_topic

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

organism

Human liver microsomes and expressed CYPs

plain_language

The route to active metabolites begins with several linked transformations.

primary_references

[dim-p15159443] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. (2004). https://pubmed.ncbi.nlm.nih.gov/15159443/ DOI: 10.1124/jpet.104.065607

tissue_or_cell_type

Sequential tamoxifen metabolism

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 987–998

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetic, inhibition and recombinant-enzyme pathway mapping · source_derived_draft · unverified_draft

### dim-tamoxifen-3a4 CYP3A4/5 catalyzed formation of N-desmethyltamoxifen, the quantitatively major initial pathway. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The route to active metabolites begins with several linked transformations. organism: Human liver microsomes and expressed CYPs tissue_or_cell_type: Sequential tamoxifen metabolism experimental_model: Kinetic, inhibition and recombinant-enzyme pathway mapping limitations: Biochemical pathway identity; does not attribute the observed DIM interaction to any single CYP or prove clinical cancer outcomes. exposure: Therapeutically relevant substrate concentrations evidence_span: {"source_cache": "artifacts/dim-research/15159443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081", "start_char": 0, "end_char": 1544, "text_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081"} [dim-p15159443] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. (2004). https://pubmed.ncbi.nlm.nih.gov/15159443/ DOI: 10.1124/jpet.104.065607

duration

Not stated here

evidence_access

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

experimental_model

Heterologously expressed human CYP3A4

exposure

Cyclosporin A

limitations

Substrate inhibition means the rate does not rise linearly with concentration, so a single-point rate from this system does not scale. The step consumes the parent drug, which is the direction recorded.

organism

Heterologously expressed human CYP3A4

plain_language

Heterologously expressed CYP3A4 produced three primary cyclosporine metabolites, AM1, AM9 and AM4N, with substrate inhibition observed for AM1 and AM9 formation.

primary_references

In vitro metabolism of cyclosporine A by human kidney CYP3A5. (2004). https://pubmed.ncbi.nlm.nih.gov/15450954/ DOI: 10.1016/j.bcp.2004.07.012

route

In vitro

tissue

Oxidative drug metabolism

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 179–179

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Heterologously expressed human CYP3A4 · source_derived_draft · unverified_draft

Heterologously expressed CYP3A4 produced three primary cyclosporine metabolites, AM1, AM9 and AM4N, with substrate inhibition observed for AM1 and AM9 formation.

evidence_access

Primary abstract

experimental_model

Human CYP expression and liver microsomes.

limitations

Not evidence that the two oral products give equivalent exposures.

nutrient_topic

Luteolin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Luteolin / 3′,4′,5,7-tetrahydroxyflavone

plain_language

A related flavone can be converted into luteolin.

primary_references

In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11955666/ · DOI 10.1016/s0278-6915(01)00125-9

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 148–154

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human CYP expression and liver microsomes. · source_derived_draft · unverified_draft

## luteolin-cyp3a4-apigenin A related flavone can be converted into luteolin. Recombinant human CYP3A4 supported apigenin 3′-hydroxylation to luteolin. Model: Human CYP expression and liver microsomes. Limitations: Not evidence that the two oral products give equivalent exposures. Evidence access: Primary abstract In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11955666/ · DOI 10.1016/s0278-6915(01)00125-9

evidence_access

Primary abstract

experimental_model

Recombinant human CYP comparison.

limitations

Explains a candidate source of urinary bias; not proof of drug induction.

nutrient_topic

Luteolin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Luteolin / 3′,4′,5,7-tetrahydroxyflavone

plain_language

Downstream removal can reverse the apparent product preference.

primary_references

Luteolin is a rare substrate of human catechol-O-methyltransferase favoring a para-methylation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23386290/ · DOI 10.1002/mnfr.201200584

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 108–114

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human CYP comparison. · source_derived_draft · unverified_draft

## luteolin-cyp3a4-demethylation Downstream removal can reverse the apparent product preference. Human CYP3A4 demethylated diosmetin more readily than chrysoeriol in vitro. Model: Recombinant human CYP comparison. Limitations: Explains a candidate source of urinary bias; not proof of drug induction. Evidence access: Primary abstract Luteolin is a rare substrate of human catechol-O-methyltransferase favoring a para-methylation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23386290/ · DOI 10.1002/mnfr.201200584

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

In vitro biotransformation in human liver microsomes and microsomes containing heterologously expressed cytochromes

exposure

Formation of the major circulating metabolite with chemical inhibitors and cDNA-expressed cytochromes

limitations

Assigns the clearance quantitatively across cytochromes and identifies the inhibitors that matter. In vitro microsomes.

nutrient_topic

Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil

organism

Human

plain_language

Four fifths of the clearance runs through one enzyme, so anything blocking that enzyme raises the level of the drug.

primary_references

[sil-p10725306] In vitro biotransformation of sildenafil (Viagra): identification of human cytochromes and potential drug interactions. (2000). https://pubmed.ncbi.nlm.nih.gov/10725306/ DOI: 10.1016/s0090-9556(24)15055-6

tissue_or_cell_type

Liver microsomes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 457–468

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vitro biotransformation in human liver microsomes and microsomes containing heterologously expressed cytochromes · source_derived_draft · unverified_draft

### sil-cyp3a4-carries-the-clearance Formation of the major circulating metabolite in human liver microsomes had a Michaelis constant of 14.4 micromolar, of the chemical inhibitors screened only ketoconazole showed detectable inhibition, biotransformation was inhibited by ketoconazole and ritonavir with half-maximal concentrations below 0.02 micromolar, and using microsomes containing cDNA-expressed cytochromes the reaction was mediated by CYP3A4, CYP2C9, CYP2C19 and CYP2D6 with estimated relative contributions to net intrinsic clearance of 79% for CYP3A4 and 20% for CYP2C9 and less than 2% for the other two. Condition category: machinery_impairment nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: Four fifths of the clearance runs through one enzyme, so anything blocking that enzyme raises the level of the drug. organism: Human tissue_or_cell_type: Liver microsomes experimental_model: In vitro biotransformation in human liver microsomes and microsomes containing heterologously expressed cytochromes limitations: Assigns the clearance quantitatively across cytochromes and identifies the inhibitors that matter. In vitro microsomes. exposure: Formation of the major circulating metabolite with chemical inhibitors and cDNA-expressed cytochromes evidence_span: {"source_cache": "artifacts/sildenafil-research/10725306.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21d73da8afc20cb90f2aa2d9bafe7bdbefd7d07037ffb493681414b09154f6d6", "start_char": 0, "end_char": 1190, "text_sha256": "21d73da8afc20cb90f2aa2d9bafe7bdbefd7d07037ffb493681414b09154f6d6"} [sil-p10725306] In vitro biotransformation of sildenafil (Viagra): identification of human cytochromes and potential drug interactions. (2000). https://pubmed.ncbi.nlm.nih.gov/10725306/ DOI: 10.1016/s0090-9556(24)15055-6

evidence_access

Primary abstract

experimental_model

Human liver microsomes with ketoconazole and bromocriptine.

