The Study Of Antiosteoporotic Activity Of Sambucus Williamsii Hance In Vivo And In Vitro

This thesis focus on the effect of Herbal Sambucus williamsii Hance (SWH), which is a folk medical plante with a long history of safe use for treatment of bone fractures and joint diseases in China. In this thesis, we systematically evaluated the in vivo effect of SWH extract on bone metabolism using ovariectomized rat model. Ovariectomized (OVX) or sham-operated (Sham) three months old female Sprague Dawley rats were orally administered with SWH extract (300 or 600 mg/kg/d) , 17β-estrogen (E2, 2 mg/kg/d) or its vehicle for 3 months. SWH extracts did not alter weight gain and uterus weight in OVX rats. SWH extracts significantly increased serum Ca levels (p<0.05, vs. OVX control group) as well as decreased urinary Ca excretion (p < 0.01, vs. OVX control group) in OVX rats. The upregulation of serum alkaline phosphatase, serum osteocalcin as well as urinary deoxypyridinoline levels by OVX was suppressed by treatment with SWH extracts in rats (p < 0.05, vs. OVX control group). SWH extract increased the stiffness of femur at both dosage (p<0.05, vs. OVX control group) and increased tibial bone mineral density at 600 mg/kg body weight/day (p<0.05, vs. OVX control group) in OVX rats. Quantitative computed tomography as well as histomorphometric analysis indicated that SWH extract of both doses as well as E2 treatment could prevent OVX-induced bone loss by increasing tibial trabecular bone mass and bone area in OVX rats (p< 0.05, vs vehicle-treated OVX group). RT-PCR and western blotting analysis showed that type I collagen mRNA as well as protein level increased in proximal femur of OVX rats administrated with SWH extract at the dose of 600 mg/kg/d. And SWH treatment did not alter ERa mRNA expression level in the uterus of OVX rats. Our results indicate that orally administrated SWH extracts can decrease urinary calcium excretion and bone turnover rate in OVX rats, resulting in positive effects on biomechanical strength of bone and bone mineral density. This study is the first to report that SWH could be considered as a potential candidate for management of postmenopausal osteoporosis. Then in vitro experiments were performed to determine the potential molecular mechanism of the anti-osteoporotic effect of SWH. Results suggested that chloroform fraction and ethyl acetate fraction of SWH can inhibit osteoclastogenesis osteoclast by modulating the expression of osteoprotegrin (OPG) and receptor activator of NF-κB ligand...