Inonotus obliquus upregulates muscle regeneration and augments function through muscle oxidative metabolism

Abstract

Abstract Background Skeletal muscle wasting related to aging or pathological conditions is critically associated with the increased incidence and prevalence of secondary diseases including cardiovascular diseases, metabolic syndromes, and chronic inflammations. Much effort is made to develop agents to enhance muscle metabolism and function. Inonotus obliquus (I. obliquus; IO) is a mushroom popularly called chaga and has been widely employed as a folk medicine for inflammation, cardiovascular diseases, diabetes, and cancer in Eastern Europe and Asia. However, its effect in muscle health has not been explored. ObjectiveHere, we aimed to investigate the beneficial effect of IO extract in muscle regeneration and metabolism. MethodsThe effect of I. obliquus extract was investigated on myogenesis and myotube atrophy models of C2C12 myoblasts and muscle regeneration model of mice. The muscle stem cell proliferation and regeneration post muscle injury were employed to further confirm the effect of I. obliquus. The underlying mechanism of I. obliquus was also investigated by the mitochondrial content and oxidative muscle metabolism as well as the activation of AKT and PGC-1α expression. Results The treatment of IO in C2C12 myoblasts led to increased myogenic differentiation and alleviation of dexamethasone-induced myotube atrophy. Network pharmacological analysis using the identified specific chemical constituents of IO extracts predicted protein kinase B (AKT)-dependent mechanisms to promote myogenesis and muscle regeneration. Consistently, IO treatment resulted in the activation of AKT, which suppressed muscle-specific ubiquitin E3 ligases induced by dexamethasone. IO treatment in mice improved the regeneration of cardiotoxin-injured muscles accompanied by elevated proliferation and differentiation of muscle stem cells. Furthermore, it elevated the mitochondrial content and muscle oxidative metabolism accompanied by the induction of peroxisome proliferator-activated receptor γ coactivator α (PGC-1α). Conclusions Our current data suggest that I. obliquus is a promising natural agent in enhancing muscle regenerative capacity and oxidative metabolism thereby preventing muscle wasting.