Protective Effect of Phaleria macrocarpa Water Extract (Proliverenol) against Carbon Tetrachloride-Induced Liver Fibrosis in Rats: Role of TNF- α and TGF- β 1

Phaleria macrocarpa is one of the Indonesian herbal plants which has been shown to have a hepatoprotective effect. This study was conducted to evaluate the protective effect of water extract of mahkota dewa ( Phaleria macrocarpa ) in liver fibrosis and to elucidate its mechanism of action. Male Sprague-Dawley rats were treated with carbon tetrachloride (CCl 4 ) for 8 weeks to induce liver fibrosis. Rats were randomly divided into 6 groups (n=5), i.e., control group, CCl4 group, CCl4 + NAC group, CCl4 + various doses of water extract of Phaleria macrocarpa (50, 100, and 150 mg/kg body weight). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), liver histopathology, malondialdehyde (MDA), ratio GSH/GSSG, Tumor Necrosis Factor- (TNF-) α , and Transforming Growth Factor- (TGF-) β 1 were analyzed . This study demonstrated that water extract of Phaleria macrocarpa and NAC significantly protected CCl 4 -induced liver injury as demonstrated by reduced AST, ALT, ALP, and fibrosis percentage compared with the CCl 4 -only group. In addition, water extract of Phaleria macrocarpa and NAC significantly reduced the levels of MDA, TNF- α , and TGF- β 1 as well as increasing the ratio of GSH/GSSG. Water extract of Phaleria macrocarpa prevents CCl 4 -induced fibrosis in rats. The prevention of liver fibrosis was at least in part through its antioxidant and anti-inflammatory activities and through its capacity to inhibit hepatic stellate cells (HSC) activation by reducing fibrogenic cytokine TGF- β 1 .