title: Mangiferin ameliorates colitis by inhibiting IRAK1 phosphorylation in NF-κB and MAPK pathways.
abstract: Mangiferin, a main constituent of the root of Anemarrhena asphodeloides and the leaves of Mangifera indica, inhibits NF-κB activation in macrophages. Therefore, we investigated effect of mangiferin on 2,3,4-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice and its anti-inflammatory mechanism in lipolysaccharide (LPS)- or peptidoglycan-stimulated mouse peritoneal macrophages. Mangiferin inhibited phosphorylation of nuclear factor-kappaB (NF-κB), interleukin-1 receptor-associated kinase 1 (IRAK1), and mitogen-activated protein kinases (MAPK) in peptidoglycan- or LPS-stimulated peritoneal macrophages. Mangiferin in the presence of SN50 inhibited LPS-stimulated NF-κB activation more potently than mangiferin alone. Mangiferin inhibited interaction of fluorescent p-IRAK1 antibody to LPS-stimulated peritoneal macrophages, but increased binding of fluorescent IRAK1 antibody. Mangiferin did not influence interaction of fluorescent LPS to toll-like receptor-4 on the macrophages. Molecular peak of mangiferin bound to IRAK1 was detected in the macrophages by mass analysis. Mangiferin (10 μM) inhibited LPS-stimulated expression of TNF-α, IL-1β and IL-6 by 81.0%, 89.5% and 88.3%, respectively, whereas it increased IL-10 expression by 131.8% compared to LPS-nontreated group. Mangiferin furthermore inhibited colon shortening, macroscopic score, and colonic myeloperoxidase activity in TNBS-induced colitic mice. Mangiferin inhibited TNBS-induced IRAK1 phosphorylation and NF-κB activation. Mangiferin suppressed TNBS-induced up-regulation of cyclooxygenase-2 and inducible NO synthase. Furthermore, mangiferin (20mg/kg) significantly inhibited TNF-α by 78%, IL-1β by 82%, and IL-6 expressions by 88% (P<0.05), but induced IL-10 expression to 79% of the normal control group (P<0.05). Based on these findings, mangiferin may ameliorate inflammatory diseases such as colitis by regulating NF-κB and MAPK signaling pathways through the inhibition of IRAK1 phosphorylation.
authors: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors: Jin-Ju
authors: JJ
authors: Jeong
authors: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Republic of Korea; Department of Food and Nutrition, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors: Se-Eun
authors: SE
authors: Jang
authors: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors: Supriya R
authors: SR
authors: Hyam
authors: Department of Food and Nutrition, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors: Myung Joo
authors: MJ
authors: Han
authors: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: dhkim@khu.ac.kr.
authors: Dong-Hyun
authors: DH
authors: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010457:Peptidoglycan; D010766:Phosphorylation / Q000187:drug effects; D014302:Trinitrobenzenesulfonic Acid; D044004:Xanthones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010457:Peptidoglycan; D044004:Xanthones; C013592:mangiferin; D014302:Trinitrobenzenesulfonic Acid; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse; D020928:Mitogen-Activated Protein Kinases
keywords: Colitis; IRAK1; MAP kinase; Macrophage; Mangiferin; NF-κB