Hongliang Wu1,2,
Min Dai3 ,
Minghua Dai2,
Weijie Huang2
1Medical Department of Graduate School, Nanchang University, Nanchang 330031;
2Department of Orthopedics, Shanghai Punan Hospital of Pudong New District, Shanghai 200125;
3Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
For correspondence:- Min Dai
Email: MildrednEvansdl@yahoo.com Tel:+8613767181616
Accepted: 26 August 2019
Published: 30 September 2019
Citation:
Wu H, Dai M, Dai M, Huang W.
Ginkgetin aglycone exerts anti-osteoporotic effect via regulation of NOX4/Akt/PI3K pathway. Trop J Pharm Res 2019; 18(9):1817-1822
doi:
10.4314/tjpr.v18i9.5
© 2019 The authors.
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Abstract
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 micro-architectural 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 dose-dependent 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.
Keywords: Osteoporosis, Osteocalcin, Ginkgetin aglycone, Ovariectomy, Bone mineral density, Cytokines