Experimental and clinical evidence show that liver fibrosis is potentially reversible. Hepatic stellate cells (HSCs) play a key role in the development of liver fibrosis. Some studies have shown that reversine could induce cell apoptosis. We attempted to elucidate the effect of reversine on cell cycle, apoptosis, and activation of HSCs. Data showed that reversine induced morphological changes in HSCs, inhibited cell proliferation, and induced cell-cycle arrest at the G2/M phase. Reversine induced cell apoptosis through caspase-dependent and mitochondria-dependent pathways. Reversine inhibited the activation of HSCs through TGF-β signaling pathway and degraded extracellular matrix protein collagen-I. The decreased TIMP1 and TGF-β proteins promoted fibrosis reversion. Reversine might be a promising drug for liver fibrosis reversion because it induces HSCs apoptosis, restrains cell proliferation, reduces HSCs activation, and degrades extracellular matrix in vitro.

This study investigated the anti-fibrotic effects of reversine and Chinese medicine Xiang–Sha–Liu–Jun–Zi decoction (XSLJZD) on thioacetamide (TAA)-induced hepatic injury. Sprague-Dawley rats were intraperitoneally administered with TAA, then injected with reversine intraperitoneally, and/or orally provided with XSLJZD. TAA resulted in liver injury with increases in the liver index and levels of serum aspartate aminotransferase (AST) and alanine aminotransferase. Reversine alleviated the liver index and AST level and improved TAA-induced pathological changes but decreased TAA-induced collagen deposition, and α-smooth muscle actin and transforming growth factor-β1 expression. Reversine also modulated the mRNA levels of inflammatory cytokines, such as RelA, interleukin (IL)-17A, IL-22, IL-1β, IL-6, NLR family pyrin domain containing 3, platelet-derived growth factor, and monocyte chemoattractant protein, and suppressed nuclear factor (NF)-κB (p65) phosphorylation and caspase 1 activation. Meanwhile, XSLJZD protected TAA-injured liver without increasing fibrosis and enhanced the regulating effect of reversine on RelA, IL-17A, IL-1β, and MCP-1 cytokines. In conclusion, reversine ameliorates liver injury and inhibits inflammation reaction by regulating NF-κB, and XSLJZD protects the liver through its synergistic effect with reversine on regulating inflammatory cytokines.