Objective: To investigate the effect of astragaloside on osteoporosis in ovariectomized rats and its mechanism by forkhead box O3a(FoxO3a)/Wnt2/β-catenin signal pathway. Method: Female SD rats were randomly divided into 6 groups:shamed operation group

positive control group (Nilestriol

1.5 mg·kg-1)

model group

low

middle and high-dose astragaloside groups (20

40

80 mg·kg-1) (n=8). The animal model of osteoporosis in postmenopausal rats was replicated through bilateral ovariectomy. After 6 weeks

the drugs were given by gavage once a day for 8 weeks. The serum contents of bone gla protein(BGP)

calcitonin(CT)

osteoprotegerin(OPG)

receptor activator for nuclear factor-κB ligand(RANKL)

malondialdehyde(MDA)

catalase(CAT)

glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD) were detected by enzyme-linked immunosorbent assay(ELISA) kits; bone mineral density(BMD) in lumbar spine and lumbar vertebra was tested by double energy X rays(DEXA)

and bone biomechanical properties were analyzed by three point bending test. The expressions of β-catenin

FoxO3a

Wnt2

p66shc

p-p66shc were measured by Western blot. Result: Compared with the model group

the levels of CT and OPG were significantly decreased

while BGP and RANKL were significantly increased (P<0.05) in the astragaloside groups. astragaloside significantly elevated BMD in lumbar spine and lumbar vertebra (P<0.05)

and the maximum load and maximum stress of tibia (P<0.01).Meanwhile

the content of MDA was significantly decreased (P<0.05)

whereas the levels of CAT

SOD and GSH-PX were increased. Western blot showed that astragalloside significantly reduced p-p66shc/p66shc (P<0.05)

inhibited the expression of FoxO3a (P<0.01) and increased β-catenin and Wnt2 (P<0.05

P<0.01). Conclusion: Astragaloside can effectively relieve osteoporosis induced by oxidative stress in ovariectomized rats

which may be related to the regulation of FoxO3a/Wnt2/β-catenin pathway.