alpha-Mangostin ameliorates dextran sulfate sodium -induced colitis through inhibition of NF-kappa B and MAPK pathways

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the colon as a target site. Previous reports regarding the efficacy of alpha-mangostin (alpha MG) to inhibit nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinases (MAPKs) as well as relatively high distribution to the colon suggested the therapeutic potential of this compound in UC model. In dextran sodium sulfate (DSS)-induced colitis mice (DSS mice), the disease activity index scores involving diarrhea, bloody stool, body weight reduction, and myeloperoxidase (MPO) activities of the esophagus and colon increased with the reduced colon length. Also histologic disturbances and changes of NF-kappa B and MAPK pathways including phosphorylation of I kappa B kinase, ERK1/2, SAPK/JNK and p38 were observed in the colon of the DSS mice. However, all of these impaired conditions in the DSS mice were restored by aMG treatment, and the intestinal metabolism of aMG decreased, increasing its distribution to the colons in the DSS mice compared with the control mice. All of these results suggest that high distribution of aMG in the colon might attenuate DSS-induced colitis by inhibiting NF-kappa B and MAPK pathways in the colon.