Inonotsuoxide B suppresses hepatic stellate cell activation and proliferation via the PI3K/AKT and ERK1/2 pathway

Hepatic stellate cells (HSCs) serve a pivotal role in the formation and degradation of the extracellular matrix during liver fibrosis. Inonotsuoxide B is a tetracyclic triterpenoid that can be extracted from Inonotus obliquus and has been previously reported to inhibit the growth of liver and gastric cancer cells. However, its effect on liver fibrosis remain poorly understood. Therefore, in the present study, the potential antiproliferative effects of inonotsuoxide B on HSCs was investigated. Initially, cells were divided into the following five groups: Control; platelet-derived growth factor (PDGF)-BB (10 ng/ml); and PDGF-BB + inonotsuoxide B (5, 10 and 20 mu g/ml) groups. Inonotsuoxide B treatment (5, 10 and 20 mu g/ml) was revealed to reverse PDGF-BB-induced HSC proliferation. Furthermore, the protein expression of alpha-smooth-muscle actin (alpha-SMA) and type I collagen was significantly decreased in the inonotsuoxide B (10 and 20 mu g/ml) groups compared with the PDGF-BB group. Inonotsuoxide B (5, 10 and 20 mu g/ml) was also revealed to suppress PDGF-BB-induced alpha-SMA mRNA expression and activation of the PI3K/AKT and ERK signaling pathways in HSCs. These findings suggest that inonotsuoxide B suppresses the proliferation and activation of HSCs by inhibiting the PI3K/AKT and ERK1/2 signaling pathways.