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Curcumin is a phenolic natural product isolated from the rhizome of Curcuma longa (turmeric). We evaluated the effects of curcumin on the development of dextran sulfate sodium (DSS)-induced experimental colitis. BALB/c mice were fed a chow containing either 3.5% (wt/wt) DSS or 3.5% DSS + 2.0% (wt/wt) curcumin. The body weight loss was more apparent in DSS-treated mice than in DSS + curcumin-treated mice. The disease activity index, histological colitis score, and MPO activity were all significantly higher in DSS-treated mice than in DSS plus curcumin-treated mice. Microscopically, mucosal edema, cellular infiltration, and epithelial disruption were much more severe in DSS-treated mice than in DSS + curcumin-treated mice. In DSS + curcumin-treated mice, NF-kappaB activation was blocked in the mucosa. In conclusion, the development of DSS-induced colitis was significantly attenuated by curcumin. Being a nontoxic natural dietary product, curcumin could be useful in treatment of IBD patients.

IntroductionImatinib mesylate (Gleevec; imatinib [Glivec]; formerly STI571), a specific inhibitor of ABL tyrosine kinase, is efficacious in treating Philadelphia chromosome-positive (Ph ϩ ) leukemias such as chronic myeloid leukemia (CML) and Ph ϩ acute lymphoblastic leukemia (ALL). 1,2 Within a few years of its introduction to the clinic, imatinib mesylate had dramatically altered the first-line therapy for CML, because it was found that most patients with newly diagnosed CML in the chronic phase (CP) achieved durable responses when treated with imatinib mesylate. 3 However, a small percentage of these patients, as well as most patients with advanced-phase CML and Ph ϩ ALL, relapse on imatinib mesylate therapy. 2,4 Several mechanisms of refractoriness and relapse have been reported, including point mutations within the ABL kinase domain, amplification of the bcr-abl gene, overexpression of bcr-abl mRNA, [5][6][7][8] increased drug efflux via a process mediated by P-glycoprotein (P-gp), 9 and activation of the Src-family protein Lyn. [10][11][12] There has recently been an increase in the numbers of reported cases of isolated central nervous system (CNS) relapse in which mainly patients with CML-blast crisis (BC) and Ph ϩ ALL who continued to have complete cytogenetic responses (CCgR) developed an extramedullary BC in the CNS. [13][14][15][16][17][18][19][20][21][22] Leis et al 23 reported that isolated CNS relapse occurred in 5 (20.8%) of 24 patients whose protocols included imatinib mesylate treatment, whereas Pfeifer et al 24 reported that CNS leukemia developed in 13 (12.1%) of 107 patients with Ph ϩ ALL. Isolated CNS relapse may be due to a limited penetration of imatinib mesylate into the cerebrospinal fluid (CSF), because it has been shown that concentrations of imatinib mesylate in the CSF are 1 to 2 orders of magnitude lower than the corresponding plasma levels. [24][25][26][27] Brain endothelial cells are characterized by their barrier properties, including tight junctions and various selective transporters. One of the transporters in the BBB, P-gp, which is expressed at the luminal side of the endothelial cells of the capillaries in the brain, plays an important role in drug efflux from the brain. Preclinical in vitro and in vivo studies have shown that imatinib mesylate is a substrate for P-gp, so that P-gp limits the distribution of imatinib mesylate to the brain. 28,29 The CNS can thereby become a sanctuary site of relapse in patients who are on prolonged imatinib mesylate therapy.To overcome resistance to imatinib mesylate, we recently developed a specific dual BCR-ABL/Lyn inhibitor, , which is 25 to 55 times more potent than imatinib mesylate in vitro and at least 10 times more potent than The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. Materials and methods Reagents ...

To evaluate the therapeutic effects of the new synthetic sphingosine-1-phosphate (S1P) receptor modulator, FTY720, we investigated how FTY720 affects the development of dextran sulfate sodium (DSS)-induced colitis and CD4 + CD62L + T cell transfer colitis. BALB/c mice were fed a chow containing 3.5% (wt/wt) DSS to induce colitis. The CD4 + CD62L + T cell transfer colitis was induced by an intraperitoneal injection of CD4 + CD62L + spleen T cells into recipient CB17 SCID mice. The FTY720 was administered by lavage at a dose of 0.3 mg/kg/day. FTY720 was effective in preventing the body weight loss in the DSS-colitis model and the CD4 + CD62L + T cell transfer model. The disease activity index, histological colitis score, and MPO activity were all significantly lower in FTY720-treated mice than in the nontreated mice. Microscopically, mucosal edema, cellular infiltration and epithelial disruption were much more moderate in the FTY720-treated mice than in the non-treated mice. In both colitis models, FTY720 prevented the infiltration of CD4 + T cells into the inflamed colonic lamina propria. In conclusion, the development of DSS-colitis and CD4 + CD62L + T cell transfer colitis were significantly attenuated by FTY720. Since FTY720 is an immunosuppressive product that does not modulate T cell functions, it could be useful in the treatment of IBD patients.