Su Hongming, Mo Jianling, Ni Jingdan, Ke Huihui, Bao Tao, Xie Jiahong, Xu Yang, Xie Lianghua, Chen Wei
Department of Food Science and Nutrition, National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, China.
Department of Traditional Chinese Medicine, Sir Run Run Shaw Hospital, School of Medcine, Zhejiang University, Hangzhou 310016, China.
Oxid Med Cell Longev. 2020 Jul 23;2020:6538930. doi: 10.1155/2020/6538930. eCollection 2020.
Accumulating evidence indicates that type 2 diabetes (T2D) is associated with intestinal barrier dysfunction and dysbiosis, implying the potential targets for T2D therapeutics. Andrographolide was reported to have several beneficial effects on diabetes and its associated complications. However, the protective role of andrographolide, as well as its underlying mechanism against T2D, remains elusive. Herein, we reported that andrographolide enhanced intestinal barrier integrity in LPS-induced Caco-2 cells as indicated by the improvement of cell monolayer barrier permeability and upregulation of tight junction protein expression. In addition, andrographolide alleviated LPS-induced oxidative stress by preventing ROS and superoxide anion radical overproduction and reversing glutathione depletion. In line with the results, andrographolide reduced metabolic endotoxemia and strengthened gut barrier integrity in db/db diabetic mice. We also found that andrographolide appeared to ameliorate glucose intolerance and insulin resistance and attenuated diabetes-associated redox disturbance and inflammation. Furthermore, our results indicated that andrographolide modified gut microbiota composition as indicated by elevated Bacteroidetes/Firmicutes ratio, enriched microbial species of , and increased SCFAs level. Taken together, this study demonstrated that andrographolide exerted a glucose-lowering effect through strengthening intestinal barrier function and increasing the microbial species of , which illuminates a plausible approach to prevent T2D by regulating gut barrier integrity and shaping intestinal microbiota composition.
越来越多的证据表明，2型糖尿病（T2D）与肠道屏障功能障碍和肠道菌群失调有关，这意味着T2D治疗有潜在靶点。据报道，穿心莲内酯对糖尿病及其相关并发症有多种有益作用。然而，穿心莲内酯对T2D的保护作用及其潜在机制仍不清楚。在此，我们报道穿心莲内酯可增强脂多糖诱导的Caco-2细胞的肠道屏障完整性，表现为细胞单层屏障通透性的改善和紧密连接蛋白表达的上调。此外，穿心莲内酯通过防止活性氧（ROS）和超氧阴离子自由基过量产生以及逆转谷胱甘肽耗竭来减轻脂多糖诱导的氧化应激。与这些结果一致，穿心莲内酯降低了db/db糖尿病小鼠的代谢性内毒素血症并增强了肠道屏障完整性。我们还发现穿心莲内酯似乎改善了葡萄糖不耐受和胰岛素抵抗，并减轻了糖尿病相关的氧化还原紊乱和炎症。此外，我们的结果表明，穿心莲内酯改变了肠道微生物群组成，表现为拟杆菌门/厚壁菌门比例升高、特定微生物种类富集以及短链脂肪酸水平增加。综上所述，本研究表明穿心莲内酯通过增强肠道屏障功能和增加特定微生物种类发挥降糖作用，这为通过调节肠道屏障完整性和塑造肠道微生物群组成来预防T2D提供了一种可行的方法。
