title: A triterpene glycoside from black cohosh that inhibits osteoclastogenesis by modulating RANKL and TNFalpha signaling pathways.
abstract: Osteoporosis is a major age-related source of morbidity and mortality. Increased bone resorption mediated by osteoclasts is central to its pathogenesis. Cytokines, particularly RANKL and TNFalpha, are often increased under pathologic conditions, leading to enhanced osteoclastogenesis. Black cohosh (Actaea/Cimicifuga racemosa L), a popular herbal supplement for the treatment of menopausal symptoms, was recently shown to have the beneficial effect of preventing bone loss. Here, we demonstrate that 25-acetylcimigenol xylopyranoside (ACCX), a triterpenoid glycoside isolated from black cohosh, potently blocks in vitro osteoclastogenesis induced by either RANKL or TNFalpha. This blockage of osteoclastogenesis elicited by ACCX results from abrogation of the NF-kappaB and ERK pathways induced by either RANKL or TNFalpha, respectively. Importantly, this compound attenuates TNFalpha-induced bone loss in vivo. Therefore, ACCX represents a potential lead for the development of a new class of antiosteoporosis agents.
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA.
authors.forename: Samuel X
authors.initials: SX
authors.lastname: Qiu
authors.forename: Chun
authors.initials: C
authors.lastname: Dan
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Ding
authors.forename: Shulin
authors.initials: S
authors.lastname: Peng
authors.forename: Shao-Nong
authors.initials: SN
authors.lastname: Chen
authors.forename: Norman R
authors.initials: NR
authors.lastname: Farnsworth
authors.forename: Jan
authors.initials: J
authors.lastname: Nolta
authors.forename: Michael L
authors.initials: ML
authors.lastname: Gross
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002455:Cell Division; D031885:Cimicifuga / Q000737:chemistry*; D006027:Glycosides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C506863:25-O-acetylcimigenol-3-O-beta-D-xylopyranoside; D006027:Glycosides; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha