Protective effect of galangin against dextran sulfate sodium (DSS)-induced ulcerativecolitis in Balb/c mice

被引:57
|
作者
Sangaraju, Rajendra [1 ,2 ]
Nalban, Nasiruddin [1 ,2 ]
Alavala, Sateesh [1 ]
Rajendran, Vinoth [1 ]
Jerald, Mahesh Kumar [3 ]
Sistla, Ramakrishna [1 ,2 ]
机构
[1] CSIR Indian Inst Chem Technol IICT, Dept Appl Biol, Hyderabad 500007, Andhra Pradesh, India
[2] Acad Sci & Innovat Res AcSIR, CSIR HRDC Campus,Sect 19, Ghaziabad 201002, Uttar Pradesh, India
[3] CSIR Ctr Cellular & Mol Biol CCMB, Anim House Facil, Hyderabad 500007, Andhra Pradesh, India
关键词
Galangin; Ulcerative colitis; Inflammation; NF-kappa B pathway; Dextran sulfate sodium; CISPLATIN-INDUCED NEPHROTOXICITY; NRF2 SIGNALING PATHWAY; OXIDATIVE STRESS; INFLAMMATION; APOPTOSIS; ERK; GLUTATHIONE; MECHANISM; CYTOKINES; COLITIS;
D O I
10.1007/s00011-019-01252-w
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Objective and designInflammatory bowel disease (IBD) is known to cause chronic inflammation in the digestive tract by the immune malfunction. Herein, we demonstrate the protective effect of galangin (GAL), a phytochemical, on LPS-induced inflammation in cultured mouse macrophages (RAW 264.7) and the treatment of DSS-induced ulcerative colitis in Balb/c mice. However, the anti-inflammatory effect of GAL in DSS-exposed experimental colitis has not been investigated.Materials and methodsWe determined the levels of proinflammatory cytokines by ELISA, biochemical analysis using standard protocols and protein expression level of NF-kappa B signaling pathway and activation of Nrf2 gene pathway wereanalyzed by western blot analysis in colitis-induced mice.ResultsOur in vitro studies showed that LPS-stimulated RAW 264.7 cells treated with GAL reduced the levels of nitrites, IL-6, and TNF-alpha in a concentration-dependent manner. The results demonstrated that oral administration of GAL at 20mg/kg (lower dose) and 40mg/kg (higher dose) significantly reduced the severity of colitis and mitigated the clinical signs of both macroscopic and microscopic of the disease. The levels of proinflammatory cytokines (TNF-alpha and IL-6) in colonic tissue and serum were reduced significantly and in GAL+DSS-treated group relative to DSS alone treated group. Increased levels of anti-inflammatory cytokine (IL-10) was detected in colon tissues in GAL+DSS-treated groups relative to DSS alone treated group. We also observed decreased levels of myeloperoxidase (MPO), nitrites and TBARS with increased SOD in colonic tissue of GAL+DSS group. Besides, GAL+DSS-treated animals significantly suppressed protein expressions of p-NF-kappa B and p-Ikk-beta alpha, COX-2, iNOS, Nrf2 and increased HO-1 levels in colon tissues by inhibiting inflammation and oxidative stress.ConclusionOur study highlights the protective effect of galangin as an anti-inflammatory agent against the severe form of colitis in pre-clinical models suggesting its potency for the treatment of IBD in humans.
引用
收藏
页码:691 / 704
页数:14
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