Resveratrol

evidence_access

Primary full text

experimental_model

Pig jejunum/ileum Ussing chambers; alanine challenge.

limitations

Current is a functional proxy; associated AMPK/PKA changes were not established as the cause. No human malabsorption conclusion follows.

nutrient_topic

L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine

plain_language

A second compound altered the electrical transport response to alanine.

primary_references

Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na⁺/K⁺-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29510506/ · DOI 10.3390/nu10030302

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pig jejunum/ileum Ussing chambers; alanine challenge. · source_derived_draft · unverified_draft

## alanine-intestinal-resveratrol A second compound altered the electrical transport response to alanine. Resveratrol at 300 micromolar for 30 minutes reduced alanine-evoked short-circuit current in isolated porcine intestinal preparations. Model: Pig jejunum/ileum Ussing chambers; alanine challenge. Limitations: Current is a functional proxy; associated AMPK/PKA changes were not established as the cause. No human malabsorption conclusion follows. Evidence access: Primary full text Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na⁺/K⁺-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29510506/ · DOI 10.3390/nu10030302

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

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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

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

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

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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

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

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

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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

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

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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

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

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

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

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

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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

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

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-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

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-cyp2d6 A human drug-metabolism interaction was measured with a specific probe. After 1 g/day resveratrol for four weeks, the healthy-volunteer study found decreased CYP2D6 phenotypic activity using dextromethorphan as the probe. Model: 42 initiated; enzyme activities assessed in 40; before/after pharmacological-dose study. Limitations: Probe indices are not proof of transcriptional induction or a quantified interaction with every substrate; no medication adjustment follows. Evidence access: Primary full text Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20716633/ · DOI 10.1158/1940-6207.CAPR-09-0155

evidence_access

Primary 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-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

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.

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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

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

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

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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 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

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

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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

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

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

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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

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

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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

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

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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

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

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

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

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

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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

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

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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

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

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

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

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

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

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

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

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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

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

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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

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

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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

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

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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

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

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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

evidence_access

Primary abstract

experimental_model

Mouse epidermal cells; study compared 10 micromolar myricetin and 20 micromolar resveratrol.

limitations

Assay-specific interaction, not a universal combination verdict.

nutrient_topic

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

plain_language

Two active compounds did not demonstrate synergy in this test.

primary_references

Myricetin is a novel natural inhibitor of neoplastic cell transformation and MEK1. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17693661/ · DOI 10.1093/carcin/bgm110

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse epidermal cells; study compared 10 micromolar myricetin and 20 micromolar resveratrol. · source_derived_draft · unverified_draft

## myricetin-resveratrol-addition Two active compounds did not demonstrate synergy in this test. Myricetin plus resveratrol inhibited TPA/EGF-induced mouse JB6 transformation additively, not synergistically. Model: Mouse epidermal cells; study compared 10 micromolar myricetin and 20 micromolar resveratrol. Limitations: Assay-specific interaction, not a universal combination verdict. Evidence access: Primary abstract Myricetin is a novel natural inhibitor of neoplastic cell transformation and MEK1. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17693661/ · DOI 10.1093/carcin/bgm110

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

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.

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 254–260

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

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.

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 262–268

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

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

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.

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 238–244

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

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.

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 246–252

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

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

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

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

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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

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

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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

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

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

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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

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

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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

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

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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

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

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

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

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

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.

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 270–276

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

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

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.

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 166–172

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

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

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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

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

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.

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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

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

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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

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

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

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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

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