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Benth. (Fructus Evodiae, Wuzhuyu). However, due to its lipophilic chemical structure, low water solubility results in poor bio\u2010availability, which limits its broader application. 3\u2010Amino\u201010\u2010hydroxyl\u2010evodiamine (E2) was a water\u2010soluble derivative of evodiamine with good anti\u2010tumour bioactivity previously developed by our team; however, its anti\u2010osteoporosis activity remains unclear. This study demonstrates that E2 inhibits the maturation of osteoclasts and bone resorption promoted by receptor activator of nuclear factor\u2010\u03baB ligand (RANKL). Mechanistically, E2 reduced RANKL\u2010induced activation of nuclear factor kappa B (NF\u2010\u03baB) as well as mitogen\u2010activated protein kinase (MAPK) pathways, causing the suppression of the expression of genes associated with osteoclasts in vitro. These genes included nuclear factor of activated T cells c1 (NFATc1), tartrate\u2010resistant acid phosphatase (TRAP), cathepsin k (CTSK) and dendritic cell\u2013specific transmembrane protein (DC\u2010STAMP). Treatment with E2 in vitro resulted in the attenuation of p\u2010ERK, p\u2010JNK, p\u2010p38 and NFATc1 levels. Furthermore, ovariectomized (OVX) mice treated with E2 showed a decrease in osteoclast formation as well as preservation of bone mass. This study concludes with evidence that E2 decreases osteoclast maturation and bone resorption through the regulation of multiple signalling pathways, thereby exhibiting an osteoprotective role in OVX mice. Consequently, E2 exhibits significant potential as a prospective drug candidate for treating osteoporosis.<\/jats:p>","DOI":"10.1111\/1440-1681.13926","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T05:08:55Z","timestamp":1730783335000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An evodiamine derivative inhibits osteoclast differentiation and protects against <scp>OVX<\/scp>\u2010induced bone loss in mice"],"prefix":"10.1111","volume":"51","author":[{"given":"Chao","family":"Liu","sequence":"first","affiliation":[{"name":"School of Medicine Shanghai University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaxing","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Medicine Shanghai University  Shanghai 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