Swertiamarin ameliorates carbon tetrachloride-induced hepatic apoptosis via blocking the PI3K/Akt pathway in rats

Abstract

Swertiamarin (STM) is an iridoid compound that is present in the Gentianaceae swertia genus. Here we investigated antiapoptotic effects of STM on carbon tetrachloride (CCl 4 )-induced liver injury and its possible mechanisms. Adult male Sprague Dawley rats were randomly divided into a control group, an STM 200 mg/kg group, a CCl 4 group, a CCl 4 +STM 100 mg/kg group, and a CCl 4 +STM 200 mg/kg group. Rats in experimental groups were subcutaneously injected with 40% CCl 4 twice weekly for 8 weeks. STM (100 and 200 mg/kg per day) was orally given to experimental rats by gavage for 8 consecutive weeks. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of Bcl-2, Bax, and cleaved caspase-3 proteins were evaluated by western blot analysis. The expression of TGF-1, collagen I, collagen III, CTGF and fibronectin mRNA were estimated by qRT-PCR. The results showed that STM significantly reduced the number of TUNEL-positive cells compared with the CCl 4 group. The levels of Bax and cleaved caspase-3 proteins, and TGF-1, collagen I, collagen III, CTGF, and fibronectin mRNA were significantly reduced by STM compared with the CCl 4 group. In addition, STM markedly abrogated the repression of Bcl-2 by CCl 4 . STM also attenuated the activation of the PI3K/Akt pathway in the liver. These results suggested that STM ameliorated CCl 4 -induced hepatocyte apoptosis in rats.