Department of General Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Biochemistry (Mosc). 2021 Nov;86(11):1407-1417. doi: 10.1134/S0006297921110055.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Therapeutic activity of icariin, a major bioactive component of Epimedii Herba, in NAFLD is still unknown. Herein, the C57BL/6J mice were fed with a high-fat diet for 16 weeks to establish a NAFLD model. Mice were assigned to five groups: control group, NAFLD group, and icariin treatment groups. Effects of icariin on blood indices, glucose tolerance, insulin sensitivity, histopathological morphology, cell apoptosis, lipid accumulation, and AMPK signaling were analyzed. In addition, another cohort of mice were assigned to five groups: control group, NAFLD group, dorsomorphin treatment group, icariin treatment group, and dorsomorphin + icariin treatment group. Expression of proteins in liver tissues associated with AMPK signaling, and levels of ALT and AST were evaluated. Icariin attenuated the NAFLD-induced increase of the TG, TC, LDL-C, ALT, AST levels. HDL-C levels were affected neither by NAFLD nor by icariin. Furthermore, icariin treatment (100-200 mg/kg) counteracted the NAFLD-reduced glucose tolerance and insulin sensitivity and modulated histopathological changes, cell apoptosis, and lipid accumulation in liver tissues. Additionally, icariin mitigated the NAFLD-induced up-regulation of the cleaved caspase 3/9, SREBP-1c, and DGAT-2 levels, and enhanced the expression level of CPT-1, p-ACC/ACC, AMPKα1, PGC-1α, and GLUT4. Effects of icariin on the AMPK signaling and levels of AST and ALT could be reversed by AMPK inhibitor, dorsomorphin. This paper investigates the glucose-reducing and lipid-lowering effects of icariin in NAFLD. Moreover, icariin might function through activating the AMPKα1/PGC-1α/GLTU4 pathway.
非酒精性脂肪性肝病 (NAFLD) 是世界上最常见的肝脏疾病。淫羊藿的主要生物活性成分之一淫羊藿苷在 NAFLD 中的治疗活性尚不清楚。本研究采用高脂饮食喂养 C57BL/6J 小鼠 16 周建立 NAFLD 模型。将小鼠分为 5 组：对照组、NAFLD 组和淫羊藿苷治疗组。分析淫羊藿苷对血液指标、葡萄糖耐量、胰岛素敏感性、组织病理学形态、细胞凋亡、脂质积累和 AMPK 信号的影响。此外，另一组小鼠分为 5 组：对照组、NAFLD 组、多西环素治疗组、淫羊藿苷治疗组和多西环素+淫羊藿苷治疗组。评估与 AMPK 信号相关的肝组织蛋白表达及 ALT 和 AST 水平。淫羊藿苷可减轻 NAFLD 引起的 TG、TC、LDL-C、ALT 和 AST 水平升高。HDL-C 水平既不受 NAFLD 影响，也不受淫羊藿苷影响。此外，淫羊藿苷治疗（100-200mg/kg）可对抗 NAFLD 降低的葡萄糖耐量和胰岛素敏感性，并调节肝组织的组织病理学变化、细胞凋亡和脂质积累。此外，淫羊藿苷可减轻 NAFLD 诱导的 cleaved caspase 3/9、SREBP-1c 和 DGAT-2 水平上调，并增强 CPT-1、p-ACC/ACC、AMPKα1、PGC-1α 和 GLUT4 的表达水平。AMPK 抑制剂多西环素可逆转淫羊藿苷对 AMPK 信号和 AST、ALT 水平的影响。本文研究了淫羊藿苷在 NAFLD 中的降血糖和降血脂作用。此外，淫羊藿苷可能通过激活 AMPKα1/PGC-1α/GLUT4 通路发挥作用。
