Alcoholic hepatitis (AH) has caused serious mortality to the world’s population. Despite tremendous efforts to reduce disease burden, effective treatments for this disease are still lacking. Ginsenoside Rg1 (G-Rg1) has been reported to be hepatoprotective in several liver injury models. However, therapeutic potential of this drug in AH has not been tested. In this study, using a chronic ethanol-feeding model, we found that ethanol-fed mice presented clinical indicators of liver injury, such as elevated serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (Tbil), as well as development of hepatic steatosis. Upon treatment with G-Rg1, animals showed marked decreases in serum biochemical parameters, as well as improvement in liver histology. Mechanistically, G-Rg1 blocked the induction of cytochrome P4502E1 (CYP2E1), and prevented the generation of reactive oxygen species (ROS), mitochondria damage, as well as hepatocellular apoptosis. As a result, NLRP3 inflammasome activation was inhibited, which subsequently suppressed the production of active caspase-1 and inflammatory cytokines. Our data has demonstrated a hepatoprotective role for G-Rg1 in AH, and identified potential drugable pathways to improve disease outcomes. These findings may have significant implications for developing novel therapies for inflammatory liver diseases.

酒精性肝炎（AH）已导致世界人口严重死亡。尽管为减轻疾病负担付出了巨大的努力，但仍缺乏对该疾病的有效治疗方法。人参皂苷Rg1（G-Rg1）在几种肝损伤模型中都有保肝作用。但是，该药物在AH中的治疗潜力尚未得到验证。在这项研究中，我们使用慢性乙醇喂养模型，发现以乙醇喂养的小鼠表现出肝损伤的临床指标，例如血清丙氨酸转氨酶（ALT），天冬氨酸转氨酶（AST）和总胆红素（Tbil）升高，以及肝脂肪变性的发展。用G-Rg1治疗后，动物的血清生化指标明显下降，肝脏组织学也得到改善。机械上，G-Rg1阻止了细胞色素P4502E1（CYP2E1）的诱导，并阻止了活性氧（ROS）的产生，线粒体损伤以及肝细胞凋亡。结果，NLRP3炎性体激活被抑制，随后抑制了活性caspase-1和炎性细胞因子的产生。我们的数据证明了G-Rg1在AH中具有保肝作用，并确定了改善疾病预后的潜在药物途径。这些发现可能对开发用于炎症性肝病的新疗法具有重要意义。随后抑制了活性caspase-1和炎性细胞因子的产生。我们的数据证明了G-Rg1在AH中具有保肝作用，并确定了改善疾病预后的潜在药物途径。这些发现可能对开发用于炎症性肝病的新疗法具有重要意义。随后抑制了活性caspase-1和炎性细胞因子的产生。我们的数据证明了G-Rg1在AH中具有保肝作用，并确定了改善疾病预后的潜在药物途径。这些发现可能对开发用于炎症性肝病的新疗法具有重要意义。