Resveratrol Attenuates Inflammatory Bowel Disease in Mice by Regulating SUMO1

Abstract

Resveratrol (Res) is a natural active antioxidant that is effective in relieving inflammatory bowel disease (IBD). However, the specific mechanism for its function is unknown. In our study, dextran sodium sulfate (DSS)-induced mouse IBD disease model was constructed. All mice were randomly divided into three groups. The treatment effects of resveratrol on IBD were evaluated by observing the body weight, fecal traits, colon/ spleen gross appearance, tissue hematoxylin-eosin (H&E)/immunohistochemistry (IHC) and inflammatory factors. The expression of small ubiquitin-like modifier protein 1 (SUMO1) and its Wnt/β-catenin pathwayrelated genes was analyzed by IHC, Western blot, Real-time PCR (RT-PCR) and Immunofluorescence. The outcome indicated that resveratrol treatment significantly relieved the symptoms of IBD. The expression level of anti-inflammatory cytokines was increased while that of pro-inflammatory cytokines was decreased in both colon and spleen tissues of resveratrol-treated mice. SUMO1 expression and Wnt/β-catenin pathway were suppressed in colon and spleen tissues of IBD mice treated with resveratrol. In addition, we provided evidence that resveratrol inhibited SUMO1 and β-catenin expression and their nuclear localization in human colonic epithelial cell line (FHC). Moreover, we found that SUMO1 and β-catenin had higher expression levels in colorectal cancer patients than in health and colitis patients. In conclusions, resveratrol alleviates DSSinduced IBD by modulating SUMO1 through Wnt/β-catenin pathway.

Resveratrol and Resveratrol-Aspirin Hybrid Compounds as Potent Intestinal Anti-Inflammatory and Anti-Tumor Drugs

“…Furthermore, we can demonstrate significant alleviation of intestinal inflammation and inhibition of tumor growth with several aspirin-resveratrol derivatives (Figures 5 and 6A). Previous reports have confirmed our observations including a recent publication by Sudha et al (2020) [52] to demonstrate tumor reduction by resveratrol and publications by Wang et al (2019) [53] and Zhang et al (2019) [54] that demonstrated the beneficial effect of resveratrol on DSS-induced colitis but at 80,100 mg/kg resveratrol use. In addition, cell-based modulation of follicular tumorigenesis (at 300 µM) [55] highlights the importance of our findings at 50-100 µM for our resveratrol derivatives.…”

Resveratrol Alleviates Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis in Mice by Mediating PI3K/Akt/VEGFA Pathway

“…showed that RSV treatment significantly inhibited the severity of UC and dramatically reduced the expressions of TNF-α, IL-8, IFN-γ, p22, and gp91 relative to the UC control group, highlighting the antioxidant effects of RSV on preventing oxidative damage induced by DSS ( Yao et al, 2010 ). IL-10 serves as an anti-inflammatory cytokine, which is increased after RSV administration in inflammatory bowel disease ( Wang J. et al, 2020 ).…”

Resveratrol Suppresses Cross-Talk between Colorectal Cancer Cells and Stromal Cells in Multicellular Tumor Microenvironment: A Bridge between In Vitro and In Vivo Tumor Microenvironment Study

“…Indeed, it was reported that down-regulation of Sirt1 at least partially suppressed the effects of resveratrol-promoting chemopreventive and anti-tumorigenic effects in CRC cells [ 36 ]. In addition, resveratrol has also been shown to downregulate inflammation in colorectal cancer by suppressing the expression of SUMO1 (small ubiquitin-like modifier protein 1) and nuclear translocation, thereby suppressing the Wnt/β catenin pathway [ 77 ].…”