Effects and mechanisms of total glucosides of paeony on joint damage in rat collagen-induced arthritis.
OBJECTIVE
To investigate the therapeutic effects and mechanisms of total glucosides of paeony (TGP), an effective compound of Chinese traditional herbal medicine (CTM), on collagen -induced arthritis (CIA) in rats.


METHODS
CIA was induced in male Sprague-Dawley rats immunized with chicken type II collagen in Freund's complete adjuvant.


METHODS
TGP (25, 50, 100 mg/kg/d) was orally administered to rats from day 14 to 28 after immunization.


METHODS
Arthritis was evaluated by hind paw swelling, polyarthritis index, and histological examination. Activities of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) were determined and the ultrastructure of synoviocytes was observed. The proliferation and the production of vascular epidermal growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase 1 (MMP-1) and MMP-3 in fibroblast-like synoviocytes (FLS) were detected.


RESULTS
The administration of TGP (25, 50, 100 mg/kg, ig x 14 days) suppressed secondary inflammatory reactions and histological changes in CIA model. The ultrastructure of synoviocytes from CIA rats was changed, and the level of IL-1 and TNF alpha produced by macrophage-like synoviocytes (MLS) from CIA rats was elevated. TGP (50, 100 mg/kg, ig x 14 days) inhibited above changes significantly. The MLS supernatants of CIA rats induced more cell proliferation and more production of VEGF, bFGF, MMP-1 and MMP-3 in FLS of CIA than those supernatants from CIA rats treated with TGP (50, 100 mg/kg, ig x 14 days).


CONCLUSIONS
These results indicate that TGP exerts a suppressive effect on joint destruction in rat CIA. The therapeutic effect of TGP could be associated with its ability to ameliorate the secretion and metabolism of synoviocytes and to inhibit the abnormal proliferation and VEGF, bFGF, MMP-1 and MMP-3 production by FLS.
Zhu
L
L
Institute of Clinical Pharmacology, Anhui Medical University, 230032 Hefei, China.
Wei
W
W
Zheng
Y-Q
YQ
Jia
X-Y
XY
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology*; D015153:Blotting, Western; D049109:Cell Proliferation; D002645:Chickens; D003094:Collagen / Q000378:metabolism*; D004365:Drugs, Chinese Herbal; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005960:Glucosides / Q000737:chemistry* / Q000378:metabolism; D049671:History, 18th Century; D007249:Inflammation; D007375:Interleukin-1 / Q000378:metabolism; D007596:Joints / Q000187:drug effects / Q000473:pathology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D029596:Paeonia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000166:cytology / Q000648:ultrastructure; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D005960:Glucosides; D007375:Interleukin-1; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors; D003094:Collagen; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1