Icariin ameliorates osteoporosis by activating autophagy in ovariectomized rats

Background.Osteoporosis (OP) is a major problem that increases the mortality and disability rate worldwide.With an increase in the aging population, OP has become a major public threat to human health.Searching for effective and suitable targets for drug treatment in OP has become an urgent need. Objectives.Osteoporosis is a metabolic bone disease characterized by reduced bone mass and density as well as micro-architectural deterioration.Icariin is a flavonoid extracted from plants of the genus Epimedium and has been shown to exert potential anti-OP activity.The present study was designed to observe the effect of icariin on OP and to clarify the underlying mechanisms in ovariectomized (OVX) rats. Materials and methods.Hematoxylin and eosin (H&E) staining, von Kossa staining and micro-computed tomography (micro-CT) confirmed significant bone loss in the OVX group.Protein expression level was detected with western blot analysis.Results.Icariin reversed a trend of increased bone turnover by reducing serum alkaline phosphatase (ALP), procollagen type I N-terminal propeptide (PINP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and C-telopeptide of type I collagen (CTX-I).Furthermore, icariin decreased sequestosome 1 (p62) and increased microtubule-associated protein 1 light chain 3II/microtubule-associated protein 1 light chain 3I (LC3II/LC3I), autophagy-related protein 7 (Atg7), and Beclin 1 in the femur of OVX rats, improving the indicators of impaired autophagy in OP. Conclusions.Icariin reversed the significant upregulation of the serine/threonine protein kinase (Akt), mammalian target of rapamycin (mTOR) and unc-51-like autophagy activating kinase 1 (ULK1) at Ser757, and the downregulation of p-AMP-activated protein kinase (p-AMPK) and ULK1 phosphorylated at Ser555 in the OVX rats, suggesting that the mechanism of icariin action in OP treatment involves the activation and suppression of the AMPK/ULK1 and AKT/mTOR/ULK1 autophagy pathways, respectively.