Hepatoprotective activities of the methanol extract of Angelica shikokiana and isoepoxypteryxin against hepatocellular carcinoma

Angelica shikokiana (Apiaceae) is a Japanese traditional herb and widely marketed as a dietary food supplement as a health tea preparation consumed as a daily beverage for its health benefits. Our previous research showed that the methanol extract of the aerial parts of A. shikokiana and its major coumarin, isoepoxypteryxin had a significant cytotoxicity against HepG2 cell line. In this study, we investigated the hepatoprotective activity more deeply by the in vitro inhibition of HepG2 cells invasion assay and in vivo using thioacetamide-induced hepatocellular carcinoma model in rats. The ex vivo levels of nitric oxide production, inducible nitric oxide synthase, vascular endothelial cell growth factor-C and caspase-3 were also estimated to investigate the possible mechanisms of hepatoprotection. The methanol extract of A. shikokiana and isoepoxypteryxin concentration-dependently depressed the invasion of HepG2 cells induced by 12-O-tetradecanoylphorbol 13-acetate. In vivo, they significantly reduced the levels of alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase, total bilirubin and nitric oxide production when compared with hepatocellular carcinoma group. Besides, the thioacetamide-injected groups treated with methanol extract of A. shikokiana and isoepoxypteryxin exhibited a significant increase in the level of caspase-3 protein and a significant decrease of inducible nitric oxide synthase and vascular endothelial cell growth factor C levels when compared with hepatocellular carcinoma group. To the best of our knowledge, this is the first report of the hepatoprotective effect of A. shikokiana and isoepoxypteryxin against hepatocellular carcinoma.