Crocetin reduces TNBS-induced experimental colitis in mice by downregulation of NFkB.
OBJECTIVE
Ulcerative colitis (UC) is characterized by oxidative and nitrosative stress, leukocyte infiltration and upregulation of proinflammatory cytokines. In this study, we aim to investigate the effects of crocetin and its protective mechanism on 2,4,6- trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice model.


METHODS
Intestinal lesions (judged by macroscopic and histological score) were associated with neutrophil infiltration (measured as increase in myeloperoxidase (MPO) activity in the mucosa), and high levels of malondialdehyde MDA (an indicator of lipid peroxidation).


RESULTS
Dose-response studies revealed that treatment of mice with crocetin (50 mg/kg/day) i.g. for 8 days) significantly ameliorated diarrhea and the disruption of colonic architecture. Higher and lower doses (100 and 25 mg/kg/day) did not exhibit comparable effects. In crocetin-treated mice, a significant reduction was noted in the degree of both neutrophil infiltration (measured as decrease in myeloperoxidase activity) and lipid peroxidation (measured as decrease in malondialdehyde activity) in the inflamed colon. Crocetin also reduced the levels of nitric oxide (NO) associated with the favorable expression of TH1 and TH2 cytokines and inducible NO synthase along with the down regulation of nuclear factor-kB (NFkB).


CONCLUSIONS
These findings suggest that crocetin exerts beneficial effects in experimental colitis, and therefore we propose that this carotenoid may have therapeutic implications for human UC and can be administered along with the conventional therapy of UC.
Kazi
Hamid A
HA
Department of Pharmacology, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, PR China.
Qian
Zhiyu
Z
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D002338:Carotenoids / Q000008:administration & dosage*; D003092:Colitis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D014801:Vitamin A / Q000031:analogs & derivatives
D000975:Antioxidants; D016328:NF-kappa B; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D014302:Trinitrobenzenesulfonic Acid; D004247:DNA