Icariin promotes skeletal muscle mitochondrial biogenesis by the AMPK-PPARδ-PGC-1α α signaling pathway: A potential mechanism for beneficial muscle function homeostasis

Mitochondrial biogenesis is a key factor in regulating skeletal muscle function and homeostasis. At present, a growing number of natural polyphenols, flavonoids and other compounds have been reported to have the function of regulating skeletal muscle oxidative metabolism. Here, we aimed to explore the effect of the flavonoid compound icariin purified from Epimedium koreanum Nakai in regulating mitochondrial biogenesis in mice and C2C12 myotubes. We found that icariin elevated the inverted suspension time by 1.72-fold and the distance run on the treadmill by 1.52-fold in mice. Daytime respiratory exchange ratio was significantly lower in mice after 8 weeks of icariin treatment compared to control groups. Icariin activated the mitochondrial biogenetic signaling pathway and mitochondrial marker expression, and the mitochondrial size of gastrocnemius and soleus was increased by 2.3-fold and 2.0-fold in mice, respectively. In addition, icariin elevated mitochondrial DNA copy number by 1.41-fold and 1.54-fold in gastrocnemius and C2C12 myotube cells, respectively. In vitro studies showed that inhibition of p-AMPK and PPAR delta could attenuate ICA-regulated mitochondrial biogenetic pathway. Our study suggests that icariin promotes mitochondrial biogenesis and exercise endurance through AMPKPPAR delta-PGC-1 alpha signaling pathway in C57BL/6 J mice skeletal muscle, indicating that icariin may be able to regulate muscle mitochondria function as an exercise mimetic.