Nutrient chapter

Resveratrol

Context-specific entity; species, compartment and exposure are stated on each claim.

72 recorded mechanisms · 9 availability situations · 6 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

In six volunteers given 25 mg radiolabeled oral resveratrol, estimated absorption was at least 70%.
Resveratrol → Human oral resveratrol absorption source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human oral/IV radiotracer study.
limitations
The approximately 2 micromolar peak represented parent plus metabolites, not free resveratrol.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Absorption does not mean most of the dose circulates unchanged.
primary_references
High absorption but very low bioavailability of oral resveratrol in humans. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15333514/ · DOI 10.1124/dmd.104.000885
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 14–20
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human oral/IV radiotracer study. · source_derived_draft · unverified_draft
## resveratrol-human-absorption Absorption does not mean most of the dose circulates unchanged. In six volunteers given 25 mg radiolabeled oral resveratrol, estimated absorption was at least 70%. Model: Human oral/IV radiotracer study. Limitations: The approximately 2 micromolar peak represented parent plus metabolites, not free resveratrol. Evidence access: Primary abstract High absorption but very low bioavailability of oral resveratrol in humans. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15333514/ · DOI 10.1124/dmd.104.000885
Complete structured claim and evidence
After the 25 mg oral dose in six volunteers, unchanged resveratrol in plasma was below 5 ng/mL despite substantial absorption.
Resveratrol → Human plasma unconjugated resveratrol concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human radiotracer study; single dose.
limitations
Not a universal exposure ceiling across formulations or doses.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Rapid metabolism limits circulating parent compound.
primary_references
High absorption but very low bioavailability of oral resveratrol in humans. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15333514/ · DOI 10.1124/dmd.104.000885
trigger_kind
biomarker_context Imported condition classification; unverified.
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 22–28
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human radiotracer study; single dose. · source_derived_draft · unverified_draft
## resveratrol-human-free-exposure Rapid metabolism limits circulating parent compound. After the 25 mg oral dose in six volunteers, unchanged resveratrol in plasma was below 5 ng/mL despite substantial absorption. Model: Human radiotracer study; single dose. Limitations: Not a universal exposure ceiling across formulations or doses. Evidence access: Primary abstract High absorption but very low bioavailability of oral resveratrol in humans. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15333514/ · DOI 10.1124/dmd.104.000885
Complete structured claim and evidence
Human UGT1A1 predominantly formed the 3-O glucuronide of trans-resveratrol in microsomal/recombinant experiments; reported Km was 149 micromolar.
Human UDP-glucuronosyltransferase 1A1 / UGT1A1 → Resveratrol 3-O-glucuronide source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human liver/intestine microsomes and recombinant UGTs.
limitations
Predominant contribution is not exclusive specificity; Km is not a human plasma target.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
An independently named enzyme produces an independently named metabolite.
primary_references
Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16597364/ · DOI 10.1211/jpp.58.4.0006
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 30–36
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human liver/intestine microsomes and recombinant UGTs. · source_derived_draft · unverified_draft
## resveratrol-ugt1a1 An independently named enzyme produces an independently named metabolite. Human UGT1A1 predominantly formed the 3-O glucuronide of trans-resveratrol in microsomal/recombinant experiments; reported Km was 149 micromolar. Model: Human liver/intestine microsomes and recombinant UGTs. Limitations: Predominant contribution is not exclusive specificity; Km is not a human plasma target. Evidence access: Primary abstract Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16597364/ · DOI 10.1211/jpp.58.4.0006
Complete structured claim and evidence
Human UGT1A9 predominantly formed the 4′-O glucuronide of trans-resveratrol in microsomal/recombinant experiments; reported Km was 365 micromolar.
Human UDP-glucuronosyltransferase 1A9 / UGT1A9 → Resveratrol 4′-O-glucuronide source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human liver/intestine microsomes and recombinant UGTs.
limitations
Predominant contribution is not exclusive specificity; Km is not a human plasma target.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
An independently named enzyme produces an independently named metabolite.
primary_references
Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16597364/ · DOI 10.1211/jpp.58.4.0006
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 38–44
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human liver/intestine microsomes and recombinant UGTs. · source_derived_draft · unverified_draft
## resveratrol-ugt1a9 An independently named enzyme produces an independently named metabolite. Human UGT1A9 predominantly formed the 4′-O glucuronide of trans-resveratrol in microsomal/recombinant experiments; reported Km was 365 micromolar. Model: Human liver/intestine microsomes and recombinant UGTs. Limitations: Predominant contribution is not exclusive specificity; Km is not a human plasma target. Evidence access: Primary abstract Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16597364/ · DOI 10.1211/jpp.58.4.0006
Complete structured claim and evidence
Trans-resveratrol inhibited SN-38 glucuronidation in human enzyme experiments (Ki 6.2 ± 2.1 micromolar), while bilirubin glucuronidation showed no major change.
trans-Resveratrol → SN-38 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human microsomal/recombinant assays.
limitations
Not demonstrated irinotecan toxicity or a clinical dose-adjustment rule.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
The interaction depends on the enzyme substrate.
primary_references
Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16597364/ · DOI 10.1211/jpp.58.4.0006
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 46–52
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human microsomal/recombinant assays. · source_derived_draft · unverified_draft
## resveratrol-ugt-substrate-selectivity The interaction depends on the enzyme substrate. Trans-resveratrol inhibited SN-38 glucuronidation in human enzyme experiments (Ki 6.2 ± 2.1 micromolar), while bilirubin glucuronidation showed no major change. Model: Human microsomal/recombinant assays. Limitations: Not demonstrated irinotecan toxicity or a clinical dose-adjustment rule. Evidence access: Primary abstract Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16597364/ · DOI 10.1211/jpp.58.4.0006
Complete structured claim and evidence
Human fecal fermentation and urine analyses identified Dihydroresveratrol among trans-resveratrol-derived microbial metabolites.
trans-Resveratrol → Dihydroresveratrol source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Seven fecal donors; separate 12-person intervention using grapevine-shoot supplement at 0.5 mg/kg.
limitations
Metabolite patterns varied by person; a mixed supplement is not a purified-compound clinical efficacy test.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Gut microbes change which molecules reach the body.
primary_references
In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23283496/ · DOI 10.3945/ajcn.112.049379
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 54–60
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Seven fecal donors; separate 12-person intervention using grapevine-shoot supplement at 0.5 mg/kg. · source_derived_draft · unverified_draft
## resveratrol-microbial-hydrogenation Gut microbes change which molecules reach the body. Human fecal fermentation and urine analyses identified Dihydroresveratrol among trans-resveratrol-derived microbial metabolites. Model: Seven fecal donors; separate 12-person intervention using grapevine-shoot supplement at 0.5 mg/kg. Limitations: Metabolite patterns varied by person; a mixed supplement is not a purified-compound clinical efficacy test. Evidence access: Primary abstract In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23283496/ · DOI 10.3945/ajcn.112.049379
Complete structured claim and evidence
Human fecal fermentation and urine analyses identified 3,4′-Dihydroxy-trans-stilbene among trans-resveratrol-derived microbial metabolites.
trans-Resveratrol → 3,4′-Dihydroxy-trans-stilbene source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Seven fecal donors; separate 12-person intervention using grapevine-shoot supplement at 0.5 mg/kg.
limitations
Metabolite patterns varied by person; a mixed supplement is not a purified-compound clinical efficacy test.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Gut microbes change which molecules reach the body.
primary_references
In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23283496/ · DOI 10.3945/ajcn.112.049379
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 62–68
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Seven fecal donors; separate 12-person intervention using grapevine-shoot supplement at 0.5 mg/kg. · source_derived_draft · unverified_draft
## resveratrol-microbial-dehydroxylation Gut microbes change which molecules reach the body. Human fecal fermentation and urine analyses identified 3,4′-Dihydroxy-trans-stilbene among trans-resveratrol-derived microbial metabolites. Model: Seven fecal donors; separate 12-person intervention using grapevine-shoot supplement at 0.5 mg/kg. Limitations: Metabolite patterns varied by person; a mixed supplement is not a purified-compound clinical efficacy test. Evidence access: Primary abstract In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23283496/ · DOI 10.3945/ajcn.112.049379
Complete structured claim and evidence
Human fecal fermentation and urine analyses identified Lunularin among trans-resveratrol-derived microbial metabolites.
trans-Resveratrol → Lunularin source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Seven fecal donors; separate 12-person intervention using grapevine-shoot supplement at 0.5 mg/kg.
limitations
Metabolite patterns varied by person; a mixed supplement is not a purified-compound clinical efficacy test.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Gut microbes change which molecules reach the body.
primary_references
In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23283496/ · DOI 10.3945/ajcn.112.049379
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 70–76
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Seven fecal donors; separate 12-person intervention using grapevine-shoot supplement at 0.5 mg/kg. · source_derived_draft · unverified_draft
## resveratrol-microbial-lunularin Gut microbes change which molecules reach the body. Human fecal fermentation and urine analyses identified Lunularin among trans-resveratrol-derived microbial metabolites. Model: Seven fecal donors; separate 12-person intervention using grapevine-shoot supplement at 0.5 mg/kg. Limitations: Metabolite patterns varied by person; a mixed supplement is not a purified-compound clinical efficacy test. Evidence access: Primary abstract In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23283496/ · DOI 10.3945/ajcn.112.049379
Complete structured claim and evidence
A tested Slackia equolifaciens strain converted trans-resveratrol to dihydroresveratrol in pure culture.
Slackia equolifaciens → Dihydroresveratrol source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Selected human fecal bacterial strains.
limitations
Do not assign the unidentified dehydroxylation reactions to this strain.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A specific microbial producer is preserved as its own node.
primary_references
In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23283496/ · DOI 10.3945/ajcn.112.049379
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 78–84
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Selected human fecal bacterial strains. · source_derived_draft · unverified_draft
## resveratrol-slackia-equolifaciens A specific microbial producer is preserved as its own node. A tested Slackia equolifaciens strain converted trans-resveratrol to dihydroresveratrol in pure culture. Model: Selected human fecal bacterial strains. Limitations: Do not assign the unidentified dehydroxylation reactions to this strain. Evidence access: Primary abstract In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23283496/ · DOI 10.3945/ajcn.112.049379
Complete structured claim and evidence
A tested Adlercreutzia equolifaciens strain converted trans-resveratrol to dihydroresveratrol in pure culture.
