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Resveratrol Ameliorates Intestinal Barrier Defects and Inflammation in Colitic Mice and Intestinal Cells

Author:
Mayangsari, Yunika, Suzuki, Takuya
Source:
Journal of agricultural and food chemistry 2018 v.66 no.48 pp. 12666-12674
ISSN:
1520-5118
Subject:
animal models, body weight changes, colitis, colon, diet, human cell lines, inflammation, interleukin-1beta, interleukin-6, interleukin-8, ligands, mice, mitogen-activated protein kinase, neutrophils, occludins, phosphorylation, resveratrol, tight junctions, tissues, transcription factor NF-kappa B, tumor necrosis factor-alpha
Abstract:
This study is aimed to investigate the ameliorative effect of resveratrol in a dextran sodium sulfate (DSS)-induced colitis mouse model and intestinal Caco-2 cells, focusing on neutrophil infiltration and tight junction (TJ) barriers. DSS administration caused body weight loss (day8, control 104 ± 1, DSS 72 ± 2%, p < 0.05), shortening of colon length (control 5.1 ± 0.1, DSS 3.8 ± 0.1 cm, p < 0.05), pro-inflammatory cytokines increase—including interleukin (IL)-1β (control 1.0 ± 0.2, DSS 58.5 ± 29.6 arbitrary unit (AU), p < 0.05), IL-6 (control 1.0 ± 0.3, DSS 312 ± 82 AU, p < 0.05), and chemokine motif ligand 2 (CXCL-2, a murine IL-8 homologue, control 1.0 ± 0.4, DSS 696 ± 262 AU, p < 0.05), decreased TJ proteins (e.g., occludin, control 1.0 ± 0.05, DSS 0.11 ± 0.03 AU, p < 0.05), and neutrophil infiltration (control 1.2 ± 0.2, DSS 25.9 ± 1.1 cells, p < 0.05). Supplemental resveratrol (0.1% (w/w) in the diet) partially or totally reversed these symptoms (body weight change 100 ± 1, colon length 4.6 ± 0.1; IL-1β 5.9 ± 1.8, IL-6 10 ± 3, CXCL-2 14 ± 7, occludin 0.76 ± 0.06, neutrophil infiltration 9.3 ± 0.7, p < 0.05). Pretreatment of intestinal Caco-2 cells with resveratrol suppressed the TNF-α-induced production of IL-8 (control 1.00 ± 0.04, TNFα 3.40 ± 0.16, TNFα+Res 1.81 ± 0.28 AU, p < 0.05) and phosphorylation of the inflammatory signaling molecules including NF-κB, extracellular signal-regulated kinase and stress c-Jun N-terminal protein kinase. Collectively, the reduction of TJ barrier defect and IL-8 in intestinal cells, leading to reduced neutrophil infiltration into colonic tissues, appears to be one of the central mechanisms for the resveratrol-mediated effect.
Agid:
6247740