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Astragaloside IV reverses simvastatin-induced skeletal muscle injury by activating the AMPK-PGC-1α signalling pathway.

Authors :
Jiang, Bing
Yang, Yu‐Jiao
Dang, Wen‐Zhen
Li, Hui
Feng, Gui‐Ze
Yu, Xiao‐Chen
Shen, Xiao‐Yan
Hu, Xu‐Guang
Yang, Yu-Jiao
Dang, Wen-Zhen
Feng, Gui-Ze
Yu, Xiao-Chen
Shen, Xiao-Yan
Hu, Xu-Guang
Source :
Phytotherapy Research; May2020, Vol. 34 Issue 5, p1175-1184, 10p
Publication Year :
2020

Abstract

In this study, we investigated the effect of astragaloside IV on skeletal muscle energy metabolism disorder caused by statins and explored the possible mechanisms. High-fat diet-fed apolipoprotein E knockout (ApoE-/- ) mice performed aerobic exercise and were administered simvastatin, simvastatin + trimetazidine, or simvastatin + astragaloside IV by gavage. At the end of treatment, exercise performance was assessed by the hanging grid test, forelimb grip test, and running tolerance test. Moreover, plasma lipid and creatine kinase concentrations were measured. After sacrifice, the gastrocnemius muscle was used to assess muscle morphology, and energy metabolism was evaluated by determining the concentration of lactic acid and the storage capacity of adenosine triphosphate and glycogen. Mitochondrial function was assessed by measuring mitochondrial complex III and citrate synthase activity and membrane potential. In addition, oxidative stress was assessed by determining the level of hydrogen peroxide. Finally, using western blotting and reverse transcription polymerase chain reaction, we explored the mechanism of astragaloside IV in alleviating simvastatin-induced muscle injury. Our results demonstrated that astragaloside IV reversed simvastatin-induced muscle injury without affecting the lipid-lowering effect of simvastatin. Moreover, astragaloside IV promoted the phosphorylation of AMPK and activated PGC-1α, which upregulated the expression of NRF1 to enhance energy metabolism and inhibit skeletal muscle cell apoptosis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0951418X
Volume :
34
Issue :
5
Database :
Complementary Index
Journal :
Phytotherapy Research
Publication Type :
Academic Journal
Accession number :
142949412
Full Text :
https://doi.org/10.1002/ptr.6593