Adlercreutzia equolifaciens → Dihydroresveratrol source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Selected human fecal bacterial strains.
limitations
Do not assign the unidentified dehydroxylation reactions to this strain.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A specific microbial producer is preserved as its own node.
primary_references
In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23283496/ · DOI 10.3945/ajcn.112.049379
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 86–92
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Selected human fecal bacterial strains. · source_derived_draft · unverified_draft
## resveratrol-adlercreutzia-equolifaciens A specific microbial producer is preserved as its own node. A tested Adlercreutzia equolifaciens strain converted trans-resveratrol to dihydroresveratrol in pure culture. Model: Selected human fecal bacterial strains. Limitations: Do not assign the unidentified dehydroxylation reactions to this strain. Evidence access: Primary abstract In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23283496/ · DOI 10.3945/ajcn.112.049379
Complete structured claim and evidence
Resveratrol monosulfates were converted to parent resveratrol in human colorectal cells; sulfate hydrolysis also liberated parent after metabolite dosing in mice.
Resveratrol 3-O-sulfate → Resveratrol source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human cell experiments, human exposure measurements and separate mouse pharmacokinetics.
limitations
Cell uptake was transporter-dependent; abstract does not identify all responsible transporter/isoenzyme identities.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Conjugation can create a reservoir, not simply inactivate everything.
primary_references
Sulfate metabolites provide an intracellular pool for resveratrol generation and induce autophagy with senescence. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24089405/ · DOI 10.1126/scitranslmed.3005870
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 94–100
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell experiments, human exposure measurements and separate mouse pharmacokinetics. · source_derived_draft · unverified_draft
## resveratrol-sulfate-reservoir Conjugation can create a reservoir, not simply inactivate everything. Resveratrol monosulfates were converted to parent resveratrol in human colorectal cells; sulfate hydrolysis also liberated parent after metabolite dosing in mice. Model: Human cell experiments, human exposure measurements and separate mouse pharmacokinetics. Limitations: Cell uptake was transporter-dependent; abstract does not identify all responsible transporter/isoenzyme identities. Evidence access: Primary abstract Sulfate metabolites provide an intracellular pool for resveratrol generation and induce autophagy with senescence. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24089405/ · DOI 10.1126/scitranslmed.3005870
Complete structured claim and evidence
Adding a sulfatase inhibitor reduced intracellular resveratrol and abrogated monosulfate-induced autophagy and senescence in human colorectal cancer cells.
Resveratrol sulfate hydrolysis in human colorectal cells → Autophagy and senescence after resveratrol sulfates in human colorectal cancer cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human colorectal cancer cultures.
limitations
Senescence induction is not senolytic removal; not established prevention or treatment in people.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Blocking local release weakened the cell response.
primary_references
Sulfate metabolites provide an intracellular pool for resveratrol generation and induce autophagy with senescence. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24089405/ · DOI 10.1126/scitranslmed.3005870
trigger_kind
machinery_impairment Imported condition classification; unverified.
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 102–108
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human colorectal cancer cultures. · source_derived_draft · unverified_draft
## resveratrol-sulfatase-block Blocking local release weakened the cell response. Adding a sulfatase inhibitor reduced intracellular resveratrol and abrogated monosulfate-induced autophagy and senescence in human colorectal cancer cells. Model: Human colorectal cancer cultures. Limitations: Senescence induction is not senolytic removal; not established prevention or treatment in people. Evidence access: Primary abstract Sulfate metabolites provide an intracellular pool for resveratrol generation and induce autophagy with senescence. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24089405/ · DOI 10.1126/scitranslmed.3005870
Complete structured claim and evidence
Resveratrol bound the active-site cleft of human NQO2 beside FAD, with reported dissociation constant 35 nM, and inhibited activity in vitro.
Resveratrol → Human quinone reductase 2 / NQO2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified enzyme crystal structure and biochemical assays.
limitations
Binding beside FAD does not mean resveratrol depletes riboflavin or displaces FAD.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A riboflavin-derived cofactor sits beside a directly observed binding site.
primary_references
Crystal structure of quinone reductase 2 in complex with resveratrol. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15350128/ · DOI 10.1021/bi049162o
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 110–116
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified enzyme crystal structure and biochemical assays. · source_derived_draft · unverified_draft
## resveratrol-nqo2-binding A riboflavin-derived cofactor sits beside a directly observed binding site. Resveratrol bound the active-site cleft of human NQO2 beside FAD, with reported dissociation constant 35 nM, and inhibited activity in vitro. Model: Purified enzyme crystal structure and biochemical assays. Limitations: Binding beside FAD does not mean resveratrol depletes riboflavin or displaces FAD. Evidence access: Primary abstract Crystal structure of quinone reductase 2 in complex with resveratrol. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15350128/ · DOI 10.1021/bi049162o
Complete structured claim and evidence
NQO2 RNAi in human K562 cells increased quinone resistance and antioxidant/detoxification enzyme expression, resembling resveratrol treatment.
Human quinone reductase 2 / NQO2 → Quinone resistance in human K562 cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human leukemia cell culture.
limitations
Phenocopy does not establish that all resveratrol effects are mediated by NQO2.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Genetic reduction of a shared melatonin target reproduced part of the response.
primary_references
Crystal structure of quinone reductase 2 in complex with resveratrol. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15350128/ · DOI 10.1021/bi049162o
trigger_kind
machinery_impairment Imported condition classification; unverified.
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 118–124
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human leukemia cell culture. · source_derived_draft · unverified_draft
## resveratrol-nqo2-loss Genetic reduction of a shared melatonin target reproduced part of the response. NQO2 RNAi in human K562 cells increased quinone resistance and antioxidant/detoxification enzyme expression, resembling resveratrol treatment. Model: Human leukemia cell culture. Limitations: Phenocopy does not establish that all resveratrol effects are mediated by NQO2. Evidence access: Primary abstract Crystal structure of quinone reductase 2 in complex with resveratrol. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15350128/ · DOI 10.1021/bi049162o
Complete structured claim and evidence
Resveratrol-3-sulfate associated with the soluble human mitoNEET domain in mass-spectrometry and calorimetry experiments, with fitted dissociation constants approximately 5–16 micromolar.
Resveratrol 3-O-sulfate → Human mitoNEET / CISD1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified soluble cytosolic domain, residues 32–108.
limitations
Association does not demonstrate altered iron-sulfur transfer or clinical mitochondrial benefit.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
The sulfate metabolite has a target the parent did not share.
primary_references
Complexes of the outer mitochondrial membrane protein mitoNEET with resveratrol-3-sulfate. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21591687/ · DOI 10.1021/bi200546s
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 126–132
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified soluble cytosolic domain, residues 32–108. · source_derived_draft · unverified_draft
## resveratrol-mitoneet-metabolite The sulfate metabolite has a target the parent did not share. Resveratrol-3-sulfate associated with the soluble human mitoNEET domain in mass-spectrometry and calorimetry experiments, with fitted dissociation constants approximately 5–16 micromolar. Model: Purified soluble cytosolic domain, residues 32–108. Limitations: Association does not demonstrate altered iron-sulfur transfer or clinical mitochondrial benefit. Evidence access: Primary full text Complexes of the outer mitochondrial membrane protein mitoNEET with resveratrol-3-sulfate. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21591687/ · DOI 10.1021/bi200546s
Complete structured claim and evidence
Parent resveratrol showed no tendency to interact with mitoNEET in the reported binding experiments.
Resveratrol → Human mitoNEET / CISD1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same purified protein study.
limitations
Null applies to the tested conditions.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Do not transfer a metabolite target to the parent.
primary_references
Complexes of the outer mitochondrial membrane protein mitoNEET with resveratrol-3-sulfate. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21591687/ · DOI 10.1021/bi200546s
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 134–140
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same purified protein study. · source_derived_draft · unverified_draft
## resveratrol-mitoneet-parent-null Do not transfer a metabolite target to the parent. Parent resveratrol showed no tendency to interact with mitoNEET in the reported binding experiments. Model: Same purified protein study. Limitations: Null applies to the tested conditions. Evidence access: Primary abstract Complexes of the outer mitochondrial membrane protein mitoNEET with resveratrol-3-sulfate. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21591687/ · DOI 10.1021/bi200546s
Complete structured claim and evidence
The bovine F1-ATPase crystal structure placed resveratrol in a pocket between the gamma tip and beta-TP subunit at the rotary bearing.
Resveratrol → Bovine mitochondrial F1-ATPase source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Isolated bovine heart F1 structures and inhibition study.
limitations
The proposed block of rotation explains inhibition; the structure does not establish human tissue ATP loss after oral intake.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Binding can obstruct the rotary machinery for energy conversion.
primary_references
Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17698806/ · DOI 10.1073/pnas.0706290104
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 142–148
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated bovine heart F1 structures and inhibition study. · source_derived_draft · unverified_draft
## resveratrol-f1-binding Binding can obstruct the rotary machinery for energy conversion. The bovine F1-ATPase crystal structure placed resveratrol in a pocket between the gamma tip and beta-TP subunit at the rotary bearing. Model: Isolated bovine heart F1 structures and inhibition study. Limitations: The proposed block of rotation explains inhibition; the structure does not establish human tissue ATP loss after oral intake. Evidence access: Primary abstract Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17698806/ · DOI 10.1073/pnas.0706290104
Complete structured claim and evidence
Resveratrol did not activate human SIRT1 on the tested unlabelled p53 peptide or full-length p53 and acetyl-CoA-synthetase substrates, while fluorophore-tagged peptide assays showed activation.
