title: Mangiferin attenuates the symptoms of dextran sulfate sodium-induced colitis in mice via NF-κB and MAPK signaling inactivation.
abstract: 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-α (TNF-α) in the colon. DSS-induced degradation of inhibitory κBα (IκBα) and the phosphorylation of nuclear factor-kappa B (NF-κB) p65 as well as the mRNA expression of pro-inflammatory mediators (inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), TNF-α, interleukin-1β (IL-1β) 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-α-stimulated nuclear translocation of NF-κB in RAW264.7 mouse macrophage cells. Transient transfection gene reporter assay performed in TNF-α-stimulated HT-29 human colorectal adenocarcinoma cells indicated that mangiferin inhibits NF-κB transcriptional activity in a dose-dependent manner. The current study clearly demonstrates a protective role for mangiferin in experimental IBD through NF-κB 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.
authors.affiliation: Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dou
authors.affiliation: Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Gaiyan
authors.initials: G
authors.lastname: Ren
authors.affiliation: Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ding
authors.affiliation: Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Aning
authors.initials: A
authors.lastname: Sun
authors.affiliation: Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.affiliation: Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wu
authors.affiliation: Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, NY 10461, USA.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Mani
authors.affiliation: Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: wangzht@hotmail.com.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005638:Fruit; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy*; D031022:Mangifera / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy / Q000379:methods*; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D044004:Xanthones / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D044004:Xanthones; C013592:mangiferin; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Dextran sulfate sodium; Inflammatory bowel disease; MAPK; Mangiferin; NF-κB