Curcumin attenuates inflammation through inhibition of TLR-4 receptor in experimental colitis.
Curcumin, an active ingredient of Curcumin longa mediates its anti-inflammatory effects through inhibition of NFkB. Several pathways including toll-like receptors (TLR) induce NFkB leading to inflammation. In this study, we investigated the effects of curcumin on the expression of TLR-4 and MyD88, the upstream signaling pathway in experimental colitis induced in the Sprague-Dawley male rats by intra-rectal administration of trinitrobenzenesulfonic acid (TNBS). The animals which received TNBS were divided into two groups: Group 1, received aqueous suspension of curcumin (100 mg/Kg body weight) 2 h prior to inducing colitis, and the treatment was repeated every day for 5 days, and Group 2 and non-colitis (Group 3) animals received phosphate buffered saline (PBS) in a similar fashion. Non-colitis animals (Group 4) received curcumin and served as controls. Animals were sacrificed on day 5 post-TNBS by cervical dislocation, colon was taken out, and cleaned with PBS. Levels of TLR-4, MyD88, and NFkB proteins were measured using ECL Western blot analysis, and TLR-4 mRNA by a competitive RT-PCR method. Colitis was confirmed histologically by measuring myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels in the colonic tissues. TNBS-induced increase in the level of MPO activity and MDA concentrations was reversed by curcumin treatment, whereas the same dose of curcumin did not affect their levels in the non-colitis animals. Increases in the levels of TLR-4, MyD88, and NFkB proteins in inflamed tissue were also suppressed significantly by curcumin treatment. The level of TLR-4 mRNA remained unchanged in the colitis animals. These findings demonstrate that signaling pathway of curcumin-induced inhibition of inflammation involves TLR-4 and MyD88, and therefore may serve as an important therapeutic target in IBD.
Lubbad
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Department of Biochemistry, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat, Kuwait.
Oriowo
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MA
Khan
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D003092:Colitis / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D009195:Peroxidase; D003474:Curcumin