Drug Delivery Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
Department of Pharmaceutics, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, China.
Int J Mol Sci. 2023 Jun 29;24(13):10828. doi: 10.3390/ijms241310828.
The pathogenesis of ulcerative colitis (UC) is associated with inflammation, oxidative stress, and gut microbiota imbalance. Although most researchers have demonstrated the antioxidant bioactivity of the phenolic compounds in plants, their UC-curing ability and underlying mechanisms still need to be further and adequately explored. Herein, we studied the antioxidation-structure relationship of several common polyphenols in plants including gallic acid, proanthocyanidin, ellagic acid, and tannic acid. Furthermore, the in vivo effects of the plant polyphenols on C57BL/6 mice with dextran-sulfate-sodium-induced UC were evaluated and the action mechanisms were explored. Moreover, the interplay of several mechanisms was determined. The higher the number of phenolic hydroxyl groups, the stronger the antioxidant activity. All polyphenols markedly ameliorated the symptoms and pathological progression of UC in mice. Furthermore, inflammatory cytokine levels were decreased and the intestinal barrier was repaired. The process was regulated by the antioxidant-signaling pathway of nuclear-erythroid 2-related factor 2. Moreover, the diversity of the intestinal microbiota, Firmicutes-to-Bacteroides ratio, and relative abundance of beneficial bacteria were increased. An interplay was observed between microbiota regulation and oxidative stress, immunity, and inflammatory response. Furthermore, intestinal barrier repair was found to be correlated with inflammatory responses. Our study results can form a basis for comprehensively developing plant-polyphenol-related medicinal products.
溃疡性结肠炎(UC)的发病机制与炎症、氧化应激和肠道微生物失衡有关。尽管大多数研究人员已经证明了植物中酚类化合物的抗氧化生物活性,但它们治疗 UC 的能力及其潜在机制仍需要进一步充分探索。在此,我们研究了几种常见植物多酚(包括没食子酸、原花青素、鞣花酸和单宁酸)的抗氧化-结构关系。此外,还评估了植物多酚对葡聚糖硫酸钠诱导的 UC 模型 C57BL/6 小鼠的体内作用,并探讨了其作用机制。此外,还确定了几种机制的相互作用。酚羟基的数量越多,抗氧化活性越强。所有多酚都显著改善了 UC 小鼠的症状和病理进展。此外,炎症细胞因子水平降低,肠道屏障得到修复。该过程受核红细胞 2 相关因子 2 的抗氧化信号通路调节。此外,肠道微生物多样性、厚壁菌门到拟杆菌门的比例以及有益细菌的相对丰度增加。观察到微生物群调节与氧化应激、免疫和炎症反应之间存在相互作用。此外,还发现肠道屏障修复与炎症反应有关。我们的研究结果可以为全面开发植物多酚相关药物产品提供基础。