Department of Pharmaceuticals, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; College of Pharmacy, Dalian Medical University, 9 Western Lvshun South Road, Dalian 116044, China.
College of Pharmacy, Dalian Medical University, 9 Western Lvshun South Road, Dalian 116044, China.
Biomed Pharmacother. 2018 Jan;97:481-488. doi: 10.1016/j.biopha.2017.10.153. Epub 2017 Nov 6.
Our previous works showed that dioscin, a natural product, could protect liver from acute liver damages induced by dimethylnitrosamine, ethanol, carbon tetrachloride and acetaminophen. However, the effect of dioscin on thioacetamide (TAA)-induced acute liver injury still remained unknown. The purpose of this study was to investigate whether dioscin confers a protective effect against TAA-induced acute liver injury in rats and mice. The results showed that dioscin decreased the serum levels of ALT, AST, and rehabilitated histopathological changes compared with the model groups. In addition, dioscin obviously increased the levels of GSH, GSH-Px, SOD, and significantly reduced MDA levels compared with the model groups. Mechanistic study showed that dioscin significantly up-regulated the expression levels of FXR, p-AMPKα, and then increased the expression levels of Nrf2, HO-1, NQO-1, GCLM and GST. Furthermore, dioscin obviously down-regulated the expression levels of NF-κB (p65), ICAM-1, HMGB1, COX-2, TNF-α, IL-1β and IL-6. Taken together, dioscin showed protective effect against TAA-induced acute liver injuries in rats and mice and the effects might be obtained through inhibiting oxidative stress and inflammation via FXR/AMPK signal pathway. These findings provided a new insight on the role of doscin in the treatment of acute liver injury.
我们之前的研究表明,薯蓣皂苷元作为一种天然产物,能够保护肝脏免受二甲基亚硝胺、乙醇、四氯化碳和对乙酰氨基酚引起的急性肝损伤。然而,薯蓣皂苷元对硫代乙酰胺(TAA)诱导的急性肝损伤的影响仍不清楚。本研究旨在探讨薯蓣皂苷元是否对 TAA 诱导的大鼠和小鼠急性肝损伤具有保护作用。结果表明,薯蓣皂苷元可降低 ALT、AST 血清水平,并与模型组相比,改善组织病理学变化。此外,薯蓣皂苷元明显增加 GSH、GSH-Px、SOD 的水平,明显降低 MDA 水平与模型组相比。机制研究表明,薯蓣皂苷元显著上调 FXR、p-AMPKα 的表达水平,从而增加 Nrf2、HO-1、NQO-1、GCLM 和 GST 的表达水平。此外,薯蓣皂苷元明显下调 NF-κB(p65)、ICAM-1、HMGB1、COX-2、TNF-α、IL-1β 和 IL-6 的表达水平。综上所述,薯蓣皂苷元对 TAA 诱导的大鼠和小鼠急性肝损伤具有保护作用,其作用可能是通过 FXR/AMPK 信号通路抑制氧化应激和炎症反应来实现的。这些发现为薯蓣皂苷元在急性肝损伤治疗中的作用提供了新的认识。