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
N1 - Funding Information:
We thank Dr. S.L. Teitelbaum and Dr. F.P. Ross for helpful discussion throughout the conduction of these studies. We are grateful to D. Novack for critically reviewing this manuscript. This study was supported in part by National Institutes of Health grants 2R01 DK6184, from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and P50 AT00155, from the Office of Dietary Supplements (ODS), the National Center for Complementary and Alternative Medicine (NCCAM), and the Office for Research on Women's Health (ORWH), as well as by the National Center for Research Resources Grant 2P41 RR00954. The authors want to thank the financial support from the ASP Starter Award (The American Society of Pharmacognosy, 2006) to S.X.Q.
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
UR - https://www.scopus.com/pages/publications/34447566882
U2 - 10.1016/j.chembiol.2007.06.010
DO - 10.1016/j.chembiol.2007.06.010
M3 - Article
C2 - 17656322
AN - SCOPUS:34447566882
SN - 1074-5521
VL - 14
SP - 860
EP - 869
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 7
ER -