Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, 173229, India.
Biogerontology. 2022 Dec;23(6):789-807. doi: 10.1007/s10522-022-09976-9. Epub 2022 Jul 2.
Age-dependent increased risk of inflammatory bowel diseases such as ulcerative colitis is being increasingly realized, and yet therapies targeting this disorder within the purview of aging are limited. The present study attempted to assess the efficacy of green tea epigallocatechin gallate (EGCG) consumption in preventing the severity and progression of dextran sulphate sodium (DSS)-induced ulcerative colitis in 18 months old middle-aged male mice. Acute colitis was induced in animals using DSS and protective effects of EGCG consumption were examined. Different parameters related to disease progression and molecular markers related to oxi-inflammatory stress, localized and systemic cytokine response, epithelial barrier integrity, and cell cycle progression profile were evaluated. DSS treatment induced rapid and severe symptoms of colitis such as consistently increased DAI score, shortened and inflamed colon accompanied by increased levels of inflammatory proteins (TNFα/IL-6/IL-1β) in both the colon tissue and cultured splenocytes indicating exaggerated Th1 immune response. Markers of oxidative stress increased while antioxidant defences and the expression of tight junction genes in the colonic cells were attenuated. Dysregulation in the expression of cell cycle inhibitory genes (p53/p21/p16) indicated possible induction of colitis-induced dysplasia. On the other hand, EGCG consumption strongly attenuated all the measured ostensible as well as molecular markers of the disease progression as evidenced by improved DAI score, cellular antioxidant capacity, attenuated Th1 cytokine response both in the colon and cultured splenocytes, enhanced expression of tight junction genes, and cell cycle inhibitors thereby suggesting systemic effects of EGCG. Together, these observations suggest that drinking EGCG-rich green tea can be a significant way of managing the severity of colitis during aging.
年龄依赖性炎症性肠病（如溃疡性结肠炎）的风险日益增加，但针对衰老相关疾病的治疗方法有限。本研究试图评估绿茶表没食子儿茶素没食子酸酯（EGCG）摄入对预防 18 个月大的中年雄性小鼠葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎严重程度和进展的疗效。通过 DSS 诱导动物急性结肠炎，检查 EGCG 摄入的保护作用。评估与疾病进展相关的不同参数和与氧化炎症应激、局部和全身细胞因子反应、上皮屏障完整性和细胞周期进展特征相关的分子标志物。DSS 处理诱导了快速和严重的结肠炎症状，如持续增加的 DAI 评分、缩短和发炎的结肠，同时伴有结肠组织和培养的脾细胞中炎症蛋白（TNFα/IL-6/IL-1β）水平升高，表明过度的 Th1 免疫反应。氧化应激标志物增加，而结肠细胞中的抗氧化防御和紧密连接基因的表达减弱。细胞周期抑制基因（p53/p21/p16）的表达失调表明可能诱导结肠炎诱导的发育不良。另一方面，EGCG 摄入强烈减弱了所有测量的明显的以及疾病进展的分子标志物，如 DAI 评分改善、细胞抗氧化能力增强、在结肠和培养的脾细胞中 Th1 细胞因子反应减弱、紧密连接基因表达增强、细胞周期抑制剂表达增强，从而提示 EGCG 的全身作用。总之，这些观察结果表明，饮用富含 EGCG 的绿茶可能是一种管理衰老过程中结肠炎严重程度的重要方法。