limitations

Enzyme attribution was pharmacological, not a single-enzyme knockout.

nutrient_topic

Caffeine collection; salts, coffee, species and coexposure contexts retain their identities. · Caffeine

plain_language

A minor oxidative branch differs from demethylation.

primary_references

Fluvoxamine is a potent inhibitor of the metabolism of caffeine in vitro. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9868741/ · DOI 10.1111/j.1600-0773.1998.tb01476.x

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 220–226

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human liver microsomes with ketoconazole and bromocriptine. · source_derived_draft · unverified_draft

## caf-cyp3a4 A minor oxidative branch differs from demethylation. Inhibitor experiments supported CYP3A4 involvement in caffeine 8-hydroxylation to trimethyluric acid. Model: Human liver microsomes with ketoconazole and bromocriptine. Limitations: Enzyme attribution was pharmacological, not a single-enzyme knockout. Evidence access: Primary abstract Fluvoxamine is a potent inhibitor of the metabolism of caffeine in vitro. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9868741/ · DOI 10.1111/j.1600-0773.1998.tb01476.x

dose

Isolated constituents up to the assay range

duration

Acute

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Recombinant or assay-system human CYP3A4/CYP2D6 panel

limitations

Bioavailability was unresolved, so these concentrations cannot be treated as expected human exposure or used to predict a specific medicine interaction.

nutrient_topic

Moringa oleifera chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Moringa oleifera

organism

Recombinant or assay-system human CYP3A4/CYP2D6 panel

plain_language

Several isolated Moringa leaf metabolites inhibited CYP3A4 at 41.5-100 micromolar but showed no remarkable CYP2D6 inhibition in the same in-vitro panel.

primary_references

Isolation, synthesis, and drug interaction potential of secondary metabolites derived from the leaves of miracle tree (Moringa oleifera) against CYP3A4 and CYP2D6 isozymes. (2019). https://pubmed.ncbi.nlm.nih.gov/31301970/ DOI: 10.1016/j.phymed.2019.153010

route

In vitro

tissue

CYP isozyme inhibition

Moringa oleifera: mechanism of action and interactions (2026-09-20) · lines 211–220

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Recombinant or assay-system human CYP3A4/CYP2D6 panel · source_derived_draft · unverified_draft

## moringa-isolated-constituent-cyp-selectivity Several isolated Moringa leaf metabolites inhibited CYP3A4 at 41.5-100 micromolar but showed no remarkable CYP2D6 inhibition in the same in-vitro panel. Model/species: Recombinant or assay-system human CYP3A4/CYP2D6 panel Tissue/system: CYP isozyme inhibition Exposure: Isolated constituents up to the assay range Route: In vitro Duration: Acute Limits: Bioavailability was unresolved, so these concentrations cannot be treated as expected human exposure or used to predict a specific medicine interaction. Primary reference: Isolation, synthesis, and drug interaction potential of secondary metabolites derived from the leaves of miracle tree (Moringa oleifera) against CYP3A4 and CYP2D6 isozymes. (2019). https://pubmed.ncbi.nlm.nih.gov/31301970/ DOI: 10.1016/j.phymed.2019.153010 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_span

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experimental_model

Pretreatment versus cotreatment, adduct and recombinant-enzyme assays

exposure

DIM pretreatment for 48 hours; direct catalytic assays separately

limitations

Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs.

nutrient_topic

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

organism

Primary human hepatocytes and human enzyme preparations

plain_language

Direct enzyme inhibition can oppose a slower increase in enzyme production.

primary_references

[dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206

tissue_or_cell_type

Aflatoxin metabolism and CYP catalytic activity

Diindolylmethane (DIM): formation, receptor signaling, metabolism 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 · Pretreatment versus cotreatment, adduct and recombinant-enzyme assays · source_derived_draft · unverified_draft

### dim-cyp3a4-direct-inhibition DIM directly inhibited CYP3A4 catalytic activity in the tested enzyme assay. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Direct enzyme inhibition can oppose a slower increase in enzyme production. organism: Primary human hepatocytes and human enzyme preparations tissue_or_cell_type: Aflatoxin metabolism and CYP catalytic activity experimental_model: Pretreatment versus cotreatment, adduct and recombinant-enzyme assays limitations: Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs. exposure: DIM pretreatment for 48 hours; direct catalytic assays separately evidence_span: {"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"} [dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206

evidence_span

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experimental_model

Precision-cut liver-slice induction and immunoblotting

exposure

DIM 50 micromolar for 72 hours

limitations

Ex-vivo exposure; not a measured oral DIM effect on a patient drug concentration. Four donors showed variable responses.

nutrient_topic

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

organism

Human donor liver slices

plain_language

A result for one CYP family cannot simply be assigned to another.

primary_references

[dim-p9741959] 3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. (1998). https://pubmed.ncbi.nlm.nih.gov/9741959/ DOI: 10.1080/004982598239227

tissue_or_cell_type

CYP1A proteins and catalytic assays

Diindolylmethane (DIM): formation, receptor signaling, metabolism 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 · Precision-cut liver-slice induction and immunoblotting · source_derived_draft · unverified_draft

### dim-liver-cyp3a4-null The same liver-slice experiment found little effect of DIM on CYP3A4 protein. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A result for one CYP family cannot simply be assigned to another. organism: Human donor liver slices tissue_or_cell_type: CYP1A proteins and catalytic assays experimental_model: Precision-cut liver-slice induction and immunoblotting limitations: Ex-vivo exposure; not a measured oral DIM effect on a patient drug concentration. Four donors showed variable responses. exposure: DIM 50 micromolar for 72 hours evidence_span: {"source_cache": "artifacts/dim-research/9741959.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11eec60fad1ec0e18085a59f90fa3237235bb0614b5ee2b29058757e3b45ba47", "start_char": 0, "end_char": 1338, "text_sha256": "11eec60fad1ec0e18085a59f90fa3237235bb0614b5ee2b29058757e3b45ba47"} [dim-p9741959] 3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. (1998). https://pubmed.ncbi.nlm.nih.gov/9741959/ DOI: 10.1080/004982598239227

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

CYP3A4 belongs in this map alongside CYP1A2.