Resveratrol → SIRT1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Biochemical comparison of labelled and native substrates.
limitations
This is a negative result for tested substrates, not proof that no native sequence can respond.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Some original activation assays depended on the artificial reporter.
primary_references
SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20061378/ · DOI 10.1074/jbc.M109.088682
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biochemical comparison of labelled and native substrates. · source_derived_draft · unverified_draft
## resveratrol-sirt1-native-null Some original activation assays depended on the artificial reporter. Resveratrol did not activate human SIRT1 on the tested unlabelled p53 peptide or full-length p53 and acetyl-CoA-synthetase substrates, while fluorophore-tagged peptide assays showed activation. Model: Biochemical comparison of labelled and native substrates. Limitations: This is a negative result for tested substrates, not proof that no native sequence can respond. Evidence access: Primary abstract SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20061378/ · DOI 10.1074/jbc.M109.088682
Complete structured claim and evidence
In a 6,802-site physiological acetyl-peptide screen, resveratrol stimulated SIRT1 deacetylation of a small subset, inhibited another subset and left most sites largely unchanged; solution assays confirmed selected categories.
Resveratrol → SIRT1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Peptide arrays and solution enzyme assays.
limitations
Peptides do not reproduce complete chromatin or whole-cell substrate competition.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
SIRT1 is not a universal on/off switch for resveratrol.
primary_references
Sirt1 activation by resveratrol is substrate sequence-selective. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23524286/ · DOI 10.18632/aging.100542
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Peptide arrays and solution enzyme assays. · source_derived_draft · unverified_draft
## resveratrol-sirt1-sequence-selectivity SIRT1 is not a universal on/off switch for resveratrol. In a 6,802-site physiological acetyl-peptide screen, resveratrol stimulated SIRT1 deacetylation of a small subset, inhibited another subset and left most sites largely unchanged; solution assays confirmed selected categories. Model: Peptide arrays and solution enzyme assays. Limitations: Peptides do not reproduce complete chromatin or whole-cell substrate competition. Evidence access: Primary full text Sirt1 activation by resveratrol is substrate sequence-selective. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23524286/ · DOI 10.18632/aging.100542
Complete structured claim and evidence
The E230K substitution attenuated resveratrol activation of human SIRT1 with an AMC substrate and a natural-amino-acid substrate without abolishing basal catalytic activity.
Human SIRT1 E230K activation-defective variant → SIRT1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Recombinant mutagenesis; 40 micromolar resveratrol in the illustrated AMC assay.
limitations
Other figures use synthetic STACs; those interventions are not silently attributed to resveratrol.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
An enzyme residue contributes to selective activation.
primary_references
Evidence for a common mechanism of SIRT1 regulation by allosteric activators. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23471411/ · DOI 10.1126/science.1231097
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant mutagenesis; 40 micromolar resveratrol in the illustrated AMC assay. · source_derived_draft · unverified_draft
## resveratrol-sirt1-e230 An enzyme residue contributes to selective activation. The E230K substitution attenuated resveratrol activation of human SIRT1 with an AMC substrate and a natural-amino-acid substrate without abolishing basal catalytic activity. Model: Recombinant mutagenesis; 40 micromolar resveratrol in the illustrated AMC assay. Limitations: Other figures use synthetic STACs; those interventions are not silently attributed to resveratrol. Evidence access: Primary full text Evidence for a common mechanism of SIRT1 regulation by allosteric activators. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23471411/ · DOI 10.1126/science.1231097
Complete structured claim and evidence
Adult-induced Sirt1 deletion prevented resveratrol-associated improvements in mouse skeletal-muscle mitochondrial function at both tested dietary doses.
Mouse sirtuin 1 / Sirt1 → Resveratrol-associated mouse muscle mitochondrial improvement source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
High-fat-fed mice receiving approximately 25–30 or 215–230 mg/kg/day.
limitations
Adult knockout, tissue context and high-fat diet matter; not a human niacin-deficiency experiment.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A response can require intact machinery even if upstream signals still change.
primary_references
SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560220/ · DOI 10.1016/j.cmet.2012.04.003
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · High-fat-fed mice receiving approximately 25–30 or 215–230 mg/kg/day. · source_derived_draft · unverified_draft
## resveratrol-mouse-sirt1-loss A response can require intact machinery even if upstream signals still change. Adult-induced Sirt1 deletion prevented resveratrol-associated improvements in mouse skeletal-muscle mitochondrial function at both tested dietary doses. Model: High-fat-fed mice receiving approximately 25–30 or 215–230 mg/kg/day. Limitations: Adult knockout, tissue context and high-fat diet matter; not a human niacin-deficiency experiment. Evidence access: Primary full text SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560220/ · DOI 10.1016/j.cmet.2012.04.003
Complete structured claim and evidence
In mouse C2C12 cells, 25 micromolar resveratrol activated AMPK in a Sirt1-dependent manner; at 50 micromolar, activation could occur independently of Sirt1.
Resveratrol → Mouse AMPK complexes source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse muscle-cell dose comparison.
limitations
Neither concentration is a demonstrated human muscle exposure.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
The route to the same signaling node changes with exposure.
primary_references
SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560220/ · DOI 10.1016/j.cmet.2012.04.003
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse muscle-cell dose comparison. · source_derived_draft · unverified_draft
## resveratrol-mouse-ampk-dose The route to the same signaling node changes with exposure. In mouse C2C12 cells, 25 micromolar resveratrol activated AMPK in a Sirt1-dependent manner; at 50 micromolar, activation could occur independently of Sirt1. Model: Mouse muscle-cell dose comparison. Limitations: Neither concentration is a demonstrated human muscle exposure. Evidence access: Primary full text SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560220/ · DOI 10.1016/j.cmet.2012.04.003
Complete structured claim and evidence
In mouse C2C12 cells, 25 micromolar resveratrol increased ATP at later time points, while 50 micromolar reduced ATP and mitochondrial membrane potential.
Resveratrol → ATP content in mouse C2C12 cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Dose and time-course experiments.
limitations
Context difference is recorded directly, not labelled an unexplained contradiction.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
AMPK activation can accompany energy stress rather than improved energy supply.
primary_references
SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560220/ · DOI 10.1016/j.cmet.2012.04.003
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Dose and time-course experiments. · source_derived_draft · unverified_draft
## resveratrol-mouse-atp-dose AMPK activation can accompany energy stress rather than improved energy supply. In mouse C2C12 cells, 25 micromolar resveratrol increased ATP at later time points, while 50 micromolar reduced ATP and mitochondrial membrane potential. Model: Dose and time-course experiments. Limitations: Context difference is recorded directly, not labelled an unexplained contradiction. Evidence access: Primary full text SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560220/ · DOI 10.1016/j.cmet.2012.04.003
Complete structured claim and evidence
Resveratrol increased cAMP in mouse C2C12 myotubes at concentrations up to 50 micromolar; oral gavage also increased measured muscle and adipose cAMP in mice.
Resveratrol → Cyclic AMP content in mouse C2C12 cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse cells and separate mouse tissue measurements.
limitations
A changed pool does not by itself identify its synthesis or breakdown rate.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Reduced signal breakdown connects enzyme inhibition to cellular signaling.
primary_references
Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse cells and separate mouse tissue measurements. · source_derived_draft · unverified_draft
## resveratrol-mouse-camp Reduced signal breakdown connects enzyme inhibition to cellular signaling. Resveratrol increased cAMP in mouse C2C12 myotubes at concentrations up to 50 micromolar; oral gavage also increased measured muscle and adipose cAMP in mice. Model: Mouse cells and separate mouse tissue measurements. Limitations: A changed pool does not by itself identify its synthesis or breakdown rate. Evidence access: Primary full text Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
Complete structured claim and evidence
Resveratrol inhibited the tested recombinant PDE1 preparation with approximate IC50 6 micromolar.
Resveratrol → Recombinant PDE1 preparation in Park 2012 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Cell-free cyclic-nucleotide hydrolysis assay.
limitations
Retains preparation identity: do not infer an unreported isoform/species or a human effective dose.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Slower cAMP breakdown can extend a signaling pulse.
primary_references
Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free cyclic-nucleotide hydrolysis assay. · source_derived_draft · unverified_draft
## resveratrol-pde1 Slower cAMP breakdown can extend a signaling pulse. Resveratrol inhibited the tested recombinant PDE1 preparation with approximate IC50 6 micromolar. Model: Cell-free cyclic-nucleotide hydrolysis assay. Limitations: Retains preparation identity: do not infer an unreported isoform/species or a human effective dose. Evidence access: Primary full text Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
Complete structured claim and evidence
Resveratrol inhibited the tested recombinant PDE3 preparation with approximate IC50 10 micromolar.
Resveratrol → Recombinant PDE3 preparation in Park 2012 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Cell-free cyclic-nucleotide hydrolysis assay.
limitations
Retains preparation identity: do not infer an unreported isoform/species or a human effective dose.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Slower cAMP breakdown can extend a signaling pulse.
primary_references
Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free cyclic-nucleotide hydrolysis assay. · source_derived_draft · unverified_draft
## resveratrol-pde3 Slower cAMP breakdown can extend a signaling pulse. Resveratrol inhibited the tested recombinant PDE3 preparation with approximate IC50 10 micromolar. Model: Cell-free cyclic-nucleotide hydrolysis assay. Limitations: Retains preparation identity: do not infer an unreported isoform/species or a human effective dose. Evidence access: Primary full text Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
Complete structured claim and evidence
Resveratrol inhibited the tested recombinant PDE4 preparation with approximate IC50 14 micromolar.
Resveratrol → Recombinant PDE4 preparation in Park 2012 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Cell-free cyclic-nucleotide hydrolysis assay.
limitations
Retains preparation identity: do not infer an unreported isoform/species or a human effective dose.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Slower cAMP breakdown can extend a signaling pulse.
primary_references
Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free cyclic-nucleotide hydrolysis assay. · source_derived_draft · unverified_draft
## resveratrol-pde4 Slower cAMP breakdown can extend a signaling pulse. Resveratrol inhibited the tested recombinant PDE4 preparation with approximate IC50 14 micromolar. Model: Cell-free cyclic-nucleotide hydrolysis assay. Limitations: Retains preparation identity: do not infer an unreported isoform/species or a human effective dose. Evidence access: Primary full text Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
Complete structured claim and evidence
Resveratrol did not inhibit tested PDE2 or PDE5 activity in the same recombinant panel.
