Mangiferin attenuates the symptoms of dextran sulfate sodium-induced colitis in mice via NF-κB and MAPK signaling inactivation

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal (GI) tract, and currently no curative treatment is available. Mangiferin, a natural glucosylxanthone mainly from the fruit, leaves and stem bark of a mango tree, has a strong anti-inflammatory activity. We sought to investigate whether mangiferin attenuates inflammation in a mouse model of chemically induced IBD. Pre-administration of mangiferin significantly attenuated dextran sulfate sodium (DSS)-induced body weight loss, diarrhea, colon shortening and histological injury, which correlated with the decline in the activity of myeloperoxidase (MPO) and the level of tumor necrosis factor-alpha (TNF-alpha) in the colon. DSS-induced degradation of inhibitory kappa B alpha (I kappa B alpha) and the phosphorylation of nuclear factor-kappa B (NF-kappa B) p65 as well as the mRNA expression of proinflammatory mediators (inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), TNF-alpha, interleukin-1 beta (IL-1 beta) and IL-6) in the colon were also downregulated by mangiferin treatment. Additionally, the phosphorylation/activation of DSS-induced mitogen-activated protein kinase (MAPK) proteins was also inhibited by mangiferin treatment. In accordance with the in vivo results, mangiferin exposure blocked TNF-alpha-stimulated nuclear translocation of NF-kappa B in RAW264.7 mouse macrophage cells. Transient transfection gene reporter assay performed in TNF-alpha-stimulated HT-29 human colorectal adenocarcinoma cells indicated that mangiferin inhibits NF-kappa B transcriptional activity in a dose-dependent manner. The current study clearly demonstrates a protective role for mangiferin in experimental IBD through NF-kappa B and MAPK signaling inhibition. Since mangiferin is a natural compound with little toxicity, the results may contribute to the effective utilization of mangiferin in the treatment of human IBD. (C) 2014 Elsevier B.V. All rights reserved.