Babao Dan attenuates hepatic fibrosis by inhibiting hepatic stellate cells activation and proliferation via TLR4 signaling pathway

// Lei Liang 1, 2, * , Xue Yang 1, * , Yang Yu 1, 3, * , Xiaoyong Li 1, 2 , Yechen Wu 1, 2 , Rongyu Shi 1 , Jinghua Jiang 1 , Lu Gao 1 , Fei Ye 1 , Qiudong Zhao 1 , Rong Li 1 , Lixin Wei 1 , Zhipeng Han 1 1 Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China 2 Medical College of Soochow University, Suzhou, China 3 Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200065, China * These authors contributed equally to this work Correspondence to: Zhipeng Han, email: hanzhipeng0311@126.com Lixin Wei, email: weilixin_smmu@163.com Keywords: hepatic fibrosis, hepatic stellate cells, chinese medicine, Babao Dan, toll-like receptor 4 Received: August 01, 2016 Accepted: October 12, 2016 Published: October 20, 2016 ABSTRACT Babao Dan (BBD), a traditional Chinese medicine, has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the protective effect of BBD on rat hepatic fibrosis induced by diethylnitrosamine (DEN) and explore it possible mechanism. BBD was administrated while DEN was given. After eight weeks, values of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) indicated that BBD significantly protected liver from damaging by DEN and had no obvious side effect on normal rat livers. Meanwhile, BBD attenuated hepatic inflammation and fibrosis in DEN-induced rat livers through histopathological examination and hepatic hydroxyproline content. Furthermore, we found that BBD inhibited hepatic stellate cells activation and proliferation without altering the concentration of lipopolysaccharide (LPS) in portal vein. In vitro study, serum from BBD treated rats (BBD-serum) could also significantly suppress LPS-induced HSCs activation through TLR4/NF-κB pathway. In addition, BBD-serum also inhibited the proliferation of HSCs by regulating TLR4/ERK pathway. Our study demonstrated that BBD may provide a new therapy strategy of hepatic injury and hepatic fibrosis.