@entity5188 derivative of XXXX inhibits osteoclastic bone resorption and prevents ovariectomy-induced @entity604 .

@entity137 @entity19 @entity604 @entity170 @entity185 @entity5188 @entity21242
OBJECTIVE: Through bioassay-guided natural product research, it has been discovered that @entity21242 and its glycosides possess an antibone resorption activity. @entity5188 derivative of @entity21242 (QOA-8a), a novel compound, is sourced from a structural modification of @entity21242 . The aim of the present study was to evaluate the activities of QOA-8a on bone resorption in vitro and its osteoprotective effect in vivo. METHODS: Osteoclast precursors and mature osteoclasts were used to assay antibone resorption activities in vitro. RAW264.7 cells cultured for 2 days in the presence of the receptor activator for nuclear factor kB ligand were used as osteoclast precursors. Mature osteoclasts were generated from either primary cultures of @entity19 bone marrow-derived macrophages or RAW264.7 cells. Eight-week-old female @entity19 that underwent either ovariectomy or sham surgical operation were used for the evaluation of the osteoprotective effect of QOA-8a at doses of 0.1, 1, and 10 mg kg(-1) day(-1). RESULTS: QOA-8a significantly inhibited the differentiation, formation, and bone resorptive activity of mature osteoclasts without @entity137 . QOA-8a selectively induced apoptosis at an early stage of mature osteoclasts at least via increasing the @entity185 activity, but not osteoclast precursors. Furthermore, QOA-8a significantly prevented @entity604 in ovariectomized @entity19 without any hormone-like adverse effects, whereas the @entity19 treated with 1 mg kg(-1) day(-1) kept the same bone mineral density level as that of the sham @entity19 . CONCLUSIONS: QOA-8a inhibits bone resorption without @entity137 and prevents @entity604 without any hormone-like adverse effects. Although further investigations are necessary to elucidate the detailed molecular mechanisms, QOA-8a demonstrates great potential as a novel agent for the treatment of @entity170 .
