Resveratrol Ameliorates Intestinal Barrier Defects and Inflammation in Colitic Mice and Intestinal Cells
Yunika Mayangsari1,2, Takuya Suzuki1
1Department of Biofunctional Science and Technology, Graduate School of Biosphere Science , Hiroshima University , Kagamiyama, Higashi Hiroshima City 739-8528 , Japan.
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.
Insights
Resveratrol supplementation ameliorates dextran sodium sulfate (DSS)-induced colitis by reducing neutrophil infiltration and restoring tight junction (TJ) barriers. This natural compound mitigates inflammatory responses in both mouse models and intestinal cells, offering a potential therapeutic strategy for colitis.
Area of Science:
- Gastroenterology
- Molecular Biology
- Pharmacology
Background:
- Inflammatory bowel disease (IBD), including colitis, is characterized by chronic inflammation of the gastrointestinal tract.
- Disruption of intestinal epithelial barrier integrity, marked by compromised tight junctions (TJs), is a key feature of colitis.
- Neutrophil infiltration into the colonic mucosa contributes significantly to tissue damage during colitis.
Purpose of the Study:
- To investigate the therapeutic potential of resveratrol in mitigating dextran sodium sulfate (DSS)-induced colitis.
- To elucidate the mechanisms underlying resveratrol's effects, focusing on neutrophil infiltration and intestinal tight junction (TJ) barrier function.
- To evaluate resveratrol's impact on inflammatory signaling pathways in intestinal cells.
Main Methods:
- Induction of colitis in a mouse model using dextran sodium sulfate (DSS).
- Administration of resveratrol via diet to treated mice.
- Assessment of clinical parameters including body weight, colon length, and histological analysis.
- Measurement of pro-inflammatory cytokines (IL-1β, IL-6, CXCL-2) and TJ proteins (occludin) in colonic tissues.
- In vitro studies using Caco-2 intestinal cells treated with TNF-α and resveratrol to assess IL-8 production and inflammatory signaling pathways (NF-κB, ERK, JNK).
Main Results:
- DSS-induced colitis resulted in significant body weight loss, colon shortening, increased pro-inflammatory cytokines (IL-1β, IL-6, CXCL-2), decreased TJ proteins (occludin), and elevated neutrophil infiltration.
- Resveratrol supplementation partially or completely reversed these DSS-induced pathological changes.
- In Caco-2 cells, resveratrol suppressed TNF-α-induced IL-8 production and attenuated the phosphorylation of key inflammatory signaling molecules (NF-κB, ERK, JNK).
Conclusions:
- Resveratrol demonstrates significant ameliorative effects against DSS-induced colitis in mice.
- The protective mechanisms involve the restoration of intestinal tight junction (TJ) barrier integrity and reduction of neutrophil infiltration.
- Resveratrol's ability to modulate inflammatory signaling pathways in intestinal cells contributes to its therapeutic efficacy in colitis.
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