Amelioration of type 2 diabetes by the novel 6, 8-guanidyl luteolin quinone-chromium coordination via biochemical mechanisms and gut microbiota interaction

Luteolin is a plant-derived flavonoid that exhibits a broad range of pharmacological activities. Studies on luteolin have mainly focused on its use for hyperlipidaemia prevention, whereas the capacity of the flavonoid to hinder hyperglycaemia development remains underexplored. To probe the anti-hyperglycemic mechanism of 6,8-guanidyl luteolin quinone-chromium coordination (GLQ.Cr), and to assess its regulatory effect on intestinal microbiota in type 2 diabetes mellitus (T2DM) mice. High-sucrose/high-fat diet-induced and intraperitoneal injection of streptozotocin was used to develop a T2DM model. Glycometabolism related indicators, histopathology, and gut microbiota composition in caecum samples were evaluated, and RNA sequencing (RNA-seq) of liver samples was conducted. Faecal microbiota transplantation (FMT) was further used to verify the anti-hyperglycemic activity of intestinal microbiota. The administration of GLQ.Cr alleviated hyperglycaemia symptoms by improving liver and pancreatic functions and modulating gut microbe communities (Lactobacillus, Alistipes, Parabacteroides, Lachnoclostridium, and Desulfovibrio). RNA-seq analysis showed that GLQ.Cr mainly affected the peroxisome proliferative activated receptor (PPAR) signalling pathway in order to regulate abnormal glucose metabolism. FMT significantly modulated the abundance of Lactobacillus, Alloprevotella, Alistipes, Bacteroides, Ruminiclostridium, Brevundimonas and Pseudomonas in the caecum to balance blood glucose levels and counteract T2DM mice inflammation. GLQ.Cr improved the abnormal glucose metabolism in T2DM mice by regulating the PPAR signalling pathway and modulating intestinal microbial composition. FMT can improve the intestinal microecology of the recipient and in turn ameliorate the symptoms of T2DM-induced hyperglycaemia.