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 506–517

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-cyp3a4 DIM increased CYP3A4 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: CYP3A4 belongs in this map alongside CYP1A2. 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 545–556

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-cyp3a4 PXR knockdown or inhibition attenuated DIM-induced CYP3A4 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_span

{"source_cache": "artifacts/sulforaphane-research/20442190.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "130e0a3ab9cbabd496a64344ae8bfb9f98cccbf7521a64ec807f14b2259ceb69", "start_char": 0, "end_char": 1705, "text_sha256": "130e0a3ab9cbabd496a64344ae8bfb9f98cccbf7521a64ec807f14b2259ceb69"}

experimental_model

Primary human hepatocyte pretreatment and genotyping

exposure

Sulforaphane 10 or 50 micromolar for 48 hours before aflatoxin B1

limitations

Culture exposures are not ordinary plasma exposures; reduced CYP3A4 mRNA does not establish the direction of clinical drug interactions.

nutrient_topic

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

organism

Human hepatocyte cultures

plain_language

Suppressed activation machinery, rather than increased GST expression, accompanied the response.

primary_references

[sulforaphane-p20442190] Sulforaphane- and phenethyl isothiocyanate-induced inhibition of aflatoxin B1-mediated genotoxicity in human hepatocytes: role of GSTM1 genotype and CYP3A4 gene expression. (2010). https://pubmed.ncbi.nlm.nih.gov/20442190/ DOI: 10.1093/toxsci/kfq135

tissue_or_cell_type

Aflatoxin activation and DNA damage

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1230–1241

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human hepatocyte pretreatment and genotyping · source_derived_draft · unverified_draft

### sulforaphane-cyp3a4-transcription Sulforaphane strongly reduced CYP3A4 mRNA in primary human hepatocytes without inducing GSTM1 or GSTT1 expression. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Suppressed activation machinery, rather than increased GST expression, accompanied the response. organism: Human hepatocyte cultures tissue_or_cell_type: Aflatoxin activation and DNA damage experimental_model: Primary human hepatocyte pretreatment and genotyping limitations: Culture exposures are not ordinary plasma exposures; reduced CYP3A4 mRNA does not establish the direction of clinical drug interactions. exposure: Sulforaphane 10 or 50 micromolar for 48 hours before aflatoxin B1 evidence_span: {"source_cache": "artifacts/sulforaphane-research/20442190.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "130e0a3ab9cbabd496a64344ae8bfb9f98cccbf7521a64ec807f14b2259ceb69", "start_char": 0, "end_char": 1705, "text_sha256": "130e0a3ab9cbabd496a64344ae8bfb9f98cccbf7521a64ec807f14b2259ceb69"} [sulforaphane-p20442190] Sulforaphane- and phenethyl isothiocyanate-induced inhibition of aflatoxin B1-mediated genotoxicity in human hepatocytes: role of GSTM1 genotype and CYP3A4 gene expression. (2010). https://pubmed.ncbi.nlm.nih.gov/20442190/ DOI: 10.1093/toxsci/kfq135

evidence_span

{"source_cache": "artifacts/mangiferin-research/22815239.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e85ebd0af89f030dbeda45ed922e93a8a616c51f5ce1b64badc44d90791716c0", "start_char": 0, "end_char": 1728, "text_sha256": "e85ebd0af89f030dbeda45ed922e93a8a616c51f5ce1b64badc44d90791716c0"}

experimental_model

Primary human hepatocyte exposure

exposure

Mangiferin 50-250 micrograms/mL for 48 hours

limitations

High in vitro concentrations; decreased enzyme activity is not proof of human drug-level changes. Extract and isolated mangiferin are distinct.

nutrient_topic

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

organism

Homo sapiens

plain_language

A drug-metabolizing enzyme was inhibited under the tested exposure.

primary_references

[mangiferin-p22815239] Mangifera indica L. extract and mangiferin modulate cytochrome P450 and UDP-glucuronosyltransferase enzymes in primary cultures of human hepatocytes. (2013). https://pubmed.ncbi.nlm.nih.gov/22815239/ DOI: 10.1002/ptr.4782

tissue_or_cell_type

Cultured hepatocytes

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 822–833

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human hepatocyte exposure · source_derived_draft · unverified_draft

### mangiferin-cyp3a4-activity Mangiferin reduced measured CYP3A4 activity in the hepatocyte experiment. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A drug-metabolizing enzyme was inhibited under the tested exposure. organism: Homo sapiens tissue_or_cell_type: Cultured hepatocytes experimental_model: Primary human hepatocyte exposure limitations: High in vitro concentrations; decreased enzyme activity is not proof of human drug-level changes. Extract and isolated mangiferin are distinct. exposure: Mangiferin 50-250 micrograms/mL for 48 hours evidence_span: {"source_cache": "artifacts/mangiferin-research/22815239.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e85ebd0af89f030dbeda45ed922e93a8a616c51f5ce1b64badc44d90791716c0", "start_char": 0, "end_char": 1728, "text_sha256": "e85ebd0af89f030dbeda45ed922e93a8a616c51f5ce1b64badc44d90791716c0"} [mangiferin-p22815239] Mangifera indica L. extract and mangiferin modulate cytochrome P450 and UDP-glucuronosyltransferase enzymes in primary cultures of human hepatocytes. (2013). https://pubmed.ncbi.nlm.nih.gov/22815239/ DOI: 10.1002/ptr.4782

evidence_access

Primary full text PMC3513969, CYP methods and results

experimental_model

Human liver microsomes; product concentrations normalized to 0.5–25 micromolar lovastatin, with an NADPH-generating system.

limitations

In-vitro inhibition is not a measured interaction with every drug using this enzyme; the additional responsible constituent was not identified.

nutrient_topic

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

plain_language

The mixture changed an enzyme assay beyond its lovastatin content.

