Anti-rheumatoid arthritic effect of madecassoside on type II collagen-induced arthritis in mice.
Madecassoside is the highest amount of triterpene constituent in Centella asiatica herbs, a frequently prescribed crude drug in southeastern Asian and China for wound healing and scar management. The present study aimed to investigate the therapeutic potential and underlying mechanisms of madecassoside on collagen II (CII)-induced arthritis (CIA) in mice. Madecassoside (10, 20 and 40mg/kg), orally administered from the day of the antigen challenge for twenty consecutive days, dose-dependently alleviated the severity of the disease based on the reduced clinical scores, and elevated the body weights of mice. Histopathological examination indicated that madecassoside alleviated infiltration of inflammatory cells and synovial hyperplasia as well as protected joint destruction. Moreover, madecassoside reduced the serum level of anti-CII IgG, suppressed the delayed type hypersensitivity against CII in ears, and moderately suppress CII-stimulated proliferation of lymphocytes from popliteal lymph nodes in CIA mice. In vitro, madecassoside was ineffective in the activation of macrophages caused by lipopolysaccharide. It was concluded that madecassoside substantially prevented mouse CIA, and might be the major active constituent of C. asiatica herbs responsible for clinical uses for rheumatoid arthritis. The underlying mechanisms of action may be mainly through regulating the abnormal humoral and cellular immunity as well as protecting joint destruction.
Liu
Mei
M
Department of Pharmacology of China Materia Medica, China Pharmaceutical University, 1 Shennong Road, Nanjing 210038, China.
Dai
Yue
Y
Yao
Xiujuan
X
Li
Ying
Y
Luo
Yubin
Y
Xia
Yufeng
Y
Gong
Zhunan
Z
D000284:Administration, Oral; D000818:Animals; D000906:Antibodies / Q000097:blood; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D024043:Collagen Type II / Q000494:pharmacology; D007596:Joints / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000096:biosynthesis; D009573:Nitrites / Q000032:analysis*; D014315:Triterpenes / Q000627:therapeutic use*
D000906:Antibodies; D018501:Antirheumatic Agents; D024043:Collagen Type II; D008070:Lipopolysaccharides; D009573:Nitrites; D014315:Triterpenes; D009569:Nitric Oxide; C093443:madecassoside