Triterpenoid Saponin W3 from Anemone flaccida Suppresses Osteoclast Differentiation through Inhibiting Activation of MAPKs and NF-κB Pathways.
Excessive bone resorption by osteoclasts within inflamed joints is the most specific hallmark of rheumatoid arthritis. A. flaccida has long been used for the treatment of arthritis in folk medicine of China; however, the active ingredients responsible for the anti-arthritis effects of A. flaccida are still elusive. In this study, W3, a saponin isolated from the extract of A. flaccida was identified as the major active ingredient by using an osteoclast formation model induced by receptor activator of nuclear factor kappa-B ligand (RANKL). W3 dose-dependently suppressed the actin ring formation and lacunar resorption. Mechanistic investigation revealed that W3 inhibited the RANKL-induced TRAF6 expression, decreased phosphorylation of mitogen-activated protein kinases (MAPKs) and IκB-α, and suppressed NF-κB p65 DNA binding activity. Furthermore, W3 almost abrogated the expression of c-Fos and nuclear factor of activated T cells (NFATc1). Therefore, our results suggest that W3 is a potential agent for treating lytic bone diseases although further evaluation in vivo and in clinical trials is needed.
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700 Beijing, China.
Xiangying
X
Kong
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700 Beijing, China.
Yue
Y
Yang
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700 Beijing, China.
Wenbin
W
Wu
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700 Beijing, China.
Hongye
H
Wan
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700 Beijing, China.
Xiaomin
X
Li
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700 Beijing, China.
Michun
M
Zhong
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700 Beijing, China.
Xiaohui
X
Su
2. Guangzhou Kanghe Pharmaceutical Limited Company, 511440 Guangzhou, China.
Shiwei
S
Jia
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700 Beijing, China.
Na
N
Lin
D000199:Actins / Q000378:metabolism; D031883:Anemone / Q000737:chemistry*; D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D053245:RANK Ligand; D000067996:RAW 264.7 Cells; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism
D000199:Actins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D012503:Saponins; D048029:TNF Receptor-Associated Factor 6; C505689:Tnfsf11 protein, mouse
Anemone flaccida; Bone resorption; Osteoclasts; RANKL