Antiosteoporotic activities of isoquercitrin in ovariectomized rats: Role of inhibiting hypoxia inducible factor-1 alpha

Abstract

Postmenopausal osteoporosis is a common and disabling disorder that increases the risk of bone fractures due to estrogen deprivation; this can be simulated in rats by ovariectomy. Hypoxia inducible factor-1 alpha (HIF-1α) expression in osteoclasts predominantly leads to its activation increasing bone resorption. Premenopausal, estrogen prevents HIF-1α expression maintaining bone density. Unfortunately postmenopausal estrogen replacement therapy is not recommended due to its potential tumor development risk. Isoquercitrin, a common edible plants phytoestrogen, is known to inhibit HIF-1α. This study was conducted to investigate the potential antiosteoporotic activity of isoquercitrin (15, 30 and 60 mg/kg/day) in ovariectomized rats with reference to 17β-estradiol (25 mcg/kg/day). Animals were bilaterally ovariectomized to induce osteoporosis and one month later they were assigned into groups and administered isoquercitrin and 17β-estradiol for 8 weeks. Ovariectomy reduced lumbar compression strength, distorted bone microscopic architecture, inducing cartilage and trabecular dystrophy, and increased the markers of bone turnover (serum alkaline phosphatase and osteocalcin and urinary calcium, phosphorus and creatinine). It also increased the gene expression of HIF-1α and the levels of nuclear factor-kappa B (NF-κB) and decreased the expression of vascular endothelial growth factor (VEGF) and β-catenin in the femurs. Isoquercitrin was found to improve bone histological features, increase lumbar strength and improve most of the biochemical markers of bone turnover in a manner comparable to 17β-estradiol. Isoquercitrin also attenuated the increased HIF-1α expression while increased that of the VEGF and β-catenin. It also decreased the levels of NF-κB. Therefore isoquercitrin may be considered a safer alternative for managing osteoporosis.