Resveratrol → PDE2/PDE5 activity in Park 2012 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Cell-free comparison.
limitations
Not a general inhibitor of every cyclic-nucleotide phosphodiesterase.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
The PDE effect is selective within the tested panel.
primary_references
Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free comparison. · source_derived_draft · unverified_draft
## resveratrol-pde-selectivity The PDE effect is selective within the tested panel. Resveratrol did not inhibit tested PDE2 or PDE5 activity in the same recombinant panel. Model: Cell-free comparison. Limitations: Not a general inhibitor of every cyclic-nucleotide phosphodiesterase. Evidence access: Primary full text Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
Complete structured claim and evidence
Epac1 siRNA, unlike PKA catalytic-subunit siRNA, blocked resveratrol-induced AMPK/ACC phosphorylation in human HeLa cells.
Human Epac1 / RAPGEF3 → Resveratrol-associated AMPK activation in HeLa cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
HeLa experiments selected to avoid myogenesis confounding; 50 micromolar resveratrol.
limitations
RNAi does not make all tissue responses Epac1-dependent.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A cAMP effector is a tested dependency.
primary_references
Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HeLa experiments selected to avoid myogenesis confounding; 50 micromolar resveratrol. · source_derived_draft · unverified_draft
## resveratrol-epac-loss A cAMP effector is a tested dependency. Epac1 siRNA, unlike PKA catalytic-subunit siRNA, blocked resveratrol-induced AMPK/ACC phosphorylation in human HeLa cells. Model: HeLa experiments selected to avoid myogenesis confounding; 50 micromolar resveratrol. Limitations: RNAi does not make all tissue responses Epac1-dependent. Evidence access: Primary full text Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
Complete structured claim and evidence
Epac1 siRNA prevented the resveratrol-induced NAD increase and PGC-1alpha deacetylation in human HeLa experiments.
Human Epac1 / RAPGEF3 → Resveratrol-associated NAD increase in HeLa cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Same cellular mechanism study.
limitations
NAD measurement and substrate deacetylation do not establish direct SIRT1 binding.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Calcium/cAMP signaling connects to NAD-dependent regulation.
primary_references
Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same cellular mechanism study. · source_derived_draft · unverified_draft
## resveratrol-epac-nad-loss Calcium/cAMP signaling connects to NAD-dependent regulation. Epac1 siRNA prevented the resveratrol-induced NAD increase and PGC-1alpha deacetylation in human HeLa experiments. Model: Same cellular mechanism study. Limitations: NAD measurement and substrate deacetylation do not establish direct SIRT1 binding. Evidence access: Primary full text Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
Complete structured claim and evidence
Intracellular calcium chelation with BAPTA-AM reduced AMPK and ACC phosphorylation induced by 50 micromolar resveratrol in mouse C2C12 myotubes.
BAPTA-AM intracellular calcium chelator → Mouse AMPK complexes source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Pharmacological intracellular calcium buffering.
limitations
This is not a dietary calcium-deficiency threshold.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Removing available signaling calcium weakened the response.
primary_references
Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pharmacological intracellular calcium buffering. · source_derived_draft · unverified_draft
## resveratrol-calcium-chelation Removing available signaling calcium weakened the response. Intracellular calcium chelation with BAPTA-AM reduced AMPK and ACC phosphorylation induced by 50 micromolar resveratrol in mouse C2C12 myotubes. Model: Pharmacological intracellular calcium buffering. Limitations: This is not a dietary calcium-deficiency threshold. Evidence access: Primary full text Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
Complete structured claim and evidence
STO609 reduced the mouse C2C12 AMPK response to 50 micromolar resveratrol but not to 300 micromolar.
Mouse CaMKK beta / Camkk2 → Mouse AMPK complexes source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Pharmacological CaMKK inhibition; two resveratrol concentrations.
limitations
Inhibitor specificity limits isoform-level certainty.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Higher exposure can bypass the calcium-dependent kinase route.
primary_references
Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pharmacological CaMKK inhibition; two resveratrol concentrations. · source_derived_draft · unverified_draft
## resveratrol-camkk-block Higher exposure can bypass the calcium-dependent kinase route. STO609 reduced the mouse C2C12 AMPK response to 50 micromolar resveratrol but not to 300 micromolar. Model: Pharmacological CaMKK inhibition; two resveratrol concentrations. Limitations: Inhibitor specificity limits isoform-level certainty. Evidence access: Primary full text Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
Complete structured claim and evidence
The PLC inhibitor U73122 reduced the intracellular calcium rise and AMPK/ACC phosphorylation after resveratrol in mouse C2C12 cells.
U73122, pharmacological PLC inhibitor → Resveratrol-induced calcium increase in mouse C2C12 cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
50 micromolar resveratrol cell experiments.
limitations
Supports PLC involvement; this inhibitor alone does not isolate PLC-epsilon.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A phospholipase-linked step lies upstream of calcium signaling.
primary_references
Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 50 micromolar resveratrol cell experiments. · source_derived_draft · unverified_draft
## resveratrol-plc-calcium A phospholipase-linked step lies upstream of calcium signaling. The PLC inhibitor U73122 reduced the intracellular calcium rise and AMPK/ACC phosphorylation after resveratrol in mouse C2C12 cells. Model: 50 micromolar resveratrol cell experiments. Limitations: Supports PLC involvement; this inhibitor alone does not isolate PLC-epsilon. Evidence access: Primary full text Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
Complete structured claim and evidence
Ryanodine prevented resveratrol-induced AMPK/ACC phosphorylation in mouse C2C12 myotubes, supporting a ryanodine-receptor calcium-release route.
Mouse ryanodine receptor 2 / Ryr2 → Mouse AMPK complexes source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Pharmacological channel inhibition.
limitations
Does not establish direct resveratrol binding to Ryr2.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Stored calcium release connects to the energy-sensing kinase.
primary_references
Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
trigger_kind
machinery_impairment Imported condition classification; unverified.
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 278–284
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pharmacological channel inhibition. · source_derived_draft · unverified_draft
## resveratrol-ryr-block Stored calcium release connects to the energy-sensing kinase. Ryanodine prevented resveratrol-induced AMPK/ACC phosphorylation in mouse C2C12 myotubes, supporting a ryanodine-receptor calcium-release route. Model: Pharmacological channel inhibition. Limitations: Does not establish direct resveratrol binding to Ryr2. Evidence access: Primary full text Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017
Complete structured claim and evidence
Resveratrol occupied the tyrosine active site in human TyrRS co-crystals and inhibited amino-acid activation with reported Ki 22 micromolar.
Resveratrol → Human cytosolic tyrosyl-tRNA synthetase / YARS1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified human enzyme and structure.
limitations
The bound ligand adopts a cis conformation; the authors propose conformational accommodation from predominantly trans solution. This is not proof of physiological bulk photoisomerization.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A protein that normally charges tyrosine tRNA also senses this compound.
primary_references
A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 286–292
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme and structure. · source_derived_draft · unverified_draft
## resveratrol-tyrrs-binding A protein that normally charges tyrosine tRNA also senses this compound. Resveratrol occupied the tyrosine active site in human TyrRS co-crystals and inhibited amino-acid activation with reported Ki 22 micromolar. Model: Purified human enzyme and structure. Limitations: The bound ligand adopts a cis conformation; the authors propose conformational accommodation from predominantly trans solution. This is not proof of physiological bulk photoisomerization. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Complete structured claim and evidence
Resveratrol promoted endogenous TyrRS nuclear translocation in human HeLa cells, coincident with PARP1 auto-PARylation.
Resveratrol → Human cytosolic tyrosyl-tRNA synthetase / YARS1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
HeLa time-course and purified interaction experiments.
limitations
Compartment change is not general inhibition of protein synthesis in humans.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
An amino-acid enzyme moves into a stress-signaling role.
primary_references
A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 294–300
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HeLa time-course and purified interaction experiments. · source_derived_draft · unverified_draft
## resveratrol-tyrrs-nucleus An amino-acid enzyme moves into a stress-signaling role. Resveratrol promoted endogenous TyrRS nuclear translocation in human HeLa cells, coincident with PARP1 auto-PARylation. Model: HeLa time-course and purified interaction experiments. Limitations: Compartment change is not general inhibition of protein synthesis in humans. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Complete structured claim and evidence
In the resveratrol study, human TyrRS stimulated NAD-dependent PARP1 auto-poly-ADP-ribosylation in biochemical experiments.
Human cytosolic tyrosyl-tRNA synthetase / YARS1 → Human PARP1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified-protein interaction/activation assays.
limitations
Greater PARylation need not imply greater net NAD stores.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
This signaling step consumes a niacin-derived cofactor.
primary_references
A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 302–308
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified-protein interaction/activation assays. · source_derived_draft · unverified_draft
## resveratrol-tyrrs-parp This signaling step consumes a niacin-derived cofactor. In the resveratrol study, human TyrRS stimulated NAD-dependent PARP1 auto-poly-ADP-ribosylation in biochemical experiments. Model: Purified-protein interaction/activation assays. Limitations: Greater PARylation need not imply greater net NAD stores. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Complete structured claim and evidence
In human HeLa cells, resveratrol initially reduced NAD with increased nicotinamide/ADP-ribose at 15 minutes; low concentrations raised NAD by one hour.
Resveratrol → NAD content in human HeLa cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Low-dose time course; 5 micromolar used in dependency experiments.
limitations
Whole-cell NAD is not a measurement of every subcellular pool.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Initial consumption and later replenishment are separate phases.
primary_references
A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 310–316
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Low-dose time course; 5 micromolar used in dependency experiments. · source_derived_draft · unverified_draft
## resveratrol-nad-timecourse Initial consumption and later replenishment are separate phases. In human HeLa cells, resveratrol initially reduced NAD with increased nicotinamide/ADP-ribose at 15 minutes; low concentrations raised NAD by one hour. Model: Low-dose time course; 5 micromolar used in dependency experiments. Limitations: Whole-cell NAD is not a measurement of every subcellular pool. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Complete structured claim and evidence
Silencing TyrRS abolished the one-hour NAD increase induced by low-dose resveratrol in human HeLa cells.
