Inhibitory effect of tetrahydrocurcumin on dimethylnitrosamine-induced liver fibrosis in rats

Chronic liver disease is characterized by an exacerbated accumulation of deposition of collagen, causing progressive fibrosis, which may lead to cirrhosis. We evaluated the inhibitory effect of tetrahydrocurcumin (THC), a major metabolite of curcumin, on liver fibrogenesis both in vitro, HSC-T6 cell, and in vivo, dimethylnitrosamine (DMN)-induced liver fibrosis in rat. The liver inflammation in HSC-T6 cell was initiated by transforming growth factor-β1 (TGF-β1), and fibrosis in Sprague-Dawley rats was induced by intraperitoneal (i.p.) injection of DMN (10 mg/kg) 3 days per week for four consecutive weeks. THC (10 mg/kg) was administered in rats by oral gavage daily. DMN caused hepatic injury as indicated by analysis of liver function, morphology, histochemistry, and fibrotic parameters. Once-daily dosing with THC alleviated liver damage as signified by histopathological examination of the α-smooth muscle actin (α-SMA) and collagen I, accompanied by the reduction TGF-β1 and serum levels of transaminase (P < 0.05). These data revealed that the THC exerts hepatoprotective activity in experimental fibrosis, potentially by inhibiting the TGF-β1/Smad signaling.