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 124–130

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human liver microsomes; product concentrations normalized to 0.5–25 micromolar lovastatin, with an NADPH-generating system. · source_derived_draft · unverified_draft

## red-yeast-rice-extract-cyp3a4 The mixture changed an enzyme assay beyond its lovastatin content. The three 2012 red yeast rice product extracts inhibited human microsomal CYP3A4 more potently than pure lovastatin at matched nominal lovastatin concentrations. Model: Human liver microsomes; product concentrations normalized to 0.5–25 micromolar lovastatin, with an NADPH-generating system. Limitations: In-vitro inhibition is not a measured interaction with every drug using this enzyme; the additional responsible constituent was not identified. Evidence access: Primary full text PMC3513969, CYP methods and results [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_access

Primary full text

experimental_model

42 initiated; enzyme activities assessed in 40; before/after pharmacological-dose study.

limitations

Probe indices are not proof of transcriptional induction or a quantified interaction with every substrate; no medication adjustment follows.

nutrient_topic

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

plain_language

A human drug-metabolism interaction was measured with a specific probe.

primary_references

Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20716633/ · DOI 10.1158/1940-6207.CAPR-09-0155

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 438–444

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 42 initiated; enzyme activities assessed in 40; before/after pharmacological-dose study. · source_derived_draft · unverified_draft

## resveratrol-human-cyp3a4 A human drug-metabolism interaction was measured with a specific probe. After 1 g/day resveratrol for four weeks, the healthy-volunteer study found decreased CYP3A4 phenotypic activity using buspirone as the probe. Model: 42 initiated; enzyme activities assessed in 40; before/after pharmacological-dose study. Limitations: Probe indices are not proof of transcriptional induction or a quantified interaction with every substrate; no medication adjustment follows. Evidence access: Primary full text Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20716633/ · DOI 10.1158/1940-6207.CAPR-09-0155

evidence_span

{"source_cache": "artifacts/curcumin-research/18480186.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1155ca38a767b3c3fa7bd494d0ad5590eed70a47812b7a6f3d977b43aa8a922", "start_char": 0, "end_char": 1788, "text_sha256": "c1155ca38a767b3c3fa7bd494d0ad5590eed70a47812b7a6f3d977b43aa8a922"}

experimental_model

Human microsomal/cytosolic and recombinant enzyme inhibition assays

exposure

Curcuminoid mixture, purified curcuminoids and piperine; micromolar concentrations

limitations

In-vitro inhibition does not automatically predict human drug levels. Extract, isolated curcumin and piperine are separate interventions.

nutrient_topic

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

organism

Human enzyme systems

plain_language

The added absorption enhancer has its own enzyme effects.

primary_references

[curcumin-p18480186] Curcuminoids inhibit multiple human cytochromes P450, UDP-glucuronosyltransferase, and sulfotransferase enzymes, whereas piperine is a relatively selective CYP3A4 inhibitor. (2008). https://pubmed.ncbi.nlm.nih.gov/18480186/ DOI: 10.1124/dmd.108.020552

tissue_or_cell_type

Drug metabolism assays

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 905–916

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomal/cytosolic and recombinant enzyme inhibition assays · source_derived_draft · unverified_draft

### curcumin-piperine-cyp3a4 Piperine inhibited recombinant CYP3A4 more potently than CYP3A5. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The added absorption enhancer has its own enzyme effects. organism: Human enzyme systems tissue_or_cell_type: Drug metabolism assays experimental_model: Human microsomal/cytosolic and recombinant enzyme inhibition assays limitations: In-vitro inhibition does not automatically predict human drug levels. Extract, isolated curcumin and piperine are separate interventions. exposure: Curcuminoid mixture, purified curcuminoids and piperine; micromolar concentrations evidence_span: {"source_cache": "artifacts/curcumin-research/18480186.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1155ca38a767b3c3fa7bd494d0ad5590eed70a47812b7a6f3d977b43aa8a922", "start_char": 0, "end_char": 1788, "text_sha256": "c1155ca38a767b3c3fa7bd494d0ad5590eed70a47812b7a6f3d977b43aa8a922"} [curcumin-p18480186] Curcuminoids inhibit multiple human cytochromes P450, UDP-glucuronosyltransferase, and sulfotransferase enzymes, whereas piperine is a relatively selective CYP3A4 inhibitor. (2008). https://pubmed.ncbi.nlm.nih.gov/18480186/ DOI: 10.1124/dmd.108.020552

evidence_access

Primary full text

experimental_model

Recombinant human enzymes; 5 micromolar substrate.

limitations

Restricted substrate, concentration and preparation; earlier CYP2C9 assays gave different potency.

nutrient_topic

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

plain_language

A transporter interaction does not imply strong CYP inhibition.

primary_references

Interaction of myricetin, ampelopsin (dihydromyricetin), and their sulfate metabolites with serum albumin, cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes, and organic anion-transporting polypeptides (OATP1B1 and OATP2B1). · 2024 · https://pubmed.ncbi.nlm.nih.gov/39344282/ · DOI 10.1002/prp2.70021

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 148–154

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzymes; 5 micromolar substrate. · source_derived_draft · unverified_draft

## myricetin-parent-cyp3a4 A transporter interaction does not imply strong CYP inhibition. At 20 micromolar, the parent reduced testosterone hydroxylation by less than 10% in the human CYP3A4 assay. Model: Recombinant human enzymes; 5 micromolar substrate. Limitations: Restricted substrate, concentration and preparation; earlier CYP2C9 assays gave different potency. Evidence access: Primary full text Interaction of myricetin, ampelopsin (dihydromyricetin), and their sulfate metabolites with serum albumin, cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes, and organic anion-transporting polypeptides (OATP1B1 and OATP2B1). · 2024 · https://pubmed.ncbi.nlm.nih.gov/39344282/ · DOI 10.1002/prp2.70021

evidence_access

Primary full text

experimental_model

Recombinant human enzymes; 5 micromolar substrate.

limitations

Restricted substrate, concentration and preparation; earlier CYP2C9 assays gave different potency.

nutrient_topic

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

plain_language

A transporter interaction does not imply strong CYP inhibition.

primary_references

Interaction of myricetin, ampelopsin (dihydromyricetin), and their sulfate metabolites with serum albumin, cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes, and organic anion-transporting polypeptides (OATP1B1 and OATP2B1). · 2024 · https://pubmed.ncbi.nlm.nih.gov/39344282/ · DOI 10.1002/prp2.70021

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 196–202

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzymes; 5 micromolar substrate. · source_derived_draft · unverified_draft

## myricetin-sulfate-cyp3a4 A transporter interaction does not imply strong CYP inhibition. At 20 micromolar, the sulfate reduced testosterone hydroxylation by less than 10% in the human CYP3A4 assay. Model: Recombinant human enzymes; 5 micromolar substrate. Limitations: Restricted substrate, concentration and preparation; earlier CYP2C9 assays gave different potency. Evidence access: Primary full text Interaction of myricetin, ampelopsin (dihydromyricetin), and their sulfate metabolites with serum albumin, cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes, and organic anion-transporting polypeptides (OATP1B1 and OATP2B1). · 2024 · https://pubmed.ncbi.nlm.nih.gov/39344282/ · DOI 10.1002/prp2.70021

evidence_access

Primary abstract

experimental_model

Primary human hepatocyte exposure experiment.

limitations

Cell induction is not a demonstrated clinical drug interaction; no automatic prediction of drug clearance or dose adjustment.

nutrient_topic

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

plain_language

Human liver cells showed a selective enzyme response.

