Effects of tanshinone IIA on the hepatotoxicity and gene expression involved in alcoholic liver disease

Hu-Quan Yin, Youn-Su Kim, You-Jin Choi, Youn-Chul Kim, Dong-Hwan Sohn, Shi-Yong Ryu, Byung-Hoon Lee

Tanshinone IIA is one of the most abundant constituents of the root of Salvia miltiorrhiza BUNGE which exerts antioxidant and anti-inflammatory actions in many experimental disease models. In the present study, we demonstrated that the standardized fraction of S. miltiorrhiza (Sm-SF) was able to protect RAW 264.7 cells from ethanol-and lipopolysaccharide (LPS)-induced production of superoxide radical, activation of NADPH oxidase and subsequently death of the cells. Among four main components of Sm-SF, tanshinone IIA was the most potent in protecting cells from LPS-and ethanol-induced cytotoxicity. LPS or ethanol induced the expression of CD14, iNOS, and SCD1 and decreased RXR-alpha, which was completely reversed by tanshinone IIA. In H4IIEC3 cells, 10 microM tanshinone IIA effectively blocked ethanol-induced fat accumulation as evidenced by Nile Red binding assay. These results indicate that tanshinone IIA may have potential to inhibit alcoholic liver disease by reducing LPS-and ethanol-induced Kupffer cell sensitization, inhibiting synthesis of reactive oxygen/nitrogen species, inhibiting fatty acid synthesis and stimulating fatty acid oxidation.