Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University.
Taicang Hospital of Traditional Chinese Medicine.
Biol Pharm Bull. 2020;43(3):450-457. doi: 10.1248/bpb.b19-00786.
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 pathway-related 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 DSS-induced IBD by modulating SUMO1 through Wnt/β-catenin pathway.
白藜芦醇（Res）是一种天然的活性抗氧化剂，可有效缓解炎症性肠病（IBD）。但是，其功能的具体机制尚不清楚。在我们的研究中，构建了葡聚糖硫酸钠（DSS）诱导的小鼠 IBD 疾病模型。所有小鼠随机分为三组。通过观察体重、粪便特征、结肠/脾脏大体外观、组织苏木精-伊红（H＆E）/免疫组织化学（IHC）和炎症因子，评估白藜芦醇对 IBD 的治疗作用。通过免疫组织化学，Western blot，实时 PCR（RT-PCR）和免疫荧光分析小泛素样修饰蛋白 1（SUMO1）及其 Wnt /β-连环蛋白途径相关基因的表达。结果表明，白藜芦醇治疗可显著缓解 IBD 症状。白藜芦醇治疗的小鼠结肠和脾脏组织中抗炎细胞因子的表达水平升高，促炎细胞因子的表达水平降低。白藜芦醇治疗的 IBD 小鼠的结肠和脾脏组织中 SUMO1 表达和 Wnt /β-连环蛋白途径受到抑制。此外，我们提供了证据表明白藜芦醇抑制了人结肠上皮细胞系（FHC）中 SUMO1 和β-连环蛋白的表达及其核定位。而且，我们发现结直肠癌患者的 SUMO1 和β-连环蛋白表达水平高于健康人和结肠炎患者。总之，白藜芦醇通过 Wnt /β-连环蛋白途径调节 SUMO1 来减轻 DSS 诱导的 IBD。
