Human cytochrome P450 2D6

evidence_span

{"source_cache": "artifacts/dim-research/8591723.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e", "start_char": 0, "end_char": 1460, "text_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e"}

experimental_model

Human microsomes and individually expressed enzymes

exposure

Enzyme-specific inhibitors and radiolabeled substrate

limitations

CYP3A is identified at subfamily level, without an exclusive isoform assignment. Multiple CYP pathways contribute; no DIM coadministration or clinically measured DIM effect.

nutrient_topic

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

organism

Human CYP systems

plain_language

A substrate list alone omits other routes that can limit a single-enzyme interaction.

primary_references

[dim-p8591723] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/8591723/ DOI: 10.1016/s0090-9556(25)06820-5

tissue_or_cell_type

Ondansetron oxidation

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 961–972

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomes and individually expressed enzymes · source_derived_draft · unverified_draft

### dim-ondansetron-cyp2d6 CYP2D6 contributed to ondansetron metabolism in the studied human systems. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A substrate list alone omits other routes that can limit a single-enzyme interaction. organism: Human CYP systems tissue_or_cell_type: Ondansetron oxidation experimental_model: Human microsomes and individually expressed enzymes limitations: CYP3A is identified at subfamily level, without an exclusive isoform assignment. Multiple CYP pathways contribute; no DIM coadministration or clinically measured DIM effect. exposure: Enzyme-specific inhibitors and radiolabeled substrate evidence_span: {"source_cache": "artifacts/dim-research/8591723.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e", "start_char": 0, "end_char": 1460, "text_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e"} [dim-p8591723] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/8591723/ DOI: 10.1016/s0090-9556(25)06820-5

evidence_span

{"source_cache": "artifacts/dim-research/7640150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247", "start_char": 0, "end_char": 2428, "text_sha256": "368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247"}

experimental_model

Human microsomes and recombinant enzyme phenotyping

exposure

N-desisopropylation versus ring hydroxylation

limitations

Route- and enantiomer-specific biochemistry; total propranolol exposure cannot be predicted from one route.

nutrient_topic

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

organism

Human CYP isoforms

plain_language

A separate enzyme supports a different transformation of the same drug.

primary_references

[dim-p7640150] Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers--N-desisopropylation is mediated mainly by CYP1A2. (1995). https://pubmed.ncbi.nlm.nih.gov/7640150/ DOI: 10.1111/j.1365-2125.1995.tb04472.x

tissue_or_cell_type

Propranolol enantiomer metabolism

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 922–933

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

### dim-propranolol-2d6 CYP2D6 was a major catalyst of propranolol ring 4-hydroxylation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate enzyme supports a different transformation of the same drug. organism: Human CYP isoforms tissue_or_cell_type: Propranolol enantiomer metabolism experimental_model: Human microsomes and recombinant enzyme phenotyping limitations: Route- and enantiomer-specific biochemistry; total propranolol exposure cannot be predicted from one route. exposure: N-desisopropylation versus ring hydroxylation evidence_span: {"source_cache": "artifacts/dim-research/7640150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247", "start_char": 0, "end_char": 2428, "text_sha256": "368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247"} [dim-p7640150] Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers--N-desisopropylation is mediated mainly by CYP1A2. (1995). https://pubmed.ncbi.nlm.nih.gov/7640150/ DOI: 10.1111/j.1365-2125.1995.tb04472.x

evidence_span

{"source_cache": "artifacts/dim-research/15159443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081", "start_char": 0, "end_char": 1544, "text_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081"}

experimental_model

Kinetic, inhibition and recombinant-enzyme pathway mapping

exposure

Therapeutically relevant substrate concentrations

limitations

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

nutrient_topic

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

organism

Human liver microsomes and expressed CYPs

plain_language

Parent-drug removal and active-metabolite formation can move differently.