Human cytosolic tyrosyl-tRNA synthetase / YARS1 → NAD content in human HeLa cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
siRNA experiments; 5 micromolar resveratrol.
limitations
Cell-model dependency, not a dietary resveratrol-deficiency state.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Removing a signaling component prevented the rebound.
primary_references
A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
trigger_kind
machinery_impairment Imported condition classification; unverified.
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 318–324
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · siRNA experiments; 5 micromolar resveratrol. · source_derived_draft · unverified_draft
## resveratrol-tyrrs-loss Removing a signaling component prevented the rebound. Silencing TyrRS abolished the one-hour NAD increase induced by low-dose resveratrol in human HeLa cells. Model: siRNA experiments; 5 micromolar resveratrol. Limitations: Cell-model dependency, not a dietary resveratrol-deficiency state. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Complete structured claim and evidence
Silencing PARP1 abolished the one-hour NAD increase induced by low-dose resveratrol in human HeLa cells.
Human PARP1 → NAD content in human HeLa cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
siRNA experiments; 5 micromolar resveratrol.
limitations
Cell-model dependency, not a dietary resveratrol-deficiency state.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Removing a signaling component prevented the rebound.
primary_references
A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
trigger_kind
machinery_impairment Imported condition classification; unverified.
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 326–332
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · siRNA experiments; 5 micromolar resveratrol. · source_derived_draft · unverified_draft
## resveratrol-parp-loss Removing a signaling component prevented the rebound. Silencing PARP1 abolished the one-hour NAD increase induced by low-dose resveratrol in human HeLa cells. Model: siRNA experiments; 5 micromolar resveratrol. Limitations: Cell-model dependency, not a dietary resveratrol-deficiency state. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Complete structured claim and evidence
NAD depletion with NAMPT inhibitor STF-118804 abolished resveratrol-mediated induction of BRCA1, FOXO3A, NAMPT, SESN2 and SIRT6 in human HeLa cells.
Human nicotinamide phosphoribosyltransferase / NAMPT → Resveratrol-induced stress-protein response in human HeLa cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Pharmacological NAMPT inhibition.
limitations
This does not prove supplementation with niacin, NR or NMN improves the response.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
The response needs functioning NAD salvage machinery.
primary_references
A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
trigger_kind
machinery_impairment Imported condition classification; unverified.
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 334–340
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pharmacological NAMPT inhibition. · source_derived_draft · unverified_draft
## resveratrol-nampt-block The response needs functioning NAD salvage machinery. NAD depletion with NAMPT inhibitor STF-118804 abolished resveratrol-mediated induction of BRCA1, FOXO3A, NAMPT, SESN2 and SIRT6 in human HeLa cells. Model: Pharmacological NAMPT inhibition. Limitations: This does not prove supplementation with niacin, NR or NMN improves the response. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Complete structured claim and evidence
Resveratrol inhibited recombinant human HLCS-dependent biotinylation in vitro, with reported IC50 approximately 3.70 micromolar.
Resveratrol → Human holocarboxylase synthetase / HLCS source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Gel-based biotin-acceptor assay and dose response.
limitations
Human biotin depletion or failure of biotin repletion was not demonstrated.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A direct laboratory connection to biotin activation is searchable.
primary_references
Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26303405/ · DOI 10.1016/j.jnutbio.2015.07.004
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Gel-based biotin-acceptor assay and dose response. · source_derived_draft · unverified_draft
## resveratrol-hlcs-inhibition A direct laboratory connection to biotin activation is searchable. Resveratrol inhibited recombinant human HLCS-dependent biotinylation in vitro, with reported IC50 approximately 3.70 micromolar. Model: Gel-based biotin-acceptor assay and dose response. Limitations: Human biotin depletion or failure of biotin repletion was not demonstrated. Evidence access: Primary full text Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26303405/ · DOI 10.1016/j.jnutbio.2015.07.004
Complete structured claim and evidence
In the human HLCS assay, inhibitory potency ranked piceatannol above resveratrol above piceid.
Piceatannol → Piceid / polydatin source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified-compound enzyme comparison.
limitations
Does not mean all are circulating resveratrol metabolites under a given regimen.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Related compounds cannot be assigned identical potency.
primary_references
Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26303405/ · DOI 10.1016/j.jnutbio.2015.07.004
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 350–356
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified-compound enzyme comparison. · source_derived_draft · unverified_draft
## resveratrol-hlcs-forms Related compounds cannot be assigned identical potency. In the human HLCS assay, inhibitory potency ranked piceatannol above resveratrol above piceid. Model: Purified-compound enzyme comparison. Limitations: Does not mean all are circulating resveratrol metabolites under a given regimen. Evidence access: Primary full text Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26303405/ · DOI 10.1016/j.jnutbio.2015.07.004
Complete structured claim and evidence
Grape-leaf feeding increased HLCS protein and biotinylated carboxylases in Drosophila brummer mutants despite the extract inhibiting human HLCS in vitro.
Grape-leaf-extract intervention → Biotinylated carboxylases in Drosophila brummer mutants source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Fly feeding; grape extract, with separate piceid body-fat experiments.
limitations
Not purified resveratrol exposure; reduced fly fat was not explained by lost carboxylase biotinylation.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Compensatory expression can reverse an isolated-enzyme prediction.
primary_references
Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26303405/ · DOI 10.1016/j.jnutbio.2015.07.004
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 358–364
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Fly feeding; grape extract, with separate piceid body-fat experiments. · source_derived_draft · unverified_draft
## resveratrol-fly-compensation Compensatory expression can reverse an isolated-enzyme prediction. Grape-leaf feeding increased HLCS protein and biotinylated carboxylases in Drosophila brummer mutants despite the extract inhibiting human HLCS in vitro. Model: Fly feeding; grape extract, with separate piceid body-fat experiments. Limitations: Not purified resveratrol exposure; reduced fly fat was not explained by lost carboxylase biotinylation. Evidence access: Primary full text Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26303405/ · DOI 10.1016/j.jnutbio.2015.07.004
Complete structured claim and evidence
Resveratrol/copper treatment produced plasmid sequence mutations and reduced transformation efficiency in a cell-free DNA/bacterial readout experiment.
Resveratrol → Plasmid DNA injury during resveratrol/copper exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Plasmid treatment followed by E. coli transformation/sequencing.
limitations
Not demonstrated human mutagenicity from dietary resveratrol.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Copper can change an antioxidant into a pro-oxidant in an assay.
primary_references
Prooxidant activity of resveratrol in the presence of copper ions: mutagenicity in plasmid DNA. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15913925/ · DOI 10.1016/j.toxlet.2005.04.001
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Plasmid treatment followed by E. coli transformation/sequencing. · source_derived_draft · unverified_draft
## resveratrol-copper-dna Copper can change an antioxidant into a pro-oxidant in an assay. Resveratrol/copper treatment produced plasmid sequence mutations and reduced transformation efficiency in a cell-free DNA/bacterial readout experiment. Model: Plasmid treatment followed by E. coli transformation/sequencing. Limitations: Not demonstrated human mutagenicity from dietary resveratrol. Evidence access: Primary abstract Prooxidant activity of resveratrol in the presence of copper ions: mutagenicity in plasmid DNA. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15913925/ · DOI 10.1016/j.toxlet.2005.04.001
Complete structured claim and evidence
With ascorbate present, resveratrol protected DNA in copper-based chemical experiments without lowering hydroxyl-radical formation rate, consistent with radical scavenging.
Resveratrol → DNA integrity in copper/ascorbate chemical assays source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cell-free DNA-bound copper system.
limitations
Authors inferred physiological relevance; this experiment does not establish systemic safety or clinical synergy.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Vitamin C changes the relevant chemical context.
primary_references
Effects of trans-resveratrol on copper-dependent hydroxyl-radical formation and DNA damage: evidence for hydroxyl-radical scavenging and a novel, glutathione-sparing mechanism of action. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11032413/ · DOI 10.1006/abbi.2000.1973
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 374–380
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free DNA-bound copper system. · source_derived_draft · unverified_draft
## resveratrol-ascorbate-context Vitamin C changes the relevant chemical context. With ascorbate present, resveratrol protected DNA in copper-based chemical experiments without lowering hydroxyl-radical formation rate, consistent with radical scavenging. Model: Cell-free DNA-bound copper system. Limitations: Authors inferred physiological relevance; this experiment does not establish systemic safety or clinical synergy. Evidence access: Primary abstract Effects of trans-resveratrol on copper-dependent hydroxyl-radical formation and DNA damage: evidence for hydroxyl-radical scavenging and a novel, glutathione-sparing mechanism of action. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11032413/ · DOI 10.1006/abbi.2000.1973
Complete structured claim and evidence
In the glutathione-containing copper system, resveratrol reduced radical formation and glutathione-disulfide formation.
Resveratrol → Hydroxyl-radical generation in copper/glutathione assays source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Chemical assay with glutathione versus ascorbate conditions.
limitations
Not a measurement of GSH synthesis, recycling or depletion in humans.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Glutathione changes the redox reaction rather than merely adding another antioxidant label.
primary_references
Effects of trans-resveratrol on copper-dependent hydroxyl-radical formation and DNA damage: evidence for hydroxyl-radical scavenging and a novel, glutathione-sparing mechanism of action. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11032413/ · DOI 10.1006/abbi.2000.1973
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Chemical assay with glutathione versus ascorbate conditions. · source_derived_draft · unverified_draft
## resveratrol-gsh-context Glutathione changes the redox reaction rather than merely adding another antioxidant label. In the glutathione-containing copper system, resveratrol reduced radical formation and glutathione-disulfide formation. Model: Chemical assay with glutathione versus ascorbate conditions. Limitations: Not a measurement of GSH synthesis, recycling or depletion in humans. Evidence access: Primary abstract Effects of trans-resveratrol on copper-dependent hydroxyl-radical formation and DNA damage: evidence for hydroxyl-radical scavenging and a novel, glutathione-sparing mechanism of action. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11032413/ · DOI 10.1006/abbi.2000.1973
Complete structured claim and evidence
Copper-specific chelators, unlike tested iron/zinc chelators, inhibited resveratrol-associated DNA breakage in isolated human lymphocyte and nuclear experiments.
Copper-specific chelation → Resveratrol-associated DNA breakage in isolated human lymphocytes source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Isolated cells, permeabilized cells and nuclei.
limitations
Cancer-selective killing was a proposed interpretation, not demonstrated clinical benefit.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A metal-specific rescue helps identify the assay mechanism.
primary_references
Resveratrol mobilizes endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for chemoprevention of cancer. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20119749/ · DOI 10.1007/s11095-010-0055-4
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated cells, permeabilized cells and nuclei. · source_derived_draft · unverified_draft
## resveratrol-copper-chelator-rescue A metal-specific rescue helps identify the assay mechanism. Copper-specific chelators, unlike tested iron/zinc chelators, inhibited resveratrol-associated DNA breakage in isolated human lymphocyte and nuclear experiments. Model: Isolated cells, permeabilized cells and nuclei. Limitations: Cancer-selective killing was a proposed interpretation, not demonstrated clinical benefit. Evidence access: Primary abstract Resveratrol mobilizes endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for chemoprevention of cancer. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20119749/ · DOI 10.1007/s11095-010-0055-4
Complete structured claim and evidence
Resveratrol bound ERalpha and ERbeta with comparable affinity, approximately 7,000-fold weaker than estradiol in the reported assays.
trans-Resveratrol → Human estrogen receptor alpha / ESR1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Receptor binding and CHO-K1 reporter experiments.
limitations
No demonstrated hormone normalization in humans.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
It can interact with hormone receptors, but weak affinity matters.
primary_references
Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11014220/ · DOI 10.1210/endo.141.10.7721
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Receptor binding and CHO-K1 reporter experiments. · source_derived_draft · unverified_draft
## resveratrol-er-binding It can interact with hormone receptors, but weak affinity matters. Resveratrol bound ERalpha and ERbeta with comparable affinity, approximately 7,000-fold weaker than estradiol in the reported assays. Model: Receptor binding and CHO-K1 reporter experiments. Limitations: No demonstrated hormone normalization in humans. Evidence access: Primary abstract Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11014220/ · DOI 10.1210/endo.141.10.7721
Complete structured claim and evidence
Resveratrol acted as an estrogen agonist in ERalpha/ERbeta reporter systems; selected ERE sequences also showed estradiol antagonism with ERalpha but not ERbeta.
trans-Resveratrol → Human estrogen receptor beta / ESR2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Transfected CHO-K1 reporter cells.
limitations
Normal experimental context dependence, not an unresolved contradiction.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Direction depends on receptor and gene-control sequence.
primary_references
Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11014220/ · DOI 10.1210/endo.141.10.7721
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Transfected CHO-K1 reporter cells. · source_derived_draft · unverified_draft
## resveratrol-er-sequence Direction depends on receptor and gene-control sequence. Resveratrol acted as an estrogen agonist in ERalpha/ERbeta reporter systems; selected ERE sequences also showed estradiol antagonism with ERalpha but not ERbeta. Model: Transfected CHO-K1 reporter cells. Limitations: Normal experimental context dependence, not an unresolved contradiction. Evidence access: Primary abstract Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11014220/ · DOI 10.1210/endo.141.10.7721
Complete structured claim and evidence
After 1 g/day resveratrol for four weeks, the healthy-volunteer study found increased CYP1A2 phenotypic activity using caffeine as the probe.
Resveratrol → Human cytochrome P450 1A2 source_derived_draftungraded
Experimental context and source evidence
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
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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-cyp1a2 A human drug-metabolism interaction was measured with a specific probe. After 1 g/day resveratrol for four weeks, the healthy-volunteer study found increased CYP1A2 phenotypic activity using caffeine 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
Complete structured claim and evidence
After 1 g/day resveratrol for four weeks, the healthy-volunteer study found decreased CYP2D6 phenotypic activity using dextromethorphan as the probe.
Resveratrol → Human cytochrome P450 2D6 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
After 1 g/day resveratrol for four weeks, the healthy-volunteer study found decreased CYP2C9 phenotypic activity using losartan as the probe.
Resveratrol → Human cytochrome P450 2C9 source_derived_draftungraded
Experimental context and source evidence
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 430–436
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-cyp2c9 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 CYP2C9 phenotypic activity using losartan 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
Complete structured claim and evidence
After 1 g/day resveratrol for four weeks, the healthy-volunteer study found decreased CYP3A4 phenotypic activity using buspirone as the probe.
Resveratrol → Human cytochrome P450 3A4 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Overall lymphocyte GST and bilirubin-based UGT1A1 indices changed minimally after resveratrol, with larger changes reported in low-baseline subgroups.
Resveratrol → Human phase-II enzyme indices after resveratrol source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same four-week volunteer study.
limitations
Bilirubin was a surrogate; this was not a direct hepatic UGT flux measurement.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A subgroup signal is not a universal detoxification effect.
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 446–452
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same four-week volunteer study. · source_derived_draft · unverified_draft
## resveratrol-human-phase2 A subgroup signal is not a universal detoxification effect. Overall lymphocyte GST and bilirubin-based UGT1A1 indices changed minimally after resveratrol, with larger changes reported in low-baseline subgroups. Model: Same four-week volunteer study. Limitations: Bilirubin was a surrogate; this was not a direct hepatic UGT flux measurement. Evidence access: Primary abstract 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
Complete structured claim and evidence
In 11 obese men, 150 mg/day resveratrol for 30 days increased muscle AMPK activation and SIRT1/PGC-1alpha protein, improved fatty-acid-supported mitochondrial respiration and reduced liver fat and selected metabolic markers.
Resveratrol → Metabolic response to resveratrol in obese men source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Randomized double-blind crossover; resVida preparation.
limitations
HOMA is not a clamp; no increase in mitochondrial content and no long-term disease outcome were demonstrated.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A small controlled human study found several metabolic changes.
primary_references
Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22055504/ · DOI 10.1016/j.cmet.2011.10.002
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 454–460
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized double-blind crossover; resVida preparation. · source_derived_draft · unverified_draft
## resveratrol-human-metabolic-positive A small controlled human study found several metabolic changes. In 11 obese men, 150 mg/day resveratrol for 30 days increased muscle AMPK activation and SIRT1/PGC-1alpha protein, improved fatty-acid-supported mitochondrial respiration and reduced liver fat and selected metabolic markers. Model: Randomized double-blind crossover; resVida preparation. Limitations: HOMA is not a clamp; no increase in mitochondrial content and no long-term disease outcome were demonstrated. Evidence access: Primary abstract Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22055504/ · DOI 10.1016/j.cmet.2011.10.002
Complete structured claim and evidence
In a randomized 24-man obesity trial, 1,500 mg/day resveratrol for four weeks did not improve clamp-measured insulin sensitivity, glucose turnover, ectopic fat or the measured metabolic/inflammatory outcomes.
Resveratrol → Human clamp-measured insulin sensitivity after resveratrol source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Parallel placebo-controlled trial in otherwise healthy obese men.
limitations
Different dose, design and endpoints from the 11-person crossover; difference alone is not a scientific contradiction.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A larger dose did not reproduce a universal metabolic benefit.
primary_references
High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23193181/ · DOI 10.2337/db12-0975
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Parallel placebo-controlled trial in otherwise healthy obese men. · source_derived_draft · unverified_draft
## resveratrol-human-metabolic-null A larger dose did not reproduce a universal metabolic benefit. In a randomized 24-man obesity trial, 1,500 mg/day resveratrol for four weeks did not improve clamp-measured insulin sensitivity, glucose turnover, ectopic fat or the measured metabolic/inflammatory outcomes. Model: Parallel placebo-controlled trial in otherwise healthy obese men. Limitations: Different dose, design and endpoints from the 11-person crossover; difference alone is not a scientific contradiction. Evidence access: Primary full text High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23193181/ · DOI 10.2337/db12-0975
Complete structured claim and evidence
In nonobese postmenopausal women with normal glucose tolerance, 75 mg/day resveratrol for 12 weeks did not improve liver, muscle or adipose insulin sensitivity or measured AMPK/SIRT1/NAMPT/PPARGC1A targets.
Resveratrol → Metabolic outcomes in nonobese postmenopausal women source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Randomized double-blind placebo-controlled trial.
limitations
Null result is population- and regimen-specific.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Effects in metabolically abnormal models do not automatically transfer to healthy people.
primary_references
Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23102619/ · DOI 10.1016/j.cmet.2012.09.015
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial. · source_derived_draft · unverified_draft
## resveratrol-human-women-null Effects in metabolically abnormal models do not automatically transfer to healthy people. In nonobese postmenopausal women with normal glucose tolerance, 75 mg/day resveratrol for 12 weeks did not improve liver, muscle or adipose insulin sensitivity or measured AMPK/SIRT1/NAMPT/PPARGC1A targets. Model: Randomized double-blind placebo-controlled trial. Limitations: Null result is population- and regimen-specific. Evidence access: Primary abstract Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23102619/ · DOI 10.1016/j.cmet.2012.09.015
Complete structured claim and evidence
In 27 inactive older men training for eight weeks, 250 mg/day trans-resveratrol attenuated gains in maximal oxygen uptake and several cardiovascular/lipid outcomes relative to placebo.
