Alisol A 24-acetate (AA), a natural triterpenoid isolated from the traditional Chinese medicine Rhizoma Alismatis, has various therapeutic effects. We investigated the anti-nonalcoholic steatohepatitis (NASH) effect of AA and its underlying mechanisms in vitro and in vivo. C57BL/6 mice were fed a methionine and choline-deficient (MCD) diet for 4 weeks to induce NASH. The mice were simultaneously treated with a daily dose of AA (15, 30, and 60 mg kg⁻¹, ig) for 4 weeks. On the last day, the animals were sacrificed and plasma and liver tissue were collected. Serum and liver tissue biochemical analyses and histological observation were performed. The human hepatic stellate cell line LX-2 was used to build NASH models by culturing with conditioned medium from WRL-68 liver cells after exposure to MCD medium in vitro. Liver oxidative stress and inflammatory indices and autophagy markers were examined. The results showed that AA suppressed reactive oxygen species (ROS) and inflammation in a NASH mouse model and inhibited the expression of inflammatory cytokines and ROS in LX-2 cells in MCD medium. Furthermore, we found AA stimulated autophagy in mice liver and LX-2, which could be the underlying mechanism of AA in NASH. To further investigate the role of autophagy in LX-2 cells, we found that AA regulated autophagy via the AMPK/mTOR/ULK1 pathway and dorsomorphin, a selective AMPK inhibitor, led to the suppression of AA-induced autophagy. Taken together, our results indicate that AA could be a possible therapy for NASH by inhibiting oxidative stress and stimulating autophagy.

Alisol A 24-solate（AA），一种从传统中药Rhizoma Alismatis分离得到的天然三萜类化合物，具有多种治疗作用。我们在体外和体内研究了AA的抗非酒精性脂肪性肝炎（NASH）的作用及其潜在机制。给C57BL / 6小鼠喂食甲硫氨酸和胆碱缺乏（MCD）饮食4周，以诱导NASH。小鼠同时接受日剂量AA（15、30和60 mg kg ^-1，ig）4周。在最后一天，处死动物并收集血浆和肝组织。进行血清和肝组织生化分析和组织学观察。在体外暴露于MCD培养基后，通过与WRL-68肝细胞的条件培养基一起培养，使用人类肝星状细胞系LX-2建立NASH模型。检查了肝脏的氧化应激和炎症指标以及自噬标记。结果表明，AA抑制了NASH小鼠模型中的活性氧（ROS）和炎症，并抑制了MCD培养基中LX-2细胞中炎性细胞因子和ROS的表达。此外，我们发现AA刺激小鼠肝脏和LX-2的自噬，这可能是NASH中AA的潜在机制。为了进一步研究自噬在LX-2细胞中的作用，我们发现AA通过AMPK / mTOR / ULK1途径和自体吗啡（一种选择性的AMPK抑制剂）调节自噬，从而抑制了AA诱导的自噬。两者合计，我们的结果表明，通过抑制氧化应激和刺激自噬，AA可能是NASH的一种可能疗法。