TY - JOUR
T1 - A Triterpene Glycoside from Black Cohosh that Inhibits Osteoclastogenesis by Modulating RANKL and TNFα Signaling Pathways
AU - Qiu, Samuel X.
AU - Dan, Chun
AU - Ding, Li Sheng
AU - Peng, Shulin
AU - Chen, Shao Nong
AU - Farnsworth, Norman R.
AU - Nolta, Jan
AU - Gross, Michael L.
AU - Zhou, Ping
PY - 2007/7/30
Y1 - 2007/7/30
N2 - 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 TNFα, 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 TNFα. This blockage of osteoclastogenesis elicited by ACCX results from abrogation of the NF-κB and ERK pathways induced by either RANKL or TNFα, respectively. Importantly, this compound attenuates TNFα-induced bone loss in vivo. Therefore, ACCX represents a potential lead for the development of a new class of antiosteoporosis agents.
AB - 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 TNFα, 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 TNFα. This blockage of osteoclastogenesis elicited by ACCX results from abrogation of the NF-κB and ERK pathways induced by either RANKL or TNFα, respectively. Importantly, this compound attenuates TNFα-induced bone loss in vivo. Therefore, ACCX represents a potential lead for the development of a new class of antiosteoporosis agents.
KW - CHEMBIOL
KW - SIGNALING
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U2 - 10.1016/j.chembiol.2007.06.010
DO - 10.1016/j.chembiol.2007.06.010
M3 - Article
C2 - 17656322
AN - SCOPUS:34447566882
VL - 14
SP - 860
EP - 869
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 7
ER -