Resveratrol → Cardiovascular adaptation to training in older men source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Randomized exercise-plus-supplement trial, 14 resveratrol and 13 placebo.
limitations
Not evidence that all exercise benefits disappear or every antioxidant has the same effect.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Adding a supplement did not necessarily improve the exercise response.
primary_references
Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23878368/ · DOI 10.1113/jphysiol.2013.258061
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized exercise-plus-supplement trial, 14 resveratrol and 13 placebo. · source_derived_draft · unverified_draft
## resveratrol-exercise-adaptation Adding a supplement did not necessarily improve the exercise response. In 27 inactive older men training for eight weeks, 250 mg/day trans-resveratrol attenuated gains in maximal oxygen uptake and several cardiovascular/lipid outcomes relative to placebo. Model: Randomized exercise-plus-supplement trial, 14 resveratrol and 13 placebo. Limitations: Not evidence that all exercise benefits disappear or every antioxidant has the same effect. Evidence access: Primary abstract Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23878368/ · DOI 10.1113/jphysiol.2013.258061
Complete structured claim and evidence
The related older-men study found no additive or adverse resveratrol effect on several exercise-induced mitochondrial/endurance measures, but blunting of reduced protein carbonylation and TNF-alpha mRNA.
Resveratrol → Skeletal-muscle response to exercise/resveratrol in older men source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Eight weeks, 250 mg/day; overlapping training investigation with additional nontraining arms.
limitations
Do not count related reports as independent replications or confuse muscle endpoints with the cardiovascular report.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Different outcomes within an exercise program can move differently.
primary_references
Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24514907/ · DOI 10.1113/jphysiol.2013.270256
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 486–492
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Eight weeks, 250 mg/day; overlapping training investigation with additional nontraining arms. · source_derived_draft · unverified_draft
## resveratrol-exercise-muscle-specificity Different outcomes within an exercise program can move differently. The related older-men study found no additive or adverse resveratrol effect on several exercise-induced mitochondrial/endurance measures, but blunting of reduced protein carbonylation and TNF-alpha mRNA. Model: Eight weeks, 250 mg/day; overlapping training investigation with additional nontraining arms. Limitations: Do not count related reports as independent replications or confuse muscle endpoints with the cardiovascular report. Evidence access: Primary abstract Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24514907/ · DOI 10.1113/jphysiol.2013.270256
Complete structured claim and evidence
Resveratrol improved survival and several metabolic measures in middle-aged mice on a high-calorie diet compared with high-calorie controls.
Resveratrol → Survival of high-calorie-fed mice source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
High-calorie mouse model.
limitations
Not proof of lifespan extension in healthy humans or all mouse diets.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Rescuing diet-associated harm is a specific survival result.
primary_references
Resveratrol improves health and survival of mice on a high-calorie diet. · 2006 · https://pubmed.ncbi.nlm.nih.gov/17086191/ · DOI 10.1038/nature05354
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · High-calorie mouse model. · source_derived_draft · unverified_draft
## resveratrol-high-calorie-mouse-survival Rescuing diet-associated harm is a specific survival result. Resveratrol improved survival and several metabolic measures in middle-aged mice on a high-calorie diet compared with high-calorie controls. Model: High-calorie mouse model. Limitations: Not proof of lifespan extension in healthy humans or all mouse diets. Evidence access: Primary abstract Resveratrol improves health and survival of mice on a high-calorie diet. · 2006 · https://pubmed.ncbi.nlm.nih.gov/17086191/ · DOI 10.1038/nature05354
Complete structured claim and evidence
Resveratrol started at 12 months did not extend lifespan of ad-libitum standard-diet mice despite improvements in several age-associated outcomes.
Resveratrol → Lifespan of standard-diet mice source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Related mouse-aging research program.
limitations
Diet and start age differ from other lifespan designs.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Health-related changes and longevity are different endpoints.
primary_references
Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18599363/ · DOI 10.1016/j.cmet.2008.06.011
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 502–508
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Related mouse-aging research program. · source_derived_draft · unverified_draft
## resveratrol-standard-diet-mouse-survival Health-related changes and longevity are different endpoints. Resveratrol started at 12 months did not extend lifespan of ad-libitum standard-diet mice despite improvements in several age-associated outcomes. Model: Related mouse-aging research program. Limitations: Diet and start age differ from other lifespan designs. Evidence access: Primary abstract Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18599363/ · DOI 10.1016/j.cmet.2008.06.011
Complete structured claim and evidence
In the 33-male RESTRIKAL cohort, long-term 200 mg/kg/day resveratrol did not significantly reduce all-cause or age-related mortality despite a higher observed median lifespan.
Resveratrol → Mortality in resveratrol-fed male mouse lemurs source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
18 resveratrol and 15 controls; lifelong follow-up.
limitations
Small male-only nonhuman-primate cohort; earlier reports from this program are not independent samples.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A higher sample median is not automatically a demonstrated survival benefit.
primary_references
Resveratrol does not mimic the positive effects of calorie restriction on lifespan in Microcebus murinus. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40021720/ · DOI 10.1038/s42003-024-07387-9
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 510–516
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 18 resveratrol and 15 controls; lifelong follow-up. · source_derived_draft · unverified_draft
## resveratrol-lemur-mortality A higher sample median is not automatically a demonstrated survival benefit. In the 33-male RESTRIKAL cohort, long-term 200 mg/kg/day resveratrol did not significantly reduce all-cause or age-related mortality despite a higher observed median lifespan. Model: 18 resveratrol and 15 controls; lifelong follow-up. Limitations: Small male-only nonhuman-primate cohort; earlier reports from this program are not independent samples. Evidence access: Primary full text Resveratrol does not mimic the positive effects of calorie restriction on lifespan in Microcebus murinus. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40021720/ · DOI 10.1038/s42003-024-07387-9
Complete structured claim and evidence
Long-term resveratrol was associated with faster late-life grey-matter atrophy in the male mouse-lemur study, while middle-age motor/cognitive performance had improved.
Resveratrol → Grey-matter atrophy in resveratrol-fed male mouse lemurs source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Longitudinal MRI subset; behavioral and imaging windows differed.
limitations
Does not establish human neurotoxicity or a causal link between the different measurement windows.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Potential benefit and adverse findings remain visible together.
primary_references
Resveratrol does not mimic the positive effects of calorie restriction on lifespan in Microcebus murinus. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40021720/ · DOI 10.1038/s42003-024-07387-9
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 518–524
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Longitudinal MRI subset; behavioral and imaging windows differed. · source_derived_draft · unverified_draft
## resveratrol-lemur-brain Potential benefit and adverse findings remain visible together. Long-term resveratrol was associated with faster late-life grey-matter atrophy in the male mouse-lemur study, while middle-age motor/cognitive performance had improved. Model: Longitudinal MRI subset; behavioral and imaging windows differed. Limitations: Does not establish human neurotoxicity or a causal link between the different measurement windows. Evidence access: Primary full text Resveratrol does not mimic the positive effects of calorie restriction on lifespan in Microcebus murinus. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40021720/ · DOI 10.1038/s42003-024-07387-9
Complete structured claim and evidence
Resveratrol inhibited cyclooxygenase and hydroperoxidase functions in the original chemoprevention assay program.
Resveratrol → Cyclooxygenase/hydroperoxidase activities in Jang 1997 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Biochemical assays accompanying cell, mammary-organ and mouse-skin experiments.
limitations
Abstract does not resolve every enzyme isoform; not a clinical anticancer claim.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Inflammatory lipid-enzyme chemistry was an early experimental branch.
primary_references
Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. · 1997 · https://pubmed.ncbi.nlm.nih.gov/8985016/ · DOI 10.1126/science.275.5297.218
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 526–532
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biochemical assays accompanying cell, mammary-organ and mouse-skin experiments. · source_derived_draft · unverified_draft
## resveratrol-cox-functions Inflammatory lipid-enzyme chemistry was an early experimental branch. Resveratrol inhibited cyclooxygenase and hydroperoxidase functions in the original chemoprevention assay program. Model: Biochemical assays accompanying cell, mammary-organ and mouse-skin experiments. Limitations: Abstract does not resolve every enzyme isoform; not a clinical anticancer claim. Evidence access: Primary abstract Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. · 1997 · https://pubmed.ncbi.nlm.nih.gov/8985016/ · DOI 10.1126/science.275.5297.218
Complete structured claim and evidence
Resveratrol inhibited tumorigenesis in the reported mouse-skin model and preneoplastic lesions in carcinogen-treated mouse mammary glands in culture.
Resveratrol → Mouse skin tumorigenesis during resveratrol treatment source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse skin and organ-culture assays.
limitations
No human efficacy estimate follows.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Preclinical disease models are preserved without becoming human treatment claims.
primary_references
Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. · 1997 · https://pubmed.ncbi.nlm.nih.gov/8985016/ · DOI 10.1126/science.275.5297.218
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 534–540
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse skin and organ-culture assays. · source_derived_draft · unverified_draft
## resveratrol-skin-tumor-model Preclinical disease models are preserved without becoming human treatment claims. Resveratrol inhibited tumorigenesis in the reported mouse-skin model and preneoplastic lesions in carcinogen-treated mouse mammary glands in culture. Model: Mouse skin and organ-culture assays. Limitations: No human efficacy estimate follows. Evidence access: Primary abstract Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. · 1997 · https://pubmed.ncbi.nlm.nih.gov/8985016/ · DOI 10.1126/science.275.5297.218
Complete structured claim and evidence
HLCS activates biotin with ATP to form enzyme-bound biotinyl-5-prime-AMP before transferring biotin to a carboxylase acceptor.
