College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China.
National Engineering Research Center of JUNCAO Technology, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China.
Food Funct. 2022 Mar 21;13(6):3572-3589. doi: 10.1039/d2fo00021k.
Flavonoid compounds such as luteolin exhibit hypolipidemic effects, and there are few reports on the hypoglycemic activity of luteolin derivatives. In this research, 6,8-(1,3-diaminoguanidine) luteolin (DAGL) and its Cr complex (DAGL·Cr) were obtained as a result of structural modifications to luteolin, and the hypoglycemic activities and the composition of intestinal microbiota in T2DM mice were investigated. This study found that DAGL and DAGL·Cr could significantly restore body weight, FBG, OGTT, AUC, and GSP in T2DM mice. Moreover, the pancreatic islet function index and the biochemical indicators of serum and the liver were also significantly improved. The histopathological results also showed that DAGL and DAGL·Cr had a stronger repair ability in the liver and the pancreas. It was also revealed that the potential hypoglycemic mechanism of DAGL and DAGL·Cr was involved in the simultaneous regulation of PI3K/AKT-1/GSK-3β/GLUT-4 and PI3K/AKT-1/mTOR/S6K1/IRS-1. Furthermore, DAGL and DAGL·Cr could also regulate the structure of the intestinal microbiota and increase the content of SCFA to relieve the symptoms of hyperglycemia in T2DM mice. This included a significant reduction in the ratio of Firmicutes and Bacteroidetes (F/B), and at the genus level, an increase in the relative abundance of and , and improvement in the content of SCFA in the feces of T2DM mice. In conclusion, in this study, DAGL and DAGL·Cr were found to improve hyperglycemia in T2DM mice by improving the pancreatic islet function index, regulating the biochemical indicators of serum and the liver, repairing damaged tissues, and regulating the PI3K/AKT-1 signaling pathway as well as reducing F/B, increasing the relative abundance of intestinal beneficial microbiota, and the content of SCFA in the feces. The hypoglycemic effect of DAGL·Cr on the body weight, serum IL-10, serum IL-6, and pancreatic islet function index was significantly better than that of DAGL.
类黄酮化合物如木犀草素具有降血脂作用，而关于木犀草素衍生物的降血糖活性的报道较少。在这项研究中，6,8-(1,3-二氨基胍基)木犀草素(DAGL)及其铬配合物(DAGL·Cr)是通过对木犀草素进行结构修饰得到的，并研究了它们在 T2DM 小鼠中的降血糖活性和肠道微生物组成。研究发现，DAGL 和 DAGL·Cr 可显著恢复 T2DM 小鼠的体重、FBG、OGTT、AUC 和 GSP。此外，胰岛功能指数以及血清和肝脏的生化指标也得到了显著改善。组织病理学结果还表明，DAGL 和 DAGL·Cr 对肝脏和胰腺具有更强的修复能力。研究还表明，DAGL 和 DAGL·Cr 的潜在降血糖机制涉及同时调节 PI3K/AKT-1/GSK-3β/GLUT-4 和 PI3K/AKT-1/mTOR/S6K1/IRS-1。此外，DAGL 和 DAGL·Cr 还可以调节肠道微生物群的结构，增加 SCFA 的含量，以缓解 T2DM 小鼠的高血糖症状。这包括显著降低厚壁菌门和拟杆菌门（Firmicutes 和 Bacteroidetes）的比例（F/B），在属水平上，增加相对丰度和，以及改善 T2DM 小鼠粪便中 SCFA 的含量。总之，在这项研究中，DAGL 和 DAGL·Cr 通过改善胰岛功能指数、调节血清和肝脏的生化指标、修复受损组织、调节 PI3K/AKT-1 信号通路以及降低 F/B、增加有益肠道微生物群的相对丰度和粪便中 SCFA 的含量来改善 T2DM 小鼠的高血糖。DAGL·Cr 对体重、血清 IL-10、血清 IL-6 和胰岛功能指数的降血糖作用明显优于 DAGL。
