Resveratrol

Category: polyphenol

Aliases: trans-Resveratrol, 3,5,4'-trihydroxystilbene

Pharmacological Mechanism

Direct nad sirtuin axis SIRT1 activator at high concentrations (disputed — some studies show fluorophore artifact). Also activates ampk signaling, inhibits PDE4, and is a weak ER-α ligand. Extensively glucuronidated + sulfated — plasma aglycone concentration is low even at gram doses. Commonly paired with nmn in 'longevity' stacks.

Half-Life (t½)

PO: 9h

Dosing Guidelines

• PO: Typical 500 mg (Range: 250–1000 mg)

Target Organ Systems

• cardiovascular
• endocrine

Interactions

• NMN (synergistic): SIRT1 activation + NAD⁺ substrate supply. Classic longevity pair.
• Pterostilbene (synergistic): Both stilbenoids; pterostilbene has higher F and similar mechanism.

Pathways It Modulates

• Alzheimer disease (inhibitor) — tau hyperphosphorylation (SIRT1-mediated)
• AMPK energy sensor (activator) — AMPK (via SIRT1 + direct)
• Atherosclerosis plaque pathology (inhibitor) — endothelial function + SIRT1
• BDNF / TrkB neurotrophic signaling (activator) — BDNF (SIRT1 → CREB)
• Brown adipose thermogenesis (activator) — SIRT1 + AMPK → BAT
• CD4 T-helper differentiation (activator) — SIRT1 → Treg support; ↓Th17
• Cellular senescence / SASP / senolytics (inhibitor) — SIRT1 → SASP modulation
• cGAS-STING cytosolic DNA sensing → type I IFN (inhibitor) — cGAS-STING (anti-inflammatory)
• Circadian clock (activator) — SIRT1 → BMAL1 deacetylation
• Estrogen phase-2 clearance (activator) — phase-2 enzymes + ERα/β partial modulation
• Estrogen receptor (ERα / ERβ / GPER) (activator) — phytoestrogen + SIRT1
• Ferroptosis (inhibitor) — ferroptosis (preclinical antioxidant)
• GSH / GSSG redox cycle (activator) — SIRT1 + Nrf2 → mitochondrial antioxidant defenses
• Hedgehog / Smoothened signaling (inhibitor) — Hh / GLI (preclinical)
• Hepcidin / ferroportin iron regulation (inhibitor) — hepcidin (anti-inflammatory)
• Hippo / YAP-TAZ signaling (inhibitor) — YAP via SIRT1 + AMPK
• Kynurenine pathway (inhibitor) — IDO1 (anti-inflammatory)
• MAPK / ERK (RAS-RAF-MEK-ERK) cascade (inhibitor) — MAPK (SIRT1 + direct)
• Microbiome short-chain fatty acid signaling (activator) — microbiome composition (some SCFA-promoting strains)
• Mitophagy (activator) — SIRT1 → mitochondrial QC
• NAD+ / sirtuin / longevity axis (activator) — SIRT1 + AMPK + Nrf2
• Necroptosis (inhibitor) — necroptosis (SIRT1-mediated)
• Neuroinflammation (inhibitor) — SIRT1 → ↓microglial activation
• Notch signaling (inhibitor) — Notch (chronic)
• Nrf2 / Keap1 antioxidant response (activator) — SIRT1 + Nrf2 + AMPK
• p53 / MDM2 DNA-damage response (activator) — SIRT1 deacetylates p53 — context-dependent; preclinical cancer-suppressive
• Parkinson disease (inhibitor) — α-synuclein aggregation (SIRT1 + direct)
• Pyroptosis (inhibitor) — NLRP3 / SIRT1
• Telomere maintenance + shelterin complex (activator) — SIRT1 → telomere protection (chronic, modest)
• TLR (Toll-like receptor) innate signaling (inhibitor) — TLR4 / NF-κB (SIRT1-mediated)
• Unfolded protein response / ER stress (inhibitor) — ER stress (SIRT1-mediated)
• Wnt / β-catenin canonical signaling (inhibitor) — Wnt (preclinical CRC)

Chemical Identifiers

• PubChem CID: 445154
• Formula: C14H12O3
• Molecular weight: 228.25 g/mol
• InChIKey: LUKBXSAWLPMMSZ-OWOJBTEDSA-N
• SMILES: C1=CC(=CC=C1/C=C/C2=CC(=CC(=C2)O)O)O

References

• PMID 15333514