Salidroside alleviates lipotoxicity-induced cell death through inhibition of TLR4/MAPKs pathway, and independently of AMPK and autophagy in AML-12 mouse hepatocytes. (February 2020)

• Record Type: Journal Article
• Authors: Dou, Xiaobing; Ding, Qinchao; Lai, Shanglei; Jiang, Fusheng; Song, Qing; Zhao, Xindi; Fu, Ai; Moustaid-Moussa, Naima; Su, Dongju; Li, Songtao
• Is Part Of: Journal of functional foods. Volume 65(2020)
• Publication Date: 2020-02
• Subjects: Salidroside -- Lipotoxicity -- TLR4 -- MAPK -- Hepatocytes; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2019.103691
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Salidroside alleviates hepatocellular death in response to lipotoxicity. Salidroside inhibits lipotoxicity-induced oxidative stress and mitochondrial injury. Salidroside improves lipotoxicity-induced inflammation in hepatocytes. Salidroside inhibits lipotoxicity-activated TLR4/MAPKs pathways in hepatocytes. TLR4 inhibition contributes to salidroside-reduced lipids deposition in hepatocytes. Abstract: Lipotoxicity plays a detrimental role in the pathogenesis of non-alcoholic fatty liver diseases (NAFLD). Salidroside (Sal), a phenylpropanoid glycoside extracted from Rhodiola rosea L, conferred resistance to high-fat diet-induced liver injury. However, the underlying mechanisms are still unclear. This study aimed at investigating Sal-inhibited lipotoxicity and clarify its potential mechanisms. Our study indicated that Sal significantly reversed palmitic acids-induced injury in dose-dependent manner in AML-12 mouse hepatocytes, accompanied with improvement of oxidative stress and mitochondrial damage. Mechanistic analysis revealed that Sal protected hepatic lipotoxicity via reversing TLR4/MAPKs (including JNK, p38, and ERk1/2) and p53 activation, independent from autophagy, AMPK, and Akt pathways. Moreover, TLR4 inhibition also contributed to salidroside-reduced lipids deposition. In sum, this research clearly demonstrated the protective effects of Sal against lipotoxicity-induced hepatic cell death, which was mediated by downregulation of TLR4/MAPKs pathways in hepatocytes. We conclude that Sal is a potential candidate for the treatment of NAFLD.