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 1013–1024

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-4oh CYP2D6 and other CYPs formed 4-hydroxytamoxifen through a smaller initial route. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Parent-drug removal and active-metabolite formation can move differently. 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

evidence_span

{"source_cache": "artifacts/dim-research/15159443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081", "start_char": 0, "end_char": 1544, "text_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081"}

experimental_model

Kinetic, inhibition and recombinant-enzyme pathway mapping

exposure

Therapeutically relevant substrate concentrations

limitations

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

nutrient_topic

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

organism

Human liver microsomes and expressed CYPs

plain_language

The key activation step cannot be replaced by the statement that CYP1A2 is induced.

primary_references

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

tissue_or_cell_type

Sequential tamoxifen metabolism

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1000–1011

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

### dim-tamoxifen-endoxifen Conversion of N-desmethyltamoxifen to endoxifen was catalyzed by CYP2D6 in the tested system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The key activation step cannot be replaced by the statement that CYP1A2 is induced. organism: Human liver microsomes and expressed CYPs tissue_or_cell_type: Sequential tamoxifen metabolism experimental_model: Kinetic, inhibition and recombinant-enzyme pathway mapping limitations: Biochemical pathway identity; does not attribute the observed DIM interaction to any single CYP or prove clinical cancer outcomes. exposure: Therapeutically relevant substrate concentrations evidence_span: {"source_cache": "artifacts/dim-research/15159443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081", "start_char": 0, "end_char": 1544, "text_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081"} [dim-p15159443] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. (2004). https://pubmed.ncbi.nlm.nih.gov/15159443/ DOI: 10.1124/jpet.104.065607

evidence_span

{"source_cache": "artifacts/berberine-research/39488825.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33", "start_char": 0, "end_char": 1787, "text_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33"}

experimental_model

Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics

exposure

Oral berberine; OCT1 and CYP2D6 functional variants; sex-stratified analysis

limitations

Human OCT1 null finding differs from cellular and mouse findings. Sex-specific CYP2D6 result is not a universal rule for all formulations or a dosing algorithm.

nutrient_topic

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

organism

Human participants and human OCT1; Oct1/2-deficient mice in separate arms

plain_language

The metabolic effect of this gene variant depended on sex in this study.

primary_references

[berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454

tissue_or_cell_type

Liver transport and systemic exposure

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 272–283

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics · source_derived_draft · unverified_draft

### berberine-cyp2d6-sex Female CYP2D6 poor metabolizers had an 80% lower M1-to-berberine ratio; the genotype effect was not found in males. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The metabolic effect of this gene variant depended on sex in this study. organism: Human participants and human OCT1; Oct1/2-deficient mice in separate arms tissue_or_cell_type: Liver transport and systemic exposure experimental_model: Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics limitations: Human OCT1 null finding differs from cellular and mouse findings. Sex-specific CYP2D6 result is not a universal rule for all formulations or a dosing algorithm. exposure: Oral berberine; OCT1 and CYP2D6 functional variants; sex-stratified analysis evidence_span: {"source_cache": "artifacts/berberine-research/39488825.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33", "start_char": 0, "end_char": 1787, "text_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33"} [berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454

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 809–820

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-cyp2d6-activity Mangiferin reduced measured CYP2D6 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

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 422–428

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-cyp2d6 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 CYP2D6 phenotypic activity using dextromethorphan 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_access

Primary abstract

experimental_model

Enzyme activity assay.

limitations

High in-vitro concentration; no human clearance change established.

nutrient_topic

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

plain_language

Different CYP enzymes have different measured sensitivities.

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 228–234

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Enzyme activity assay. · source_derived_draft · unverified_draft

## myricetin-cyp2d6 Different CYP enzymes have different measured sensitivities. Myricetin inhibited CYP2D6 in the tested enzyme assay, IC50 57 micromolar. Model: Enzyme activity assay. Limitations: High in-vitro concentration; no human clearance change established. 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

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 410–417

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-cyp2d6 A negative enzyme-interaction result is retained. SAC showed little effect on tested human CYP2D6 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"}

acting_entity

n-acetyl-s-allylcysteine

dose

SAC 0.01–1 mM; N-acetyl-SAC 1 mM

duration

Probe-specific incubation

evidence_access

Primary full-text HTML, abstract/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

Small in-vitro effect; no patient interaction magnitude.

