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

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. Highfat 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. K E Y W O R D Sastragaloside IV, energy metabolism, mitochondria, simvastatin, skeletal muscle injury

Astragaloside IV Protects Detrusor from Partial Bladder Outlet Obstruction-Induced Oxidative Stress by Activating Mitophagy through AMPK-ULK1 Pathway

“…What is more, the AS-IV was systemic administrated by gavage in this study; its biofunction on the central nervous system cannot be ignored and should be studied in the future via patch clamp-based methods. Through targeting multiple genes and downstream pathways such as AMPK [29], Hif-1α [30], and TLR4 [31], AS-IV demonstrated potential cardio-protective and immunological enhancement activities through experimentation in vitro and in vivo [32]. In this research, pBOO suppressed the AMPK-Ulk1 signaling, while AS-IV treatment reversed this effect.…”

“…Through targeting multiple genes and downstream pathways such as AMPK [ 29 ], Hif-1 α [ 30 ], and TLR4 [ 31 ], AS-IV demonstrated potential cardio-protective and immunological enhancement activities through experimentation in vitro and in vivo [ 32 ]. In this research, pBOO suppressed the AMPK-Ulk1 signaling, while AS-IV treatment reversed this effect.…”

Research Progress on the Ability of Astragaloside IV to Protect the Brain Against Ischemia-Reperfusion Injury

“…However, most of the data have been obtained in cells, rats and mice, as there have been few clinical trials on the effect of astragaloside IV in stroke patients. We searched for articles on clinical trials of astragaloside IV and found that astragaloside IV has ameliorative effects on skeletal muscle injury ( Jiang et al, 2020 ), precancerous lesions of gastric carcinoma ( Zhang et al, 2018 ), liver fibrosis ( Wang et al, 2021 ), induction of natriuresis ( Ai et al, 2008 ), and heart failure ( Luo et al, 1995 ). However, there are very few clinical publication on the protective effect of astragaloside IV on the brain.…”

Astragaloside IV Promotes the Angiogenic Capacity of Adipose-derived Mesenchymal Stem Cells in a Hindlimb Ischemia Model by FAK Phosphorylation via CXCR2

“…Astragaloside IV, a saponin puri ed from Astragalus, has been widely used for a long time in traditional Chinese medicine to treat ischemic diseases. Numerous studies have shown that Astragalus has positive effects, such as protecting hypoxic myocardial cells [12], promoting angiogenesis [13], inhibiting muscle damage [14]. The potential mechanisms include activation of the PI3K/Akt signaling pathway, JAK2/STAT3 and ERK1/2 signaling pathways [15], AMPK signaling pathway [16] and overexpression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1a (HIF-1a) [17].…”