Polyphenols are found in many plant foods that have health-promoting effects. Resveratrol is a natural polyphenol compound found in foods such as grapes, peanuts, blueberries, and red wine. Resveratrol supplementation has been studied for over thirty years. Many studies highlight its importance in slowing aging through suppressing oxidative stress, inhibiting inflammatory response, improving mitochondrial function, and altering cell death.
There exist two structurally distinct forms of resveratrol, namely cis- and trans-resveratrol. The predominant form of resveratrol in grapes and grape juice is trans-resveratrol. Toxicological data confirm that RVT is well tolerated. Any adverse effects (mainly concerning the abdomen), at doses of ≥ 500 mg/day for long periods, remain moderate and reversible.
Resveratrol is well absorbed (~75%), primarily through transepithelial diffusion, by humans when taken orally, its bioavailability is relatively low (<1%) due to its rapid metabolism in the intestine and liver into various metabolites. Maximum concentration is typically within one hour. Studies have demonstrated that even low concentrations of resveratrol have biologic activity.
Resveratrol can inhibit human platelet aggregation in vitro. Theoretically, high intakes of resveratrol could increase the risk of bruising and bleeding when taken with anticoagulant drugs, antiplatelet drugs, and non-steroidal anti-inflammatory drugs.
Cytochrome P450 3A4 (CYP3A4) is one of the most abundant CYP isoform enzymes, which catalyzes metabolism of most of the drugs available in the market affecting clearance and toxicity of the drug. Resveratrol has been shown to inhibit CYP3A4 activity in vitro and in healthy volunteers.
Resveratrol's main biological activity effects, and plausible mechanisms of action are demonstrated in different in vitro and in vivo conditions.
| Biologic Activity | Effect |
Plausible Mechanism(s)
|
| Anti-Proliferative | Induction of apoptosis and/or cell cycle arrest |
Caspase activation, inhibition of Bcl-2 proteins, PI3K/Akt/mTOR pathway, modulation of cyclins and cyclin-dependent kinases balance
|
| Anti-Angiogenesis | Inhibition of tumor growth, cell migration, invasion and metastasis |
Decreases expression of leukotriene B4 and matrix metalloproteinases (particularly, MMP9)
|
| Anti-oxidative | Inhibition of reactive oxygen species (ROS) |
Induction of superoxide dismutase, catalase, & glutathione peroxidase-1
|
| Endothelial | Increased activity and/or expression of endothelial nitric oxide synthase (eNOS) |
via 5'-adenosine monophosphate activated protein kinase (AMPK) or extracellular signal-regulated kinase 1/2 (ERK 1/2-mediated phosphorylation); activating histone/protein deacetylase silent information regulator 2/sirutin 1 (SIRT1)
|
| Anti-Inflammatory (DNA) | Attenuated DNA damage and upregulation of IL-6, TNF-a |
Via SIRT1 activation
|
| Anti-Inflammatory (Extravasation) | Reducing expression of integrin adhesion molecules (ICAM-1 and VCAM-1) |
Inhibition of p38 MAPK signaling pathway
|
| Anti-platelet | Inhibition of platelet activation and aggregation |
Inhibition of p38 MAPK pathway and activation of NO/cyclic guanosine monophosphate causing inhibition of phospholipase C and/or protein kinase C activation
|
| Pro-proliferative and neurogenesis | Inhibition of apoptosis, inflammation and oxidative stress; enhances neuronal cell survival and improves cognitive behavior |
Regulation of HO-1 and peroxisome proliferator activated gamma coactivator 1 alpha (PGC-1a)
|
References:
- Cottart CH, Nivet-Antoine V, Beaudeux JL. Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans. Mol Nutr Food Res. 2014 Jan;58(1):7-21. doi: 10.1002/mnfr.201200589. Epub 2013 Jun 6. PMID: 23740855.
- Wallerath T, Deckert G, Ternes T, Anderson H, Li H, Witte K, Förstermann U. Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation. 2002 Sep 24;106(13):1652-8. doi: 10.1161/01.cir.0000029925.18593.5c. PMID: 12270858.
- Bertelli AA, Giovannini L, Giannessi D, Migliori M, Bernini W, Fregoni M, Bertelli A. Antiplatelet activity of synthetic and natural resveratrol in red wine. Int J Tissue React. 1995;17(1):1-3. PMID: 7499059.