primary_references

Metabolism and CYP-inducer properties of astaxanthin in man and primary human hepatocytes. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11876499/ · DOI 10.1007/s00204-001-0287-5

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 134–140

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Primary human hepatocyte exposure experiment. · source_derived_draft · unverified_draft

## astaxanthin-cyp-induction Human liver cells showed a selective enzyme response. Astaxanthin induced CYP3A4 and CYP2B6 in cultured primary human hepatocytes, without the CYP1A/CYP2C induction reported in rat comparisons. Model: Primary human hepatocyte exposure experiment. Limitations: Cell induction is not a demonstrated clinical drug interaction; no automatic prediction of drug clearance or dose adjustment. Evidence access: Primary abstract Metabolism and CYP-inducer properties of astaxanthin in man and primary human hepatocytes. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11876499/ · DOI 10.1007/s00204-001-0287-5

acting_entity

s-allylcysteine

dose

SAC 0.01–1 mM; N-acetyl-SAC 1 mM

duration

Probe-specific incubation

evidence_access

Primary full-text HTML, methods/results

experimental_comparison

Test compound versus probe reaction without compound

experimental_model

Pooled human liver microsomes; probe substrate metabolism

interpretation_status

Source-derived research curation; not independent primary verification

limitations

Microsomal assay; not a clinical interaction or induction study.

nutrient_topic

S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC

organism

Human liver preparation

plain_language

A negative enzyme-interaction result is retained.

primary_references

[27725449] Evaluation of the Effects of S-Allyl-L-cysteine, S-Methyl-L-cysteine, trans-S-1-Propenyl-L-cysteine, and Their N-Acetylated and S-Oxidized Metabolites on Human CYP Activities. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27725449/ · DOI 10.1248/bpb.b16-00449

route

In vitro

tissue_or_cell_type

Pooled human liver microsomes; probe substrate metabolism

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 419–426

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pooled human liver microsomes; probe substrate metabolism · source_derived_draft · unverified_draft

## s-allylcysteine-cyp-null-cyp3a4 A negative enzyme-interaction result is retained. SAC showed little effect on tested human CYP3A4 activity over 0.01–1 mM. Model: Pooled human liver microsomes; probe substrate metabolism Limitations: Microsomal assay; not a clinical interaction or induction study. Evidence access: Primary full-text HTML, methods/results [27725449] Evaluation of the Effects of S-Allyl-L-cysteine, S-Methyl-L-cysteine, trans-S-1-Propenyl-L-cysteine, and Their N-Acetylated and S-Oxidized Metabolites on Human CYP Activities. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27725449/ · DOI 10.1248/bpb.b16-00449 Structured context: {"organism": "Human liver preparation", "tissue_or_cell_type": "Pooled human liver microsomes; probe substrate metabolism", "dose": "SAC 0.01–1 mM; N-acetyl-SAC 1 mM", "duration": "Probe-specific incubation", "route": "In vitro", "experimental_comparison": "Test compound versus probe reaction without compound", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

evidence_span

{"source_cache": "artifacts/thc-research/38583809.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1", "start_char": 0, "end_char": 1645, "text_sha256": "29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1"}

experimental_model

Recombinant enzyme metabolism of THC with and without liver fatty acid binding protein

exposure

THC metabolism by CYP2C9, CYP3A and CYP2C19 with FABP1

limitations

Adds a binding protein that changes apparent metabolism, which matters because THC is extremely lipophilic. It is a recombinant system.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Human enzymes

plain_language

Three enzymes share the job, and a fat-carrying protein changes how fast they do it.

primary_references

[thc-p38583809] CYP2C9, CYP3A and CYP2C19 metabolize Δ9-tetrahydrocannabinol to multiple metabolites but metabolism is affected by human liver fatty acid binding protein (FABP1). (2024). https://pubmed.ncbi.nlm.nih.gov/38583809/ DOI: 10.1016/j.bcp.2024.116191

tissue_or_cell_type

Recombinant system

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 543–554

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme metabolism of THC with and without liver fatty acid binding protein · source_derived_draft · unverified_draft

### thc-multiple-cyps CYP2C9, CYP3A and CYP2C19 metabolised THC to multiple metabolites, but the metabolism was affected by human liver fatty acid binding protein. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Three enzymes share the job, and a fat-carrying protein changes how fast they do it. organism: Human enzymes tissue_or_cell_type: Recombinant system experimental_model: Recombinant enzyme metabolism of THC with and without liver fatty acid binding protein limitations: Adds a binding protein that changes apparent metabolism, which matters because THC is extremely lipophilic. It is a recombinant system. exposure: THC metabolism by CYP2C9, CYP3A and CYP2C19 with FABP1 evidence_span: {"source_cache": "artifacts/thc-research/38583809.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1", "start_char": 0, "end_char": 1645, "text_sha256": "29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1"} [thc-p38583809] CYP2C9, CYP3A and CYP2C19 metabolize Δ9-tetrahydrocannabinol to multiple metabolites but metabolism is affected by human liver fatty acid binding protein (FABP1). (2024). https://pubmed.ncbi.nlm.nih.gov/38583809/ DOI: 10.1016/j.bcp.2024.116191

dose

Leaf extracts from 0.01 to 10 mg/mL

duration

Incubation interval specified in the primary article

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Mixed-sex human liver microsomes

limitations

Extract concentrations and microsomal inhibition do not predict a clinical interaction without constituent exposure and intestinal/hepatic concentrations.

nutrient_topic

Moringa oleifera chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Moringa oleifera

organism

Mixed-sex human liver microsomes

plain_language

Moringa methanolic and aqueous leaf extracts inhibited CYP3A4-mediated testosterone 6-beta-hydroxylation in mixed-sex human liver microsomes, with reported IC50 values of 0.5 and 2.5 mg/mL.

primary_references

Moringa oleifera leaf extracts inhibit 6beta-hydroxylation of testosterone by CYP3A4. (2008). https://pubmed.ncbi.nlm.nih.gov/19745507/ DOI: 10.3855/jidc.201

route

In vitro

tissue

CYP3A4 testosterone 6-beta-hydroxylation

Moringa oleifera: mechanism of action and interactions (2026-09-20) · lines 200–209

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Mixed-sex human liver microsomes · source_derived_draft · unverified_draft

