Ginsenoside Re ameliorates thioacetamide-induced acute liver injury through inhibiting autophagy-NLRP3 inflammasome pathway

作者：Jing‐Jer Lin, Huan Wang, Ruowei Zhao, Shaohua Li, Dennis Chang, Yanfang Zheng, Xian Zhou, Rui Huang, Mingqing Huang · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1592203 · 被引用次数：7 · 研究领域：Autophagy in Disease and Therapy、Inflammasome and immune disorders、Ginseng Biological Effects and Applications

Background: Ginsenoside Re (G-Re), a unique ginsenoside almost exclusively found in Araliaceae plants, is a promising therapeutic agent for attenuating liver injury. This study aims to investigate the liver-protective effects of G-Re and the underlying mechanisms in acute liver injury models. Methods: Male C57BL/6 mice were intraperitoneally injected with various agents induce the acute liver injury model after pre-treatment with G-Re (5-20 mg/kg, oral gavage). Additionally, the phosphoinositide 3-kinases (PI3K) inhibitor LY294002 and the mammalian target of rapamycin (mTOR) inhibitor RAPA were co-administered with G-Re in the thioacetamide (TAA)-induced rat hepatic stellate cell line (HSC-T6) to explore the mechanisms associated with G-Re. Results: studies consistently showed that G-Re decreased mRNA expression levels of key pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Additionally, G-Re dose-dependently downregulated the protein expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase -1 (caspase-1), interleukin-18 (IL-18), and IL-1β. In addition, our results suggested that the suppression of autophagy by G-Re may play a crucial role in its ability to inhibit the NLRP3 inflammasome. Notably, this regulatory effect on autophagy appears to be mediated through the phosphatidylinositide 3-kinases/protein kinase B/mammalian targ...