Acute liver failure (ALF) is a dramatic liver disease characterized by large areas of inflammation. However, there are no available effective targeted drugs for ALF treatment. In the study, serum biochemical index and H&E were used to explore the amelioration of the liver histopathological changes. The oxidative stress kits, quantitative real-time PCR, western blot, immunohistochemistry, immunofluorescence staining, reactive oxygen species (ROS), and siRNA were used to elucidate the mechanisms underlying isoliquiritigenin (ISL) protection. The results showed that ISL significantly improved the liver pathological changes. Furthermore, ISL reduced oxidative stress by altering the expression of PGC-1α, Nrf2, HO-1, NQO1, Keap1, GCLC, and GCLM in damaged hepatocytes. Moreover, the levels of inflammation-related genes including NLRP3 inflammasome, IL-1β, IL-6, TNF-α, iNOS, and Mip-2 were repressed by ISL. In addition, ISL alleviated LPS/D-GalN-induced hepatocytes apoptosis by increasing the Bcl-2/Bax ratio and suppressing the expression of cleaved caspase-3. Further in vivo and in vitro evidence proved the involvement of the PGC-1α/Nrf2 signaling pathway in ISL protection. In conclusion, ISL improves the ability of anti-oxidative stress, alleviates inflammatory reaction, apoptosis, and inhibits NLRP3 inflammasome to protect lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALF through activating the PGC-1α/Nrf2 pathway, which provides the possibility for the treatment of ALF.

急性肝功能衰竭 (ALF) 是一种以大面积炎症为特征的严重肝病。然而，目前尚无有效的治疗 ALF 的靶向药物。本研究采用血清生化指标和 H&E 探讨肝脏组织病理学改变的改善情况。氧化应激试剂盒、定量实时 PCR、蛋白质印迹、免疫组织化学、免疫荧光染色、活性氧 (ROS) 和 siRNA 用于阐明异甘草素 (ISL) 保护的机制。结果表明，ISL显着改善了肝脏病变。此外，ISL 通过改变受损肝细胞中 PGC-1α、Nrf2、HO-1、NQO1、Keap1、GCLC 和 GCLM 的表达来降低氧化应激。此外，炎症相关基因的水平，包括 NLRP3 炎症小体，ISL 抑制 IL-1β、IL-6、TNF-α、iNOS 和 Mip-2。此外，ISL 通过增加 Bcl-2/Bax 比率和抑制裂解的 caspase-3 的表达来减轻 LPS/D-GalN 诱导的肝细胞凋亡。更远体内和体外证据证明 PGC-1α/Nrf2 信号通路参与 ISL 保护。总之，ISL通过激活PGC-1α/Nrf2通路，提高抗氧化应激能力，减轻炎症反应、细胞凋亡，抑制NLRP3炎症小体保护脂多糖/D-半乳糖胺（LPS/D-GalN）诱导的ALF，为 ALF 的治疗提供了可能。