Triterpenoids from Cimicifugae rhizoma, a novel class of inhibitors on bone resorption and ovariectomy-induced bone loss.
OBJECTIVE
Increasing research suggested that Cimicifugae rhizoma might be protective against osteoporosis. In this study, we investigated the effects of three cycloartane-type triterpenoids isolated from Cimicifugae rhizoma, cimicidol-3-O-beta-D-xyloside (1), cimicidanol-3-O-beta-D-xyloside (2) and acetylacteol-3-O-beta-d-xyloside (3) on bone resorption in vitro and bone loss in ovariectomized (OVX) mice.


METHODS
The activities of the tested compounds on bone resorption were evaluated using three assays, neonatal mouse parietal bone organ culture, osteoclast-like cells (OCLs) formation and pit formation. The effects on bone mineral density (BMD) and uterine weight were examined using OVX mice. Using LC-MS/MS method, the serum concentrations of the triterpenoids were measured in mice serum collected at 0.5, 1, 3, 6 and 12h following its oral administration.


RESULTS
All of the tested compounds exerted the inhibitory effects on bone resorption in bone organ culture, suppressed both of the formation and the resorbing activity of OCLs. Furthermore, a synergistic effect was observed among those compounds. In vivo studies revealed that compounds 1-3 and the mixture of compounds 1-3 prevented the bone loss in OVX mice without affecting uterine weight, and each compound was detected in the mice serum after single oral administration.


CONCLUSIONS
The triterpenoids exerted the inhibitory effects on osteoclastic bone resorption through the suppression of both OCLs formation and the resorbing activity of OCLs, and also showed a significant protective effect on BMD in OVX mice. The present results might provide a new pharmacological potential for the treatment of osteoporosis.
Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China. lijxnju@nju.edu.cn
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Li
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Liu
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He
Z Y
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Yu
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Du
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Kadota
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Seto
D000818:Animals; D015992:Body Mass Index; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology; D031885:Cimicifuga / Q000737:chemistry* / Q000145:classification; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D010052:Ovariectomy / Q000009:adverse effects*; D008517:Phytotherapy / Q000379:methods; D013329:Structure-Activity Relationship; D016896:Treatment Outcome; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification
D004365:Drugs, Chinese Herbal; D014315:Triterpenes