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 metabolite differed from the parent.

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 428–435

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-nac-cyp2d6 A metabolite differed from the parent. N-acetyl-SAC inhibited the CYP2D6 probe reaction by 19% at 1 mM. Model: Pooled human liver microsomes; probe substrate metabolism Limitations: Small in-vitro effect; no patient interaction magnitude. Evidence access: Primary full-text HTML, abstract/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": "n-acetyl-s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

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

{"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"}

experimental_model

Two-phase randomized crossover enzyme-phenotyping study

exposure

Berberine 300 mg three times daily for 14 days versus placebo

limitations

Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence.

nutrient_topic

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

organism

Healthy human male volunteers; 17 completed

plain_language

A human probe study measured slower metabolism through CYP2D6.

primary_references

[berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2

tissue_or_cell_type

Oral probe pharmacokinetics and urinary metabolite ratios

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 636–647

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-phase randomized crossover enzyme-phenotyping study · source_derived_draft · unverified_draft

### berberine-human-cyp-2d6 Berberine increased the urinary dextromethorphan/dextrorphan ratio approximately ninefold, indicating reduced CYP2D6 activity. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A human probe study measured slower metabolism through CYP2D6. organism: Healthy human male volunteers; 17 completed tissue_or_cell_type: Oral probe pharmacokinetics and urinary metabolite ratios experimental_model: Two-phase randomized crossover enzyme-phenotyping study limitations: Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence. exposure: Berberine 300 mg three times daily for 14 days versus placebo evidence_span: {"source_cache": "artifacts/berberine-research/21870106.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5", "start_char": 0, "end_char": 1817, "text_sha256": "12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5"} [berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2

dose

Red wine, IPA, blonde beer or non-alcoholic beer

duration

Single-dose crossover

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

Twenty healthy adults in a randomized crossover trial

limitations

Alcohol and beverage constituents are co-exposures; the study does not justify alcohol consumption for hydroxytyrosol production.

nutrient_topic

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

organism

Twenty healthy adults in a randomized crossover trial

plain_language

After beer or red wine in 20 adults, urinary recovery supported tyrosol-to-hydroxytyrosol conversion, and the conversion ratio tracked CYP2A6/CYP2D6 activity score, sex and beverage matrix.

primary_references

Generation of the Antioxidant Hydroxytyrosol from Tyrosol Present in Beer and Red Wine in a Randomized Clinical Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31540384/ DOI: 10.3390/nu11092241

route

Oral beverage

tissue

Tyrosol and hydroxytyrosol recovery with genotype score

Hydroxytyrosol: mechanism of action and interactions (2026-09-20) · lines 55–64

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Twenty healthy adults in a randomized crossover trial · source_derived_draft · unverified_draft

## hydroxytyrosol-human-tyrosol-conversion After beer or red wine in 20 adults, urinary recovery supported tyrosol-to-hydroxytyrosol conversion, and the conversion ratio tracked CYP2A6/CYP2D6 activity score, sex and beverage matrix. Model/species: Twenty healthy adults in a randomized crossover trial Tissue/system: Tyrosol and hydroxytyrosol recovery with genotype score Exposure: Red wine, IPA, blonde beer or non-alcoholic beer Route: Oral beverage Duration: Single-dose crossover Limits: Alcohol and beverage constituents are co-exposures; the study does not justify alcohol consumption for hydroxytyrosol production. Primary reference: Generation of the Antioxidant Hydroxytyrosol from Tyrosol Present in Beer and Red Wine in a Randomized Clinical Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31540384/ DOI: 10.3390/nu11092241 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

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.