title: Total saponin from Anemone flaccida Fr. Schmidt abrogates osteoclast differentiation and bone resorption via the inhibition of RANKL-induced NF-κB, JNK and p38 MAPKs activation.
abstract: Osteoclasts, bone-specialized multinucleated cells, are responsible for bone destructive diseases such as rheumatoid arthritis and osteoporosis. Natural plant-derived products have received substantial attention given their potential therapeutic and preventive activities against bone destructive diseases. In the present study, we investigated the effects of total saponin (TS) from Anemone flaccida Fr. Schmidt, on receptor activator of nuclear factor-κB ligand (RANKL)-induced in vitro osteoclast differentiation. We observed that TS concentration-dependently inhibited RANKL-induced osteoclast formation from RAW 264.7 cell and bone marrow-derived macrophages (BMMs), as well as decreased extent of actin ring formation and lacunar resorption. The RANKL-stimulated expression of osteoclast-related transcription factors were also diminished by TS. Moreover, TS blocked the RANKL-triggered TRAF6 expression, phosphorylation of mitogen-activated protein kinases (MAPKs) and IκB-α, and inhibited NF-κB p65 DNA binding activity. Furthermore, TS almost abrogated the nuclear factor of activated T cells (NFATc1) and c-Fos expression. Taken together, our results demonstrated that TS suppresses RANKL-induced osteoclast differentiation and inflammatory bone loss via the down-regulation of TRAF6 level, suppression of JNK and p38 MAPKs and NF-κB activation, and subsequent decreased expression of c-Fos and NFATc1. Therefore, TS may be a potential agent and needs to be more evaluated in vivo or in clinical trials to become a therapeutic for lytic bone diseases.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing, 100700, China. kongu0051@163.com.
authors.forename: Xiangying
authors.initials: X
authors.lastname: Kong
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing, 100700, China. wenbinwu1985@yahoo.cn.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing, 100700, China. yangyue8675658@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing, 100700, China. redleaf2011@163.com.
authors.forename: Hongye
authors.initials: H
authors.lastname: Wan
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing, 100700, China. lixiaomin89@126.com.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing, 100700, China. zhongmichun@126.com.
authors.forename: Michun
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing, 100700, China. zhaohongyan1997@163.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing, 100700, China. sxh66159@163.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Su
authors.affiliation: Guangzhou Kanghe Pharmaceutical Limited Company, Guangzhou, 511440, China. jiashiwei@263.net.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Jia
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing, 100700, China. judahong@163.com.
authors.forename: Dahong
authors.initials: D
authors.lastname: Ju
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing, 100700, China. linna888@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Lin
mesh_terms: D000199:Actins / Q000378:metabolism; D031883:Anemone / Q000737:chemistry*; D000818:Animals; D001862:Bone Resorption / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D012503:Saponins; D048029:TNF Receptor-Associated Factor 6; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases