Hepatoprotective effects of geniposide in a rat model of nonalcoholic steatohepatitis

Objectives Nonalcoholic steatohepatitis (NASH), a metabolic disorder of the liver, may gradually evolve into fibrosis or cirrhosis. Recent studies have suggested that geniposide can effectively inhibit experimental liver fibrosis. Therefore, the aim of this study was to determine whether geniposide can influence the early phase of fibrogenesis in an animal model of NASH. Methods Male Sprague-Dawley rats were given a high fat diet alone or the same diet combined with geniposide at doses of 25, 50 or 100 mg/kg for six weeks. Ten rats received corresponding solvent as a normal control. Key findings Treatment with geniposide could improve liver histology through reducing the elevated liver index (liver weight/body weight), serum alanine aminotransferase and aspartate aminotransferase. Total cholesterol, triglycerides and free fatty acids in serum and liver decreased in geniposide-treated rats. Furthermore, geniposide increased serum insulin levels but reduced serum tumour necrosis factor-alpha level in high-fat diet rats. In addition, geniposide suppressed expression of CYP2E1 and increased peroxisome proliferator-activated receptor-alpha (PPAR alpha) expression. These benefits may be associated with increased superoxide dismutase and decreased malondialdehyde in liver. Conclusions Geniposide exerts protective effects against hepatic steatosis in rats fed with a high fat diet; the underlying mechanism may be associated with its antioxidant actions or regulation of adipocytokine release and expression of PPAR alpha.