## moringa-leaf-extract-cyp3a4 Moringa methanolic and aqueous leaf extracts inhibited CYP3A4-mediated testosterone 6-beta-hydroxylation in mixed-sex human liver microsomes, with reported IC50 values of 0.5 and 2.5 mg/mL. Model/species: Mixed-sex human liver microsomes Tissue/system: CYP3A4 testosterone 6-beta-hydroxylation Exposure: Leaf extracts from 0.01 to 10 mg/mL Route: In vitro Duration: Incubation interval specified in the primary article Limits: Extract concentrations and microsomal inhibition do not predict a clinical interaction without constituent exposure and intestinal/hepatic concentrations. Primary reference: Moringa oleifera leaf extracts inhibit 6beta-hydroxylation of testosterone by CYP3A4. (2008). https://pubmed.ncbi.nlm.nih.gov/19745507/ DOI: 10.3855/jidc.201 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Nevirapine alone then with 1.85 g/day Moringa leaf powder

duration

14 days coadministration

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Adults with HIV receiving steady-state nevirapine

limitations

The small one-sequence study supports a null at this product and dose, not absence of interaction with every drug or preparation.

nutrient_topic

Moringa oleifera chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Moringa oleifera

organism

Adults with HIV receiving steady-state nevirapine

plain_language

In eleven evaluable adults with HIV, 1.85 g/day Moringa leaf powder for 14 days did not significantly alter steady-state nevirapine AUC, Cmax or 12-hour concentration.

primary_references

Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study. (2017). https://pubmed.ncbi.nlm.nih.gov/28293270/ DOI: 10.1186/s12981-017-0140-4

route

Oral

tissue

Intensive 12-hour nevirapine pharmacokinetics

Moringa oleifera: mechanism of action and interactions (2026-09-20) · lines 178–187

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Adults with HIV receiving steady-state nevirapine · source_derived_draft · unverified_draft

## moringa-nevirapine-pk-null In eleven evaluable adults with HIV, 1.85 g/day Moringa leaf powder for 14 days did not significantly alter steady-state nevirapine AUC, Cmax or 12-hour concentration. Model/species: Adults with HIV receiving steady-state nevirapine Tissue/system: Intensive 12-hour nevirapine pharmacokinetics Exposure: Nevirapine alone then with 1.85 g/day Moringa leaf powder Route: Oral Duration: 14 days coadministration Limits: The small one-sequence study supports a null at this product and dose, not absence of interaction with every drug or preparation. Primary reference: Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study. (2017). https://pubmed.ncbi.nlm.nih.gov/28293270/ DOI: 10.1186/s12981-017-0140-4 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_access

Primary abstract

experimental_model

Human CYP assays.

limitations

Restricted enzyme panel; not a blanket absence of interactions.

nutrient_topic

Luteolin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Luteolin / 3′,4′,5,7-tetrahydroxyflavone

plain_language

The parent’s effects cannot simply be assigned to every metabolite.

primary_references

Interaction of luteolin, naringenin, and their sulfate and glucuronide conjugates with human serum albumin, cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) enzymes and organic anion transporting polypeptide (OATP1B1 and OATP2B1) transporters. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36481402/ · DOI 10.1016/j.biopha.2022.114078

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 244–250

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human CYP assays. · source_derived_draft · unverified_draft

## luteolin-conjugate-cyp The parent’s effects cannot simply be assigned to every metabolite. Tested luteolin conjugates had no or weak inhibition of CYP2C9, CYP2C19 and CYP3A4. Model: Human CYP assays. Limitations: Restricted enzyme panel; not a blanket absence of interactions. Evidence access: Primary abstract Interaction of luteolin, naringenin, and their sulfate and glucuronide conjugates with human serum albumin, cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) enzymes and organic anion transporting polypeptide (OATP1B1 and OATP2B1) transporters. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36481402/ · DOI 10.1016/j.biopha.2022.114078

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sildenafil-research/10546851.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a789c249a680590fd363d884785a531062441be8e2442ec872fa832dc43b7504", "start_char": 0, "end_char": 2556, "text_sha256": "a789c249a680590fd363d884785a531062441be8e2442ec872fa832dc43b7504"}

experimental_model

Open pharmacokinetic study in six patients at steady state on a protease inhibitor, with a parallel in vitro metabolism arm

exposure

A single 25 milligram dose of sildenafil added to steady-state indinavir, with plasma sampling to eight hours

limitations

Six patients and no concurrent control group: the sildenafil exposure is compared with dose-normalised historical controls rather than with the same patients off indinavir.

nutrient_topic

Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil

organism

Human

plain_language

A drug that blocks the same liver enzyme left more than four times as much of it in the blood.

primary_references

[sil-p10546851] Interaction of sildenafil and indinavir when co-administered to HIV-positive patients. (1999). https://pubmed.ncbi.nlm.nih.gov/10546851/ DOI: 10.1097/00002030-199910220-00001

tissue_or_cell_type

Systemic circulation and liver microsomes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 470–481

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Open pharmacokinetic study in six patients at steady state on a protease inhibitor, with a parallel in vitro metabolism arm · source_derived_draft · unverified_draft

### sil-protease-inhibitor-quadruples-exposure In six HIV-infected patients at steady state on indinavir a single 25 milligram dose of sildenafil did not significantly alter plasma indinavir concentrations, but the geometric mean area under the sildenafil concentration curve of 1631 nanograms per millilitre hour was 4.4 times higher than data from historical controls given either 50 or 100 milligrams and dose normalised to 25 milligrams, and in a parallel study indinavir was a potent inhibitor of sildenafil hepatic metabolism in vitro with a half-maximal inhibitory concentration of 0.39 micromolar, so that the mechanism of the increase is inhibition of hepatic metabolism and a lower starting dose may be more appropriate in this setting. Condition category: machinery_impairment nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: A drug that blocks the same liver enzyme left more than four times as much of it in the blood. organism: Human tissue_or_cell_type: Systemic circulation and liver microsomes experimental_model: Open pharmacokinetic study in six patients at steady state on a protease inhibitor, with a parallel in vitro metabolism arm limitations: Six patients and no concurrent control group: the sildenafil exposure is compared with dose-normalised historical controls rather than with the same patients off indinavir. exposure: A single 25 milligram dose of sildenafil added to steady-state indinavir, with plasma sampling to eight hours evidence_span: {"source_cache": "artifacts/sildenafil-research/10546851.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a789c249a680590fd363d884785a531062441be8e2442ec872fa832dc43b7504", "start_char": 0, "end_char": 2556, "text_sha256": "a789c249a680590fd363d884785a531062441be8e2442ec872fa832dc43b7504"} [sil-p10546851] Interaction of sildenafil and indinavir when co-administered to HIV-positive patients. (1999). https://pubmed.ncbi.nlm.nih.gov/10546851/ DOI: 10.1097/00002030-199910220-00001

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sildenafil-research/10078541.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e65228d2afaad9ce38dccf42c7279ec6b562746aa27b121bf5e5782f36cbe593", "start_char": 0, "end_char": 2772, "text_sha256": "e65228d2afaad9ce38dccf42c7279ec6b562746aa27b121bf5e5782f36cbe593"}

experimental_model

Review of the cardiovascular profile from the clinical development programme and post-marketing surveillance

exposure

Sildenafil alone and with antihypertensive classes, across clinical trials and spontaneous reports

limitations

A manufacturer-authored review of the development programme rather than an independent analysis, and the post-marketing comparisons are retrospective.

nutrient_topic

Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil

organism

Human

plain_language

Both act on the same pathway at different points, which is why together they multiply rather than add.

primary_references

[sil-p10078541] Overall cardiovascular profile of sildenafil citrate. (1999). https://pubmed.ncbi.nlm.nih.gov/10078541/ DOI: 10.1016/s0002-9149(99)00046-6

tissue_or_cell_type

Cardiovascular system

trigger_kind

biomarker_context Imported condition classification; unverified.

Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 431–442

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of the cardiovascular profile from the clinical development programme and post-marketing surveillance · source_derived_draft · unverified_draft

### sil-two-points-on-one-pathway Sildenafil alone can cause mean peak reductions in systolic and diastolic blood pressure of 10 and 7 millimetres of mercury that are not dose related while heart rate is unchanged, and sildenafil and nitrates both increase cyclic GMP levels in the systemic circulation but at different points along the nitric oxide to cyclic GMP pathway, so the combination is contraindicated because they synergistically potentiate vasodilation; retrospective analysis of concomitant antihypertensive medications did not indicate an increase in adverse events, and concurrent renal or hepatic impairment or CYP3A4 inhibitors could increase systemic exposure. Condition category: biomarker_context nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: Both act on the same pathway at different points, which is why together they multiply rather than add. organism: Human tissue_or_cell_type: Cardiovascular system experimental_model: Review of the cardiovascular profile from the clinical development programme and post-marketing surveillance limitations: A manufacturer-authored review of the development programme rather than an independent analysis, and the post-marketing comparisons are retrospective. exposure: Sildenafil alone and with antihypertensive classes, across clinical trials and spontaneous reports evidence_span: {"source_cache": "artifacts/sildenafil-research/10078541.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e65228d2afaad9ce38dccf42c7279ec6b562746aa27b121bf5e5782f36cbe593", "start_char": 0, "end_char": 2772, "text_sha256": "e65228d2afaad9ce38dccf42c7279ec6b562746aa27b121bf5e5782f36cbe593"} [sil-p10078541] Overall cardiovascular profile of sildenafil citrate. (1999). https://pubmed.ncbi.nlm.nih.gov/10078541/ DOI: 10.1016/s0002-9149(99)00046-6

evidence_span

{"source_cache": "artifacts/sulforaphane-research/23153560.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec", "start_char": 0, "end_char": 1664, "text_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec"}

experimental_model

Three-arm randomized crossover trial

exposure

Rifampicin 300 mg/day, with or without sulforaphane 450 micromol/day for seven days; sulforaphane alone

limitations

Average null result does not exclude individual or other-drug interactions; high-baseline subgroup finding is not a dosing rule.

nutrient_topic

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

organism

Human, 24 healthy adults; humanized-PXR mouse parallel study

plain_language

An average null and an exploratory subgroup signal must both remain visible.

primary_references

[sulforaphane-p23153560] Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo. (2013). https://pubmed.ncbi.nlm.nih.gov/23153560/ DOI: 10.1016/j.taap.2012.10.029

tissue_or_cell_type

CYP3A phenotyping with midazolam

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1269–1280

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-arm randomized crossover trial · source_derived_draft · unverified_draft

### sulforaphane-cyp3a4-alone-null Sulforaphane alone did not change CYP3A activity in the cohort overall; a high-baseline subgroup showed increased midazolam exposure. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: An average null and an exploratory subgroup signal must both remain visible. organism: Human, 24 healthy adults; humanized-PXR mouse parallel study tissue_or_cell_type: CYP3A phenotyping with midazolam experimental_model: Three-arm randomized crossover trial limitations: Average null result does not exclude individual or other-drug interactions; high-baseline subgroup finding is not a dosing rule. exposure: Rifampicin 300 mg/day, with or without sulforaphane 450 micromol/day for seven days; sulforaphane alone evidence_span: {"source_cache": "artifacts/sulforaphane-research/23153560.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec", "start_char": 0, "end_char": 1664, "text_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec"} [sulforaphane-p23153560] Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo. (2013). https://pubmed.ncbi.nlm.nih.gov/23153560/ DOI: 10.1016/j.taap.2012.10.029

evidence_span

{"source_cache": "artifacts/sulforaphane-research/23153560.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec", "start_char": 0, "end_char": 1664, "text_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec"}

experimental_model

Three-arm randomized crossover trial

exposure

Rifampicin 300 mg/day, with or without sulforaphane 450 micromol/day for seven days; sulforaphane alone

limitations

Average null result does not exclude individual or other-drug interactions; high-baseline subgroup finding is not a dosing rule.

nutrient_topic

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

organism

Human, 24 healthy adults; humanized-PXR mouse parallel study

plain_language

The proposed receptor-blocking effect from laboratory work did not carry through in the human trial.

primary_references

[sulforaphane-p23153560] Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo. (2013). https://pubmed.ncbi.nlm.nih.gov/23153560/ DOI: 10.1016/j.taap.2012.10.029

tissue_or_cell_type

CYP3A phenotyping with midazolam

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1256–1267

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-arm randomized crossover trial · source_derived_draft · unverified_draft

### sulforaphane-cyp3a4-rifampicin-null Coadministration did not prevent rifampicin-driven CYP3A induction; rifampicin alone lowered midazolam AUC by 70%. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The proposed receptor-blocking effect from laboratory work did not carry through in the human trial. organism: Human, 24 healthy adults; humanized-PXR mouse parallel study tissue_or_cell_type: CYP3A phenotyping with midazolam experimental_model: Three-arm randomized crossover trial limitations: Average null result does not exclude individual or other-drug interactions; high-baseline subgroup finding is not a dosing rule. exposure: Rifampicin 300 mg/day, with or without sulforaphane 450 micromol/day for seven days; sulforaphane alone evidence_span: {"source_cache": "artifacts/sulforaphane-research/23153560.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec", "start_char": 0, "end_char": 1664, "text_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec"} [sulforaphane-p23153560] Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo. (2013). https://pubmed.ncbi.nlm.nih.gov/23153560/ DOI: 10.1016/j.taap.2012.10.029

evidence_access

Primary abstract

experimental_model

Randomized crossover: 200 mL three times daily for two days, with further juice around the day-three dose.

