Inhibitory effects of oxyresveratrol on ERK and Smad1/2 phosphorylation and HSC activation in preventing carbon tetrachloride-induced rat liver fibrosis

Abstract

Oxyresveratrol (ORes, trans-2,4,3′,5′-tetrahydroxy stilbene) naturally exists in mulberry, grapes, peanuts and other plants. It belongs to stilbene polyphenolic family and has an extra hydroxyl group at 2-position comparing with resveratrol (Res). Hence, ORes has stronger antioxidant activity than resveratrol. In present study, we employed a rat hepatic fibrosis model induced by carbon tetrachloride (CCl4) and administrated ORes via gavage feeding to study the protective effects and potential mechanisms of ORes against hepatic fibrosis. We demonstrated that rat liver oxidative damage induced by CCl4 was significantly alleviated after ORes feeding. Furthermore, the mRNA transcription levels of α-smooth muscle actinn (α-SMA), desmin, and two MMPs (MMP2 and MMP9) were reduced and the expression levels of transforming growth factor β1 (TGF-β1), p- small mother against decapen-taplegic protein (Smad)1/2 and p-extracellular signal-regulated kinases (ERK)1/2 in the liver tissue down-regulated dramatically. In a parallel study with Res, ORes showed more efficacious protective effect than Res against rat liver fibrosis, which is attributed to extended conjugation system due to the extra hydroxyl group at 2-position on ORes making it more electron-rich and susceptible to oxidation than Res. Therefore, dietary consumption of mulberry and other fruits containing ORes may be beneficial in the prevention of liver fibrosis.

Keywords

• Oxyresveratrol
• Hepatic fibrosis
• Oxidative stress
• TGF-β/Smad/ERK signaling pathway