title: Total Saponin from Anemone flaccida Fr. Schmidt Prevents Bone Destruction in Experimental Rheumatoid Arthritis via Inhibiting Osteoclastogenesis.
abstract: Anemone flaccida Fr. Schmidt is used in the clinical compound prescription for the treatment of rheumatoid arthritis (RA) in China and has the traditional use of draining dampness, diminishing swelling, and relieving pain. Total saponins (TS) are the characteristic components and also the main active ingredients of A. flaccida. Previous reports indicated that TS possess anti-inflammatory and immunoregulatory properties; however, the effects of TS on bone destruction of RA have not been evaluated. In this study, our data first showed the therapeutic effects of TS on severity of arthritis and arthritis progression in collagen-induced arthritis (CIA) rats. Then, by microfocal computed tomography (CT) quantification, TS significantly increased bone mineral density, bone volume fraction, and trabecular thickness and decreased trabecular separation of inflamed joints both at peri-articular and extra-articular locations. TS also diminished the level of the bone resorption marker CTX-I and simultaneously increased the bone formation marker osteocalcin in sera of CIA rats. Interestingly, TS prevented bone destruction by reducing the number of osteoclasts in inflamed joints, reducing the expression of receptor activator of nuclear factor-κF (RANK) ligand (RANKL) and RANK, increasing the expression of osteoprotegerin (OPG), at both mRNA and protein levels, and decreasing the ratio of RANKL to OPG in inflamed joints and sera of CIA rats. This was further confirmed in the co-culture system of human fibroblast-like synovial and peripheral blood mononuclear cells. In addition, TS inhibited the levels of pro-inflammatory cytokines implicated in bone resorption, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNFα), IL-6, IL-17, and IL-23 in sera and joints. These findings offer convincing evidence that TS attenuate RA partially by preventing both focal bone destruction and systemic bone loss. This anti-erosive effect results in part from inhibiting osteoclastogenesis by regulating the RANKL/RANK/OPG signaling pathway. The suppression of systemic and local pro-osteoclastogenic cytokines by TS was also highly effective.
authors.affiliation: 1 Institute of Chinese Materia Medica , China Academy of Chinese Medical Sciences, Beijing, China .
authors.forename: Chunfang
authors.initials: C
authors.lastname: Liu
authors.affiliation: 1 Institute of Chinese Materia Medica , China Academy of Chinese Medical Sciences, Beijing, China .
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 1 Institute of Chinese Materia Medica , China Academy of Chinese Medical Sciences, Beijing, China .
authors.forename: Danni
authors.initials: D
authors.lastname: Sun
authors.affiliation: 1 Institute of Chinese Materia Medica , China Academy of Chinese Medical Sciences, Beijing, China .
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1 Institute of Chinese Materia Medica , China Academy of Chinese Medical Sciences, Beijing, China .
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: 2 Guangzhou Kanghe Pharmaceutical Limited Company , Guangzhou, China .
authors.forename: Shiwei
authors.initials: S
authors.lastname: Jia
authors.affiliation: 1 Institute of Chinese Materia Medica , China Academy of Chinese Medical Sciences, Beijing, China .|3 State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology , Macau, China .
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: 1 Institute of Chinese Materia Medica , China Academy of Chinese Medical Sciences, Beijing, China .
authors.forename: Na
authors.initials: N
authors.lastname: Lin
mesh_terms: D031883:Anemone / Q000737:chemistry*; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D001862:Bone Resorption / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007596:Joints / Q000187:drug effects / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology*; D010012:Osteogenesis / Q000187:drug effects*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053244:Osteoprotegerin; D053245:RANK Ligand; D012503:Saponins