Modern approach to study the osteoprotective effect of Rhizoma Drynariae

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Modern approach to study the osteoprotective effect of Rhizoma Drynariae

 

Author: Pang, Wai-yin
Title: Modern approach to study the osteoprotective effect of Rhizoma Drynariae
Degree: M.Phil.
Year: 2008
Subject: Hong Kong Polytechnic University -- Dissertations.
Osteoporosis -- Treatment.
Bone regeneration.
Herbs -- Therapeutic use -- China.
Department: Dept. of Applied Biology and Chemical Technology
Pages: xxii, 192 leaves : ill. ; 31 cm.
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b2233755
URI: http://theses.lib.polyu.edu.hk/handle/200/1575
Abstract: Rhizoma Drynariae (RD, Gu Sui Bu) has been one of the most frequently used herbs prescribed for bone fracture healing in China for thousands of years. It is postulated that total flavonoids fraction of Rhizoma Drynariae and its active ingredients benefits the prevention and treatment of osteoporosis. In the present study, the dose response effects of RD total flavonoids extract and its active ingredient, Naringin, on bone metabolism were evaluated using 4-week old ovariectomized (OVX) female C57BL/6J mice orally administered with corresponding agents for 6 weeks. We found that 0.173 mg/g/day RD total flavonoids and 0.4 mg/g/day Naringin significantly restored bone mineral densities (BMD) and bone strengths at mice distal femur, proximal tibia, and lumbar spine from OVX-induced osteopenia without exhibiting uterotrophic side-effect (p<0.05 versus vehicle-treated OVX mice). Decreased levels of urinary calcium and urinary deoxypyridinolines (Dpd) suggested that RD total flavonoids and Naringin might exert bone protective effect via its inhibiting effect on bone resorption (p<0.05 versus vehicle-treated OVX mice). The osteoprotective effects of RD total flavonoids, Naringin and other RD isolated single compounds were also investigated using rat osteoblastic-like UMR-106 cells. RD total flavonoids, Naringin and some RD single compounds significantly stimulated cell proliferation and differentiation in a dose-dependent manner (p<0.05 versus vehicle-treated). The optimal doses of each agent were deduced from the corresponding cell proliferative effects. The involvement of estrogen receptor (ER) in their activities was determined. We found that RD total flavonoids and Naringin modulated osteoclastogenesis by increasing osteoprotegrin (OPG) and decreasing receptor activator of NF-kB ligand (RANKL) mRNA expression simultaneously (p<0.05 versus vehicle-treated). The modulation of osteoclastogenesis by Rhizoma Drynariae and Naringin were abolished by co-treating with estrogen antagonist, ICI 182,780, suggesting that the activation of osteoblastic functions were ER-mediated. From the detection of ER-a / ER-b-mediated estrogen receptor element (ERE)-luciferase activity and the protein expression of phospho-ER-a, RD total flavonoids and Naringin were found to activate ER-a phosphorylation as well as direct ERE binding. The results suggest that RD total flavonoids and Naringin exert stimulatory effects on osteoblastic functions through mechanisms that are similar to those of estrogen or growth factors which promote cell activities. Taken together, Rhizoma Drynariae total flavonoids and Naringin treatment can effectively suppress the OVX-induced uncoupled bone remodeling possibly by both an increase in osteoblastic activities and a decrease in osteoclastogenesis in an ER dependent manner. The present study provides the evidence that Rhizoma Drynariae and its active ingredients can be developed as alternative therapeutic agents for the prevention and treatment of osteoporosis.

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