Silibinin alleviates acute liver failure by modulating AKT/GSK3β/Nrf2/GPX4 pathway

被引:3
作者
Li, Yue [1 ]
Li, Hailan [1 ]
Sun, Minhui [2 ]
Chen, Hong [1 ]
Xiao, Yao [1 ]
Wang, Jieman [1 ]
Zhang, Yuanyuan [1 ]
Fang, Shuhua [3 ]
Kou, Junping [1 ]
机构
[1] China Pharmaceut Univ, Sch Tradit Chinese Pharm, Dept Chinese Mat Med, Jiangsu Key Lab TCM Evaluat & Translat Res, 639 Longmian Rd, Nanjing 211198, Peoples R China
[2] China Pharmaceut Univ, Publ Lab Platform, Nanjing 211198, Jiangsu, Peoples R China
[3] Southeast Univ, Nanjing Lishui Peoples Hosp, Zhongda Hosp, Dept Pharm,Lishui Branch, Nanjing 211200, Peoples R China
关键词
Silibinin Megulmin; Acute liver failure; AKT/GSK3; beta/Nrf2/GPX4; pathway; Ferroptosis; Oxidative stress; Antioxidants; FIBROSIS; MICE;
D O I
10.1007/s00210-024-03760-x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Silibinin (Sil) is a major bioactive component of silymarin, extracted from the fruit and seeds of Silybum marianum. Silibinin meglumine (SM) is a water-soluble derivative of silibinin that has shown significant potential in liver fibrosis. However, the potential effects and underlying mechanisms of SM on acute liver failure (ALF) are still not fully understood. This study aims to find the likely mechanism. An ALF mouse model and a cell model were established with GalN/LPS. SM was administered to mice via the tail vein or to a hepatocyte line (alpha mouse liver 12, AML12). The results showed that SM particularly lowered the mortality and improved liver pathological lesions in ALF mice. Meanwhile, SM improved the levels of GSH, SOD, TNF-alpha, IL-6, IL-1 beta, and IL-10 in the liver tissues and serum. Additionally, SM enhanced cell viability and reduced oxidative stress in vitro. In the AKT/GSK3 beta/Nrf2/GPX4 pathway, the subpathway of AKT/GSK3 beta was inhibited, and the subpathway of Nrf2/GPX4 was activated by SM both in vivo and in vitro. In addition, ferrostatin-1, a ferroptosis inhibitor, and the silencing of AKT using siRNA weakened the protective effect of SM, indicating that this process is mediated in an AKT-dependent manner. All the results suggested that SM inhibits inflammation and oxidative stress by modulating the AKT/GSK3 beta/Nrf2/GPX4 pathway.
引用
收藏
页码:7625 / 7639
页数:15
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