limitations

Prescription lovastatin and intensive juice regimen; not a measured red yeast rice interaction or a multiplier for ordinary juice intake.

nutrient_topic

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

plain_language

Food-related inhibition of first-pass handling can change drug exposure.

primary_references

[9585793] Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9585793/ · DOI 10.1016/S0009-9236(98)90034-0

Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 180–186

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized crossover: 200 mL three times daily for two days, with further juice around the day-three dose. · source_derived_draft · unverified_draft

## red-yeast-rice-grapefruit-lovastatin Food-related inhibition of first-pass handling can change drug exposure. Repeated double-strength grapefruit juice increased lovastatin peak concentration about 12-fold and exposure area about 15-fold after an 80 mg dose in ten volunteers. Model: Randomized crossover: 200 mL three times daily for two days, with further juice around the day-three dose. Limitations: Prescription lovastatin and intensive juice regimen; not a measured red yeast rice interaction or a multiplier for ordinary juice intake. Evidence access: Primary abstract [9585793] Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9585793/ · DOI 10.1016/S0009-9236(98)90034-0

evidence_access

Primary abstract

experimental_model

Randomized crossover prescription-lovastatin study; lovastatin-acid exposure also increased.

limitations

The numerical magnitude belongs to this drug regimen, not to untested red yeast rice preparations.

nutrient_topic

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

plain_language

A drug interaction can substantially change constituent exposure.

primary_references

[9690949] Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9690949/ · DOI 10.1046/j.1365-2125.1998.00034.x

Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 196–202

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized crossover prescription-lovastatin study; lovastatin-acid exposure also increased. · source_derived_draft · unverified_draft

## red-yeast-rice-itraconazole A drug interaction can substantially change constituent exposure. Itraconazole 100 mg daily for four days increased lovastatin peak concentration about 15-fold and exposure area more than 15-fold after a 40 mg dose in ten volunteers. Model: Randomized crossover prescription-lovastatin study; lovastatin-acid exposure also increased. Limitations: The numerical magnitude belongs to this drug regimen, not to untested red yeast rice preparations. Evidence access: Primary abstract [9690949] Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9690949/ · DOI 10.1046/j.1365-2125.1998.00034.x

evidence_access

Primary full text PMC3513969

experimental_model

Human fasted-state single-dose pharmacokinetic comparison.

limitations

A null result for this dose does not exclude other drugs, preparations or exposures.

nutrient_topic

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

plain_language

The predicted enzyme interaction was not demonstrated in this tested regimen.

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 156–162

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human fasted-state single-dose pharmacokinetic comparison. · source_derived_draft · unverified_draft

## red-yeast-rice-nifedipine-null The predicted enzyme interaction was not demonstrated in this tested regimen. One 600 mg LipoCol Forte capsule did not significantly change the measured pharmacokinetics of 5 mg nifedipine in 14 volunteers. Model: Human fasted-state single-dose pharmacokinetic comparison. Limitations: A null result for this dose does not exclude other drugs, preparations or exposures. 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

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experimental_model

Ligand binding, gene expression and receptor-null mouse cells

exposure

Vitamin K2 exposure and receptor deficiency

limitations

Preclinical transcription effects; supplement-level target engagement in people is not established. Abstract calls the tested ligand K2 without distinguishing every homologue.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human osteosarcoma cells and mouse calvarial cells

plain_language

K2 can have a receptor-signaling role separate from protein carboxylation.

primary_references

[k2-p12920130] Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. (2003). https://pubmed.ncbi.nlm.nih.gov/12920130/ DOI: 10.1074/jbc.m303136200

tissue_or_cell_type

SXR/PXR transcription

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 695–706

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand binding, gene expression and receptor-null mouse cells · source_derived_draft · unverified_draft

### k2-k2-sxr Vitamin K2 bound and activated human SXR and induced its CYP3A4 target gene in the tested system. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: K2 can have a receptor-signaling role separate from protein carboxylation. organism: Human osteosarcoma cells and mouse calvarial cells tissue_or_cell_type: SXR/PXR transcription experimental_model: Ligand binding, gene expression and receptor-null mouse cells limitations: Preclinical transcription effects; supplement-level target engagement in people is not established. Abstract calls the tested ligand K2 without distinguishing every homologue. exposure: Vitamin K2 exposure and receptor deficiency evidence_span: {"source_cache": "artifacts/k2-research/12920130.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617", "start_char": 0, "end_char": 1589, "text_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617"} [k2-p12920130] Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. (2003). https://pubmed.ncbi.nlm.nih.gov/12920130/ DOI: 10.1074/jbc.m303136200

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

dose

Tyrosol with selective CYP inhibitors or recombinant enzymes

duration

Enzyme incubation

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human liver microsomes, recombinant CYPs, genotyped livers and rat control experiments

limitations

Relative contribution varies by genotype and setting; this does not make every tyrosol food equivalent to hydroxytyrosol dosing.

nutrient_topic

Hydroxytyrosol chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Hydroxytyrosol

organism

Human liver microsomes, recombinant CYPs, genotyped livers and rat control experiments

plain_language

Human liver microsomes and recombinant enzymes converted tyrosol to hydroxytyrosol, with CYP2A6 and CYP2D6 supported as major contributors and CYP3A4 also active in baculosomes.

primary_references

CYP2D6 and CYP2A6 biotransform dietary tyrosol into hydroxytyrosol. (2017). https://pubmed.ncbi.nlm.nih.gov/27664690/ DOI: 10.1016/j.foodchem.2016.09.026

route

In vitro and in vivo experimental metabolism

tissue

Tyrosol hydroxylation

Hydroxytyrosol: mechanism of action and interactions (2026-09-20) · lines 44–53

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human liver microsomes, recombinant CYPs, genotyped livers and rat control experiments · source_derived_draft · unverified_draft

## hydroxytyrosol-tyrosol-cyp-conversion Human liver microsomes and recombinant enzymes converted tyrosol to hydroxytyrosol, with CYP2A6 and CYP2D6 supported as major contributors and CYP3A4 also active in baculosomes. Model/species: Human liver microsomes, recombinant CYPs, genotyped livers and rat control experiments Tissue/system: Tyrosol hydroxylation Exposure: Tyrosol with selective CYP inhibitors or recombinant enzymes Route: In vitro and in vivo experimental metabolism Duration: Enzyme incubation Limits: Relative contribution varies by genotype and setting; this does not make every tyrosol food equivalent to hydroxytyrosol dosing. Primary reference: CYP2D6 and CYP2A6 biotransform dietary tyrosol into hydroxytyrosol. (2017). https://pubmed.ncbi.nlm.nih.gov/27664690/ DOI: 10.1016/j.foodchem.2016.09.026 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.