Effect of icariside II and metformin on penile erectile function, glucose metabolism, reaction oxygen species, superoxide dismutase, and mitochondrial autophagy in type 2 diabetic rats with erectile dysfunction

BACKGROUND: Icariside II (ICAII) is a flavonoid isolated from herb Epimedium that has been shown to improve erectile function in rats. However, ICAII’s underlying mechanism remains unclear. METHODS: Type 2 diabetes mellitus erectile dysfunction (T2DMED) rats were induced by single intraperitoneal injection of 25 mg/kg streptozotocin (STZ) and fed a high-fat, high-sugar, and high-calorie diet for 8 weeks. In the control and T2DMED groups, rats were administered with normal saline; in the metformin (MET) group, rats were administered with MET at 0.2 g/kg/day; and in the ICAII + MET group, rats were administered with ICA II at 10 mg/kg/day and MET for 0.2 g/kg/day. The deposition of advanced glycation end products (AGEs), expression of receptor for AGEs (RAGEs), reactive oxygen species (ROS), and superoxide dismutase (SOD) activity, and corpus cavernosum smooth muscle cells (CCSMCs) mitochondrial autophagy were measured. We also evaluated the expression of LC3-II/I, Beclin-1, P70S6K, PI3K, AKT, mTOR, phospho-AKT, phospho-mTOR, and phospho-P70S6K. RESULTS: ICAII and MET can improve erectile function, and decrease the levels of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and AGEs in rats with T2DMED. Furthermore, ICAII and MET can decrease excessive CCSMC mitochondrial autophagy and the level of RAGE and oxidant stress in rats with T2DMED. ICAII and MET may enhance signaling via the PI3K-AKT-mTOR pathway in order to reduce the excessive mitochondrial autophagy of CCSMCs. CONCLUSIONS: ICAII may effectively improve penile erectile function via decreasing excessive CCSMCs mitochondrial autophagy, RAGE, and oxidant stress. Furthermore, ICAII may enhance signaling via the PI3K-AKT-mTOR pathway in order to reduce excessive CCSMC mitochondrial autophagy.