Schisandrin B attenuates CCl4-induced liver fibrosis in rats by regulation of Nrf2-ARE and TGF-beta/Smad signaling pathways

作者：Chen, Qingshan; Zhang, Hai; Cao, Yan; Li, Ying; Sun, Sen; Zhang, Junping; Zhang, Guoqing^*

来源：Drug Design, Development and Therapy, 2017, 11: 2179-2191.

DOI：10.2147/DDDT.S137507

• schisandrin B
• liver fibrosis
• hepatic stellate cell activation
• Nrf2
• TGF-beta/Smad

Liver fibrosis is a major pathological feature of chronic liver diseases and there is no effective therapy program at present. Schisandrin B (Sch B) is the major bioactive ingredient of Schisandra chinensis, with antioxidative, anti-inflammatory, antitumor, and hepatoprotective properties. This study aimed to investigate the protective effect and related molecular mechanism of Sch B against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. The in vivo therapeutic effect of Sch B on liver fibrosis induced by CCl4 was examined in rats. In vitro, rat hepatic stellate cells (HSC-T6) were used to assess the effect of Sch B on the activation of HSCs. Sch B effectively attenuated liver damage and progression of liver fibrosis in rats, as evidenced by improved liver function and decreased collagen deposition. The effects of Sch B were associated with attenuating oxidative stress by activating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling and suppressing HSC activation by inhibiting the transforming growth factor-beta (TGF-beta)/Smad signaling pathway. In an in vitro study, it was shown that Sch B inhibited TGF-beta-induced HSC activation. Finally, Sch B significantly inhibited TGF-beta 1-stimulated phosphorylation of Smad and signaling of mitogen-activated protein kinases. This study demonstrates that Sch B prevents the progression of liver fibrosis by the regulation of Nrf2-ARE and TGF-beta/Smad signaling pathways, and indicates that Sch B can be used for the treatment of liver fibrosis.

• 出版日期2017
• 单位同济大学; 中国人民解放军第二军医大学