Human holocarboxylase synthetase / HLCS → Biotinyl-5-prime-AMP source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
Purified full-length and residue-58 human HLCS isoforms expressed in E. coli
exposure
Biotin/ATP activation and single-turnover biotin transfer
limitations
Minimal-substrate kinetics do not prove a universal tissue allocation hierarchy; expression host is not the protein species.
nutrient_topic
Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
organism
Homo sapiens
plain_language
Biotin must first be activated before it can be attached to an enzyme.
primary_references
[b7-p19740736] Distinct amino termini of two human HCS isoforms influence biotin acceptor substrate recognition. (2009). https://pubmed.ncbi.nlm.nih.gov/19740736/ DOI: 10.1074/jbc.m109.046201
tissue_or_cell_type
Purified proteins and minimal biotin-accepting substrate
Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 351–362
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified full-length and residue-58 human HLCS isoforms expressed in E. coli · source_derived_draft · unverified_draft
### b7-hlcs-adenylation HLCS activates biotin with ATP to form enzyme-bound biotinyl-5-prime-AMP before transferring biotin to a carboxylase acceptor. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Biotin must first be activated before it can be attached to an enzyme. organism: Homo sapiens tissue_or_cell_type: Purified proteins and minimal biotin-accepting substrate experimental_model: Purified full-length and residue-58 human HLCS isoforms expressed in E. coli limitations: Minimal-substrate kinetics do not prove a universal tissue allocation hierarchy; expression host is not the protein species. exposure: Biotin/ATP activation and single-turnover biotin transfer evidence_span: {"source_cache": "artifacts/biotin-research/19740736.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d785655901465bc9798378986d954b87111e3bd73d6877d9d60ae3d95cac0a37", "start_char": 2587, "end_char": 3080, "text_sha256": "fa0ec838311a45e8ccebf38a73e340a46417eae6bc300064c1165a4a0b711889"} [b7-p19740736] Distinct amino termini of two human HCS isoforms influence biotin acceptor substrate recognition. (2009). https://pubmed.ncbi.nlm.nih.gov/19740736/ DOI: 10.1074/jbc.m109.046201
Complete structured claim and evidence
HLCS transfers the activated biotin moiety to the epsilon-amino group of a specific lysine in a carboxylase biotin-acceptor domain.
Human holocarboxylase synthetase / HLCS → Protein-bound lysine residue source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/biotin-research/19740736.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d785655901465bc9798378986d954b87111e3bd73d6877d9d60ae3d95cac0a37", "start_char": 2587, "end_char": 3080, "text_sha256": "fa0ec838311a45e8ccebf38a73e340a46417eae6bc300064c1165a4a0b711889"}
experimental_model
Purified full-length and residue-58 human HLCS isoforms expressed in E. coli
exposure
Biotin/ATP activation and single-turnover biotin transfer
limitations
Minimal-substrate kinetics do not prove a universal tissue allocation hierarchy; expression host is not the protein species.
nutrient_topic
Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
organism
Homo sapiens
plain_language
Biotin becomes a tethered part of the enzyme; free lysine and enzyme-bound lysine are different entities.
primary_references
[b7-p19740736] Distinct amino termini of two human HCS isoforms influence biotin acceptor substrate recognition. (2009). https://pubmed.ncbi.nlm.nih.gov/19740736/ DOI: 10.1074/jbc.m109.046201
tissue_or_cell_type
Purified proteins and minimal biotin-accepting substrate
Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 364–375
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified full-length and residue-58 human HLCS isoforms expressed in E. coli · source_derived_draft · unverified_draft
### b7-hlcs-lysine-transfer HLCS transfers the activated biotin moiety to the epsilon-amino group of a specific lysine in a carboxylase biotin-acceptor domain. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Biotin becomes a tethered part of the enzyme; free lysine and enzyme-bound lysine are different entities. organism: Homo sapiens tissue_or_cell_type: Purified proteins and minimal biotin-accepting substrate experimental_model: Purified full-length and residue-58 human HLCS isoforms expressed in E. coli limitations: Minimal-substrate kinetics do not prove a universal tissue allocation hierarchy; expression host is not the protein species. exposure: Biotin/ATP activation and single-turnover biotin transfer evidence_span: {"source_cache": "artifacts/biotin-research/19740736.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d785655901465bc9798378986d954b87111e3bd73d6877d9d60ae3d95cac0a37", "start_char": 2587, "end_char": 3080, "text_sha256": "fa0ec838311a45e8ccebf38a73e340a46417eae6bc300064c1165a4a0b711889"} [b7-p19740736] Distinct amino termini of two human HCS isoforms influence biotin acceptor substrate recognition. (2009). https://pubmed.ncbi.nlm.nih.gov/19740736/ DOI: 10.1074/jbc.m109.046201
Complete structured claim and evidence
Human NAMPT converts nicotinamide and PRPP to nicotinamide mononucleotide and pyrophosphate.
Human nicotinamide phosphoribosyltransferase / NAMPT → NMN source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/nampt2009.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1272, "file_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5", "text_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5"}
experimental_model
Purified human NAMPT reaction monitoring by 1H/31P NMR and substrate/product crystallography
exposure
Biochemical or structural assay; no dietary intervention
limitations
Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Nicotinamide salvage first makes NMN.
primary_references
[b3-pre-nampt2009] Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase. (2010). https://pubmed.ncbi.nlm.nih.gov/19819904/ DOI: 10.1093/jb/mvp152
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 369–380
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human NAMPT reaction monitoring by 1H/31P NMR and substrate/product crystallography · source_derived_draft · unverified_draft
### b3-pre-nampt-reaction Human NAMPT converts nicotinamide and PRPP to nicotinamide mononucleotide and pyrophosphate. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinamide salvage first makes NMN. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human NAMPT reaction monitoring by 1H/31P NMR and substrate/product crystallography limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nampt2009.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1272, "file_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5", "text_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5"} [b3-pre-nampt2009] Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase. (2010). https://pubmed.ncbi.nlm.nih.gov/19819904/ DOI: 10.1093/jb/mvp152
Complete structured claim and evidence
Human SIRT1 removes acetylation from histone H4 Lys16 in an NAD+-dependent reaction.
SIRT1 → Histone H4 acetylated at K16 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human enzyme assays and cultured-cell SIRT1 perturbation.
limitations
This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.
organism
Human
plain_language
A different enzyme removes a lysine modification using NAD+.
primary_references
[sirt1-2004] Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin (2004). https://pubmed.ncbi.nlm.nih.gov/15469825/ DOI: 10.1016/j.molcel.2004.08.031
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 537–545
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme assays and cultured-cell SIRT1 perturbation. · source_derived_draft · unverified_draft
### sirt1-h4k16-deacetylation Human SIRT1 removes acetylation from histone H4 Lys16 in an NAD+-dependent reaction. Plain language: A different enzyme removes a lysine modification using NAD+. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human enzyme assays and cultured-cell SIRT1 perturbation. limitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [sirt1-2004] Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin (2004). https://pubmed.ncbi.nlm.nih.gov/15469825/ DOI: 10.1016/j.molcel.2004.08.031
Complete structured claim and evidence
Melatonin competitively inhibited NQO2 with respect to N-methyldihydronicotinamide, with Ki about 7.2 micromolar.
Melatonin → Human quinone reductase 2 / NQO2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/18254726.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18", "start_char": 0, "end_char": 1724, "text_sha256": "4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18"}
experimental_model
Kinetics, calorimetry and crystal structures
exposure
Melatonin versus N-methyldihydronicotinamide or menadione in enzyme assays
limitations
NQO2 is the historically named MT3 binding site, not a third MT1/MT2-like GPCR. Micromolar inhibition does not establish the dominant effect at physiological blood concentrations.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Purified human NQO2/QR2
plain_language
A redox enzyme is a distinct target from the high-affinity membrane receptors.
primary_references
[melatonin-p18254726] Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. (2008). https://pubmed.ncbi.nlm.nih.gov/18254726/ DOI: 10.1042/bj20071373
tissue_or_cell_type
Cytosolic quinone-reductase active site
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 487–498
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetics, calorimetry and crystal structures · source_derived_draft · unverified_draft
### melatonin-nqo2-cosubstrate-competition Melatonin competitively inhibited NQO2 with respect to N-methyldihydronicotinamide, with Ki about 7.2 micromolar. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A redox enzyme is a distinct target from the high-affinity membrane receptors. organism: Purified human NQO2/QR2 tissue_or_cell_type: Cytosolic quinone-reductase active site experimental_model: Kinetics, calorimetry and crystal structures limitations: NQO2 is the historically named MT3 binding site, not a third MT1/MT2-like GPCR. Micromolar inhibition does not establish the dominant effect at physiological blood concentrations. exposure: Melatonin versus N-methyldihydronicotinamide or menadione in enzyme assays evidence_span: {"source_cache": "artifacts/melatonin-research/18254726.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18", "start_char": 0, "end_char": 1724, "text_sha256": "4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18"} [melatonin-p18254726] Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. (2008). https://pubmed.ncbi.nlm.nih.gov/18254726/ DOI: 10.1042/bj20071373
Complete structured claim and evidence
The THP-1 treatments increased SIRT1 and FOXO3a expression while suppressing high-glucose inflammatory responses.
Fisetin → SIRT1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Fisetin, luteolin and combination conditions in human cells.
limitations
Expression is not proven direct SIRT1 activation or greater NAD availability.
nutrient_topic
Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin
plain_language
This branch connects to NAD-dependent cell regulation.
primary_references
Combination Treatments with Luteolin and Fisetin Enhance Anti-Inflammatory Effects in High Glucose-Treated THP-1 Cells Through Histone Acetyltransferase/Histone Deacetylase Regulation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28650731/ · DOI 10.1089/jmf.2017.3968
Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 456–462
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Fisetin, luteolin and combination conditions in human cells. · source_derived_draft · unverified_draft
## fisetin-sirt1-foxo-response This branch connects to NAD-dependent cell regulation. The THP-1 treatments increased SIRT1 and FOXO3a expression while suppressing high-glucose inflammatory responses. Model: Fisetin, luteolin and combination conditions in human cells. Limitations: Expression is not proven direct SIRT1 activation or greater NAD availability. Evidence access: Primary abstract Combination Treatments with Luteolin and Fisetin Enhance Anti-Inflammatory Effects in High Glucose-Treated THP-1 Cells Through Histone Acetyltransferase/Histone Deacetylase Regulation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28650731/ · DOI 10.1089/jmf.2017.3968
Complete structured claim and evidence

Availability and dependencies

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

Absorbed dose is not circulating free parent

Condition: biomarker_context · Rapid metabolism after oral resveratrol.

Normal role: Exposure interacts with intact transport, conjugation, calcium, NAD and enzyme machinery.

Recorded consequence: A high absorbed fraction coexists with low unconjugated parent.