Involvement of PI3K/Akt/β-catenin signaling in schisandrin B-mitigated bone deterioration in an experimental rat model of estrogen deficiency

INTRODUCTION: Schisandrin B (SchB) has been reported to perform a wide range of biological functions, including antioxidant activity, anti-inflammatory activity and stimulation of osteoblast proliferation. However, the function and mechanism of SchB in ovariectomy (OVX)-induced osteoporosis are still unknown. The present study was designed to investigate the anti-osteoporotic activity of SchB in an experimental rat model of estrogen deficiency, which is usually used to mimic human postmenopausal osteoporosis (PMO). MATERIAL AND METHODS: OVX rats were orally treated with low (10 mg/kg) or high (50 mg/kg) doses of SchB for 8 weeks. Bone metabolism-related markers were measured by ELISA. The levels of protein expression were determined by western blotting analysis. Hematoxylin and eosin (H&E) and safranin O staining were performed to analyze trabecular bone and cartilage degeneration. Tartrate-resistant acid phosphatase (TRAP) staining was used to evaluate osteoclast differentiation. RESULTS: SchB administration markedly increased serum Ca levels and bone Ca content and decreased urinary calcium excretion in OVX-operated rats. In addition, high-dosage SchB treatment blocked osteoclastogenesis and improved trabecular bone and cartilage degeneration in the tibia of OVX-operated rats. Furthermore, high-dosage SchB treatment dramatically elevated the protein expression of phospho-PI3K, phospho-Akt and β-catenin in OVX-operated rats. CONCLUSIONS: SchB exerted anti-osteoporotic activity in OVX-operated rats by accelerating the phosphorylation of PI3K and Akt, subsequently upregulating the expression of β-catenin.