10 Resveratrol

Resveratrol (trans-3, 40, 5-trihydroxystilbene) is a polyphenol found in grapes, peanuts, and mulberries. Resveratrol, produced in response to UV irradiation, fungi, rhizobacteria, etc.,177 has been studied in a wide variety of health areas since the French Paradox was suggested, the French population has a low incidence of cardiovascular diseases although they consume a diet rich in saturated fats.178

Resveratrol inhibits COX-2 and NF-B, thus possesses antiinflammatory properties through inhibition of COX and proinflammatory cytokines (IL-1).179182

The antifibrotic properties of resveratrol were demonstrated in an experimental model of CCl4-induced liver fibrosis by downregulating TGF- and NF-B, and preventing HSC activation.181,183,184 Resveratrol reduces the level of cell cycle protein cyclin D1 in HSC and inhibits the production of TNF- by lipopolysaccharide-stimulated Kupffer cells.185 Besides its immunomodulatory properties, resveratrol possesses antioxidant capacity due to its chemical structure, its OH groups and the delocalization of electrons through the molecule should act as scavengers of free radicals.186 Moreover, resveratrol possesses beneficial effects against acetaminophen-induced damage through its antioxidant properties by preventing GSH depletion.187 As an alternative way of protection from oxidative stress, resveratrol stimulates Nrf2, therefore inhibiting oxidative stress by stimulating the antioxidant enzymatic system.188,189 According to this, resveratrol protects from BDL-induced secondary biliary cirrhosis by preserving liver function and blocking oxidative damage and inflammation; moreover, resveratrol inhibits ductular proliferation resulting in an anticholestatic effect.190

In addition, resveratrol is effective to avoid the novo lipogenesis in different models of hepatic steatosis invitro191; it also reduces the expression of the transcription factor important for lipogenesis, SREBP-1c, in a steatosis induced with palmitate192 and inhibits lipid and triacylglycerol accumulation in HepG2 cells induced by high concentrations of glucose.193,194

Regarding HCC, resveratrol inhibited the formation of hepatocyte nodules by decreasing malignant cell proliferation and enabling apoptosis through reducing Bcl2 increasing Bax expression and decreases hepatic cell proliferation.194 Interestingly, a clinical study demonstrated the ability of resveratrol to induce apoptosis of cancerous cells in patients with colorectal cancer and hepatic metastasis.195 Resveratrol has demonstrated to inhibit the proliferation HepG2 cells in a dose-dependent manner; resveratrol also prevents the cells from entering mitosis and arrests them in the S and G2/M phase.196

In addition, it inhibits the expression of VEGF in HepG2 cells, downregulates NF-B signaling pathways, and overexpresses caveolin-1, which increases apoptosis in a caspase-3 expression and p38 mitogenactivated protein kinase pathway-dependent manner.197199

In summary, resveratrol displays demonstrated antioxidant, antiinflammatory, antisteatotic, and anticancer properties useful in the treatment of various liver disorders.

More:

Resveratrol - an overview | ScienceDirect Topics