Effects and mechanisms of Paeoniflorin, a bioactive glucoside from paeony root, on adjuvant arthritis in rats.
OBJECTIVE
Paeoniae alba Radix has been recognized as a valuable herb in the treatment of rheumatoid arthritis (RA) in traditional Chinese medicine. The purpose of this study was to investigate the effects of Paeoniflorin (PF), a bioactive glucoside from paeony root, on the rats with adjuvants arthritis (AA) and underlying mechanisms.


METHODS
AA was induced by injecting Complete Freund's adjuvant (10 mg/ml) into hind paw in male Sprague-Dawley rats.


METHODS
PF (5, 10, 20 mg/kg/d) was orally administered to the rats 14 to 20 days after injection of complete Freund's adjuvant.


METHODS
Arthritis was evaluated by hind paw swelling, polyarthritis index, immune organ weights, and histological examination. Interleukin-1 (IL-1) activity was assessed by thymocyte proliferation as quantified by the 3-(4, 5-2dimethylthiazal- 2yl) 2,5-diphenyltetrazoliumbromide (MTT) assay. The content of prostaglandin E2 (PGE2) was measured by radioimmunoassay. The levels of IL-6, granulocyte macrophage colony stimulating factor (GM-CSF) and vascular epidermal growth factor (VEGF) in synovium homogenates were measured by enzyme-linked immuno-absorbent assay (ELISA) respectively. Expression of inhibitory subunits of G protein (G i) and cyclo-oxygenase-2 (COX-2) were detected by Western blotting technique.


RESULTS
There were significant secondary inflammatory reactions in AA rats, which were accompanied by a decrease in immune organ weights. The administration of PF (10, 20 mg/kg/day, i. g., days 14-20) inhibited the inflammatory response and restored the weight of immune organs of AA rats. Synoviocyte proliferation of AA rats increased significantly, and the levels of IL-1, PGE2, IL-6, VEGF and GM-CSF in synovial homogenates of AA rats were also elevated compared with the normal group. The administration of PF (10, 20 mg/kg/day, i.g., days 14-20) reduced the above changes significantly. Finally, the expression of Gi1, Gi2, Gi3 and COX-2 in synovial homogenates of AA rats were also elevated. The administration of PF reduced Gi expression at doses of 10 and 20 mg/kg and decreased COX-2 expression at a dose of 20 mg/kg.


CONCLUSIONS
PF suppresses rat AA at least partly by inhibiting abnormal proliferation of synoviocytes and the production of IL-1, PGE2, IL-6, VEGF and GM-CSF by synoviocytes and reducing Gi and COX-2 expression in synovium.
Zheng
Y-Q
YQ
Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, PR China. yongqiuzheng@sina.com
Wei
W
W
Zhu
L
L
Liu
J-X
JX
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D039821:Monoterpenes; D029596:Paeonia; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D006027:Glycosides
D001565:Benzoates; D001952:Bridged-Ring Compounds; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D005620:Freund's Adjuvant; D019204:GTP-Binding Proteins; D005960:Glucosides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015850:Interleukin-6; D039821:Monoterpenes; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; C015423:peoniflorin; D006027:Glycosides; C489691:Ptgs2 protein, rat