Diosgenin ameliorating non‐alcoholic fatty liver disease via Nrf2 ‐mediated regulation of oxidative stress and ferroptosis

作者：Xin Zhang, Guoliang Yin, Suwen Chen, Decheng Meng, Wenfei Yu, Hongshuai Liu, Linya Wang, Fengxia Zhang · 发表于：Diabetes Obesity and Metabolism · 年份：2024 · DOI：10.1111/dom.15945 · 被引用次数：12 · 研究领域：Ferroptosis and cancer prognosis、Phytochemical Studies and Bioactivities、Potato Plant Research

AIM: This study aimed to investigate the mechanisms through which diosgenin inhibits the pathogenesis of non-alcoholic fatty liver disease, focusing particularly on ferroptosis-related pathways and its reliance on nuclear factor erythroid 2-related factor 2. MATERIALS AND METHODS: Using a rat model, we showed diosgenin's efficacy in reducing lipid deposition throughout the body and examined its impact on ferroptosis-related gene expression in vivo. Moreover, in vitro experiments using human hepatocellular liver carcinoma cell line cells were conducted to assess oxidative stress and ferroptosis levels. RESULTS: Diosgenin decreased lipid accumulation and steatosis; lowered serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, glutamic pyruvic transaminase and glutamic oxaloacetic transaminase; reduced interleukin-1β and tumour necrosis factor-α; diosgenin decreased malondialdehyde levels; and increased serum superoxide dismutase levels in a rat model of high-fat diet-induced non-alcoholic fatty liver disease. Diosgenin upregulated the expression of nuclear factor erythroid 2-related factor 2 and its downstream ferroptosis-related genes to inhibit ferroptosis in the livers of rats with non-alcoholic fatty liver disease. Diosgenin decreased reactive oxygen species levels and enhanced the expression of ferroptosis-related genes in human hepatocellular liver carcinoma cells induced by free fatty acids, with its effects being dependent on nuclear fac...