Ginkgetin aglycone exerts anti-osteoporotic effect via regulation of NOX4/Akt/PI3K pathway

Purpose: To investigate the protective effect of Ginkgetin aglycone (GA) on ovariectomy-induced osteoporosis in rats, as well as the mechanism of action involved. Methods: Adult female Wistar rats (n = 40) were separated into four group: normal control, ovariectomy (OVR), 100 mg GA/kg dose, and 200 mg GA/kg dose. The rats were ovariectomized using standard procedures, except for those in normal control group. Rats in the two treatment groups received 100 or 200 mg GA/kg orally for a period of 12 weeks. Biochemical assays were performed on the urine and blood. Markers of bone formation and mediators of inflammation were assessed. Bone microarchitectural changes were examined using micro-CT scanner, while Western blotting was used to determine the expressions of NOX4, NF-κB p65, PI3K, Akt and JNK proteins in rat femurs. Results: Phosphorus and calcium levels in the serum varied among different groups. Levels of calcium, phosphorus and creatinine decreased (p < 0.01) significantly to a greater extent in the urine of GA group than in that of OVR group (p < 0.05). Interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α) and osteocalcin (OC) levels and the activity of alkaline phosphatase (ALP) decreased more in GA group than in OVR group. In GA-treated group, bone mineral density (BMD) was enhanced in a dose dependent manner than OVR group (p < 0.05). Treatment with GA ameliorated altered bone microarchitecture in OVR rats. Treatment of osteoporotic rats with GA led to significant and dosedependent decrease in the expressions of JNK, NOX4, NF-κB p65 and PI3K, and (p < 0.05) increase in the expression of Akt in femur tissue. Conclusion: In conclusion, result of study proves the anti-osteoporotic activity of GA is exerted via regulation of NOX4/PI3K/Akt pathway.