Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China.
Aging (Albany NY). 2020 Feb 5;12(3):2049-2069. doi: 10.18632/aging.102721.
Hepatic steatosis and oxidative stress are considered to be the sequential steps in the development of non-alcoholic fatty liver disease (NAFLD). We previously found that catalpol, an iridoid glucoside extracted from the root of Romania glutinosa L, protected against diabetes-induced hepatic oxidative stress. Here, we found that the increased expression of p66shc was observed in NAFLD models and catalpol could inhibit p66shc expression to ameliorate NAFLD effectively. However, the underlying mechanisms remained unknown. The aim of the present study was to investigate the p66shc-targeting miRNAs in regulating oxidative stress and hepatic steatosis, also the mechanisms of catalpol inhibiting NAFLD. We found that the effects of catalpol inhibiting hepatic oxidative stress and steasis are dependent on inhibiting P66Shc expression. In addition, miR-96-5p was able to suppress p66shc/cytochrome C cascade via targeting p66shc mRNA 3'UTR, and catalpol could lead to suppression of NAFLD via upregulating miR-96-5p level. Thus, catalpol was effective in ameliorating NAFLD, and miR-96-5p/p66shc/cytochrome C cascade might be a potential target.
肝脂肪变性和氧化应激被认为是非酒精性脂肪性肝病 (NAFLD) 发展的连续步骤。我们之前发现，梓醇，一种从罗马尼亚胶质根中提取的环烯醚萜苷，可预防糖尿病引起的肝氧化应激。在这里，我们发现 p66shc 的表达增加在 NAFLD 模型中观察到，梓醇可以抑制 p66shc 的表达，有效地改善 NAFLD。然而，其潜在的机制仍不清楚。本研究的目的是研究针对 p66shc 的 miRNA 在调节氧化应激和肝脂肪变性中的作用，以及梓醇抑制 NAFLD 的机制。我们发现，梓醇抑制肝氧化应激和 steasis 的作用依赖于抑制 P66Shc 的表达。此外，miR-96-5p 能够通过靶向 p66shc mRNA 3'UTR 来抑制 p66shc/细胞色素 C 级联，而梓醇可以通过上调 miR-96-5p 水平来抑制 NAFLD。因此，梓醇在改善 NAFLD 方面是有效的，miR-96-5p/p66shc/细胞色素 C 级联可能是一个潜在的靶点。
