Hemistepsin A (HsA), isolated from Hemistepta lyrata (Bunge) Bunge, has the ability to ameliorate hepatitis in mice. However, the effects of H. lyrata and HsA on other types of liver disease have not been explored. In this report, we investigated the effects of H. lyrata and HsA on liver fibrosis and the underlying molecular mechanisms in activated hepatic stellate cells (HSCs). Based on cell viability-guided isolation, we found HsA was the major natural product responsible for H. lyrata-mediated cytotoxicity in LX-2 cells. HsA significantly decreased the viability of LX-2 cells and primary activated HSCs, increased the binding of Annexin V, and altered the expression of apoptosis-related proteins, suggesting that HsA induces apoptosis in activated HSCs. HsA reduced the phosphorylation of IKKε and the transactivation of nuclear factor-κB (NF-κB). Moreover, HsA decreased the phosphorylation of Akt and its downstream signaling molecules. Transfection experiments suggested that inhibition of NF-κB or Akt is essential for HsA-induced apoptosis of HSCs. In a CCl4-induced liver fibrosis model, HsA administration significantly decreased ALT and AST activities. Furthermore, HsA attenuated CCl4-mediated collagen deposits and profibrogenic genes expression in hepatic tissue. Thus, HsA may serve as a natural product for managing liver fibrosis through inhibition of NF-κB/Akt-dependent signaling.

中文翻译：

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Hemistepsin A通过抑制核因子-κB和Akt来诱导活化的肝星状细胞凋亡，从而减轻肝脏纤维化。

从半边天蛙（Bunge）Bunge分离出的半天蛙蛋白A（HsA）具有改善小鼠肝炎的能力。但是，还没有研究过H. lyrata和HsA对其他类型肝病的影响。在此报告中，我们调查了H. lyrata和HsA对肝纤维化的影响以及激活的肝星状细胞（HSCs）的潜在分子机制。基于细胞活力指导的分离，我们发现HsA是主要的天然产物，负责LX-2细胞中的lyrata介导的细胞毒性。HsA显着降低了LX-2细胞和初级激活的HSC的活力，增加了膜联蛋白V的结合，并改变了凋亡相关蛋白的表达，表明HsA诱导了激活的HSC中的凋亡。HsA减少了IKKε的磷酸化和核因子-κB（NF-κB）的反式激活。此外，HsA降低了Akt及其下游信号分子的磷酸化。转染实验表明，抑制NF-κB或Akt对HsA诱导的HSCs凋亡至关重要。在CCl4诱导的肝纤维化模型中，HsA给药显着降低了ALT和AST活性。此外，HsA减弱了肝组织中CCl4介导的胶原蛋白沉积和profibrogenic基因表达。因此，HsA可以作为天然产物，通过抑制NF-κB/ Akt依赖性信号传导来控制肝纤维化。此外，HsA减弱了肝组织中CCl4介导的胶原蛋白沉积和促纤维化基因的表达。因此，HsA可以作为天然产物，通过抑制NF-κB/ Akt依赖性信号传导来控制肝纤维化。此外，HsA减弱了肝组织中CCl4介导的胶原蛋白沉积和profibrogenic基因表达。因此，HsA可以作为天然产物，通过抑制NF-κB/ Akt依赖性信号传导来控制肝纤维化。