title: Effects and mechanisms of total glucosides of paeony on adjuvant arthritis in rats.
abstract: Total glucosides of paeony (TGP) is the major active constituent of Paeonia lactiflora Pall. The present study was carried out to investigate the effects of TGP on adjuvant arthritis (AA) of rat and its possible mechanisms. AA was induced by metatarsal footpad injection with complete Freund's adjuvant in male Sprague-Dawley rats. The secondary inflammatory reaction was evaluated by hind paw swelling, polyarthritis index. Activity of interleukin-1 (IL-1) was detected by Con A-induced thymocytes proliferation of C57BL/6J mice assay. The tumor necrosis factor alpha (TNFalpha), prostaglandin E(2) (PGE(2)) and cyclic adenosine monophosphate (cAMP) levels in synoviocytes were assessed by radioimmunoassay (RIA). PGE(2) receptors, EP2 and EP4, were analyzed by Western blot analysis. The level of IL-6 was measured by ELISA. Intragastric administration of TGP (50,100 mg/kg) significantly decreased secondary inflammatory reaction in AA rats. Suppressing the activity of IL-1 and TNFalpha, decreased PGE(2) and increased cAMP levels in synoviocytes of AA rats were observed after administration of TGP. In the immunoblot analysis, TGP could up-regulate the expression of EP2 and EP4. These results showed TGP significantly inhibited the progression of AA, and the inhibitory effects might be associated with its ability to mediate the level of cAMP and inhibit the production of IL-1, TNFalpha, IL-6 and PGE(2) from activated synoviocytes.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology in Anhui Province, Hefei 230032, Anhui Province, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Jia
authors.forename: Yan
authors.initials: Y
authors.lastname: Chang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D029596:Paeonia / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D000242:Cyclic AMP; D015232:Dinoprostone; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors