Amelioration of experimental colitis by Astragalus membranaceus through anti-oxidation and inhibition of adhesion molecule synthesis.
OBJECTIVE
To investigate the protective effects of Astragalus membranaceus (Am) against hapten-induced colitis in male Sprague-Dawley rats as well as its underlying mechanism.


METHODS
Experimental colitis was induced in rats by enema administration of 2,4-dinitrobenzene sulfonic acid (DNBS). Rats were either pretreated with Am extract (2 or 4 g/kg, p.o. once daily) starting from 10 d before DNBS enema, or received Am post-treatment (2 or 4 g/kg, p.o. twice daily) on the three consecutive days following DNBS administration. Colonic lesion area and histological damage were determined, while the activities of myeloperoxidase (MPO) and xanthine oxidase, as well as reduced glutathione (GSH) content were measured in the excised colonic tissues. Besides, protein expression of inducible nitrite oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and P-selectin was also detected by Western blot analysis.


RESULTS
Our findings had shown that both macroscopic lesion area and histological colonic damage induced by DNBS were significantly reduced by both Am pre- and post-treatments. These were accompanied by attenuation of the elevated colonic MPO activity and downregulation of the iNOS, P-selectin, and ICAM-1 protein expression. Besides, deprivation of colonic GSH level under colitis condition was also preserved.


CONCLUSIONS
These results demonstrate that Am possesses both preventive and therapeutic potential in experimental colitis. The anti-inflammatory actions involve anti-oxidation along with inhibition of adhesion molecule synthesis in the colonic tissues.
Ko
Joshua-Ka-Shun
JK
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. jksko@hkbu.edu.hk
Lam
Flora-Ying-Lee
FY
Cheung
Andrew-Pok-Lap
AP
D000818:Animals; D027885:Astragalus propinquus / Q000737:chemistry*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D008516:Medicine, Chinese Traditional; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010084:Oxidation-Reduction; D019007:P-Selectin / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014969:Xanthine Oxidase / Q000378:metabolism
D019007:P-Selectin; D010936:Plant Extracts; D018799:Intercellular Adhesion Molecule-1; C045305:2,4-dinitrofluorobenzene sulfonic acid; D004139:Dinitrofluorobenzene; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D014969:Xanthine Oxidase; D005978:Glutathione