title: Total glucosides of paeony inhibit the proliferation of fibroblast-like synoviocytes through the regulation of G proteins in rats with collagen-induced arthritis.
abstract: The aim of this study was to investigate the expression of G proteins in fibroblast-like synoviocytes (FLSs) from rats with collagen-induced arthritis (CIA) and to determine the effect of total glucosides of paeony (TGP). CIA rats were induced with chicken type II collagen (CCII) in Freund's complete adjuvant. The rats with experimental arthritis were randomly separated into five groups and then treated with TGP (25, 50, and 100mg/kg) from days 14 to 35 after immunization. The secondary inflammatory reactions were evaluated through the polyarthritis index and histopathological changes. The level of cyclic adenosine monophosphate (cAMP) was measured by radioimmunoassay. The FLS proliferation response was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The toxin-catalyzed ADP-ribosylation of G proteins was performed through autoradiography. The results show that TGP (25, 50, and 100mg/kg) significantly decreased the arthritis scores of CIA rats and improved the histopathological changes. TGP inhibited the proliferation of FLSs and increased the level of cAMP. Moreover, the FLS proliferation and the level of Gαi expression were significantly increased, but the level of Gαs expression was decreased after stimulation with IL-1β (10ng/ml) in vitro. TGP (12.5 and 62.5μg/ml) significantly inhibited the FLS proliferation and regulated the balance between Gαi and Gαs. These results demonstrate that TGP may exert its anti-inflammatory effects through the suppression of FLS proliferation, which may be associated with its ability to regulate the balance of G proteins. Thus, TGP may have potential as a therapeutic agent for the treatment of rheumatoid arthritis.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of the Education Ministry of China, Hefei 230032, China; School of Pharmacy, Anhui Xinhua University, Hefei 230088, China. Electronic address: jiaxiaoyi78@126.com.
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Jia
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of the Education Ministry of China, Hefei 230032, China. Electronic address: changyan318@sohu.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of the Education Ministry of China, Hefei 230032, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Sun
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of the Education Ministry of China, Hefei 230032, China. Electronic address: wuhuaxun01@yahoo.cn.
authors.forename: Hua-Xun
authors.initials: HX
authors.lastname: Wu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of the Education Ministry of China, Hefei 230032, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of the Education Ministry of China, Hefei 230032, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Xu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of the Education Ministry of China, Hefei 230032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of the Education Ministry of China, Hefei 230032, China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of the Education Ministry of China, Hefei 230032, China.
authors.forename: Yong-Qiu
authors.initials: YQ
authors.lastname: Zheng
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of the Education Ministry of China, Hefei 230032, China. Electronic address: Songlh@ankebio.com.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Song
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of the Education Ministry of China, Hefei 230032, China. Electronic address: wwei@ahmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D024043:Collagen Type II / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D029596:Paeonia; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000473:pathology*
chemical_list: D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D005960:Glucosides; D010936:Plant Extracts; D000242:Cyclic AMP; D019204:GTP-Binding Proteins
keywords: Fibroblast-like synoviocytes; G protein; IL-1β; Proliferation; Total glucosides of paeony