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

Wei Dou, Jingjing Zhang, Gaiyan Ren, Lili Ding, Aning Sun, Chao Deng, Xiaojun Wu, Xiaohui Wei, Sridhar Mani, Zhengtao Wang

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)170-178
Number of pages9
JournalInternational Immunopharmacology
Volume23
Issue number1
DOIs
StatePublished - 2014

Fingerprint

Dextran Sulfate
NF-kappa B
Colitis
Mitogen-Activated Protein Kinases
Inflammatory Bowel Diseases
Tumor Necrosis Factor-alpha
Colon
Phosphorylation
mangiferin
Mangifera
Intercellular Adhesion Molecule-1
Interleukin-1
Reporter Genes
Nitric Oxide Synthase
Peroxidase
Transfection
Gastrointestinal Tract
Weight Loss
Diarrhea
Interleukin-6

Keywords

  • Dextran sulfate sodium
  • Inflammatory bowel disease
  • Mangiferin
  • MAPK
  • NF-κB

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology
  • Medicine(all)

Cite this

Mangiferin attenuates the symptoms of dextran sulfate sodium-induced colitis in mice via NF-κB and MAPK signaling inactivation. / Dou, Wei; Zhang, Jingjing; Ren, Gaiyan; Ding, Lili; Sun, Aning; Deng, Chao; Wu, Xiaojun; Wei, Xiaohui; Mani, Sridhar; Wang, Zhengtao.

In: International Immunopharmacology, Vol. 23, No. 1, 2014, p. 170-178.

Research output: Contribution to journalArticle

Dou, Wei ; Zhang, Jingjing ; Ren, Gaiyan ; Ding, Lili ; Sun, Aning ; Deng, Chao ; Wu, Xiaojun ; Wei, Xiaohui ; Mani, Sridhar ; Wang, Zhengtao. / Mangiferin attenuates the symptoms of dextran sulfate sodium-induced colitis in mice via NF-κB and MAPK signaling inactivation. In: International Immunopharmacology. 2014 ; Vol. 23, No. 1. pp. 170-178.
@article{07338f6f7d034403805ead0cf7ac5958,
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.",
keywords = "Dextran sulfate sodium, Inflammatory bowel disease, Mangiferin, MAPK, NF-κB",
author = "Wei Dou and Jingjing Zhang and Gaiyan Ren and Lili Ding and Aning Sun and Chao Deng and Xiaojun Wu and Xiaohui Wei and Sridhar Mani and Zhengtao Wang",
year = "2014",
doi = "10.1016/j.intimp.2014.08.025",
language = "English (US)",
volume = "23",
pages = "170--178",
journal = "International Immunopharmacology",
issn = "1567-5769",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Mangiferin attenuates the symptoms of dextran sulfate sodium-induced colitis in mice via NF-κB and MAPK signaling inactivation

AU - Dou, Wei

AU - Zhang, Jingjing

AU - Ren, Gaiyan

AU - Ding, Lili

AU - Sun, Aning

AU - Deng, Chao

AU - Wu, Xiaojun

AU - Wei, Xiaohui

AU - Mani, Sridhar

AU - Wang, Zhengtao

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Dextran sulfate sodium

KW - Inflammatory bowel disease

KW - Mangiferin

KW - MAPK

KW - NF-κB

UR - http://www.scopus.com/inward/record.url?scp=84907455018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907455018&partnerID=8YFLogxK

U2 - 10.1016/j.intimp.2014.08.025

DO - 10.1016/j.intimp.2014.08.025

M3 - Article

C2 - 25194678

AN - SCOPUS:84907455018

VL - 23

SP - 170

EP - 178

JO - International Immunopharmacology

JF - International Immunopharmacology

SN - 1567-5769

IS - 1

ER -