Madecassoside attenuates inflammatory response on collagen-induced arthritis in DBA/1 mice.
Madecassoside (MA), a triterpenoid product isolated from Centella asiatica, has been described to exhibit antioxidant and anti-inflammatory activities. The present study was undertaken to determine whether madecassoside (MA) is efficacious against collagen-induced arthritis (CIA) in mice and its possible mechanisms. DBA/1J mice were immunized with bovine type II collagen and treated with MA (3, 10 and 30 mg/kg d, i.g.) from days 21 to 42 after immunization. Arthritis was evaluated by hind paw swelling, polyarthritis index, and histological examination. In vitro proliferation of spleen cells was examined using 3-[4,5-dimethylthylthiazol-2-yl]-2, 5-diphenyltetrazoliumbromide (MTT) assay. Plasma levels of cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10) and the expression of prostaglandin E(2) (PGE(2)), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in synovial tissues were also determined. The results showed that comparing with untreated CIA mice, treated with MA dose-dependently suppressed the clinical arthritis score and joints tissues pathological damage, reduced the proliferation of spleen cells, plasma levels of TNF-alpha and IL-6, synovial tissues PGE(2) production and COX-2 protein expression, however, the expression of COX-1 in synovial tissues did not change and the plasma levels of IL-10 were increased. These results suggest that MA can effectively alleviate inflammatory response on CIA, and anti-inflammatory effects of MA can be attributed, at least partially, to the inhibition of pro-inflammatory mediators, including COX-2 expression, PGE(2) production, TNF-alpha and IL-6 levels and the up-regulation anti-inflammatory molecule IL-10.
Li
Hongzhong
H
Department of Pharmacology, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Gong
Xia
X
Zhang
Li
L
Zhang
Zhuo
Z
Luo
Fuling
F
Zhou
Qixin
Q
Chen
Jin
J
Wan
Jingyuan
J
D000818:Animals; D001169:Arthritis, Experimental / Q000517:prevention & control*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D015232:Dinoprostone / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013583:Synovial Membrane / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
D016207:Cytokines; D018836:Inflammation Mediators; D014315:Triterpenes; C093443:madecassoside; D015232:Dinoprostone