Mollugin attenuates glucocorticoid-induced osteoporosis in rats via Akt/P13K pathway
Purpose: To investigate the protective effect of mollugin on glucocorticoid (GC)-induced osteoporosis in rats.
Methods: A total of 30 female Sprague Dawley rats (weighing 180 to 200 g) were randomly assigned to five groups of six rats each: control, GC and mollugin groups (20, 40 and 80 mg/kg, respectively). Except for the control group, osteoporosis was induced in the rats by intramuscular administration of dexamethasone at a dose of 2.5 mg/kg twice weekly for nine weeks. Bone mineral density (BMD) and serum activities of tartrate-resistant acid phosphatase (TRAP) and specific alkaline phosphatase (ALP), and levels of collagen type I fragment (CTX) and osteocalcin were estimated. The effect of mollugin alone, and in the presence of PI3K/Akt inhibitor on the proliferation of bone marrow osteoblasts was investigated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-tetrazolium bromide (MTT) assay. Western blotting was used for determination of the expressions of p-Akt, Akt and cyclin D1 protein.
Results: There were significant increases in body weights of rats in GC group, when compared with the control group. However, treatment with mollugin significantly reduced the body weights in a dosedependent manner (p < 0.05). The BMD was significantly reduced in GC group, relative to the control group (p < 0.05). Serum activities of TRAP and ALP were significantly higher in GC group than in control group, but were significantly reduced by mollugin treatment (p < 0.05). Serum level of CTX was significantly increased and osteocalcin reduced in the GC group, relative to control (p < 0.05). Osteoblast proliferation was significantly higher in the mollugin-treated groups. The expressions of p-Akt, Akt and cyclin D1 were significantly and dose-dependently higher in mollugin-treated groups (p < 0.05). There were more viable osteoblasts in the mollugin-treated groups than in the untreated group. However, treatment with mollugin in the presence of PI3K/Akt inhibitor significantly reduced their viability (p < 0.05).
Conclusion: Mollugin has therapeutic potential for GC-induced osteoporosis via mechanism involving the PI3K/Akt pathway.
Keywords: Mollugin, Osteoporosis, Bone, PI3K/Akt inhibitor, Osteoblast