Studies On Citrus Flavonoids On The Regulation Of Blood Glucose And Its Hypoglycemic Mechanisms

Diabetes mellitus has become one of the three diseases that endangers human health. Due to the unscientific diet, more and more people in the world are suffering diabetes. Therefore, diet therapy is one of the effective measures to manage hyperglycemia. Flavonoids are a class of important bioactive natural products and are being extensively used in functional foods. In the present study, we studied the usage of four citrus flavonoids (i.e., hesperidin, naringin, neohesperidin and nobiletin) as specific nutrients in functional foods and its blood glucose regulation mechanisms.Firstly, the spectroscopy experiments results of starch-iodine complex showed that all the tested citrus flavonoids significantly inhibited amylase-catalyzed soluble starch digestion. Moreover, the four citrus flavonoids could occupy the helix structure of amylose, thus inhibited amylose digestion, whereas hesperidin and nobiletin inhibited both amylose and amylopectin digestion. However, these flavonoids showed weak inhibitory activities against digestive enzymes (e.g., pancreatic α-amylase and α-glucosidase).Beside, molecular docking results showed that these flavonoids could activate GK activity, which might promote glycolysis and increase the glucose utilization of liver. Moreover, citrus flavonoids inhibited the activity of GSK-3β, which might enhance the activity of glycogen synthase. Thereby resulted in promoting glycogen synthesis, improving liver glucose utilization. The PPAR y docking results indicated that hesperidin and naringin range between full agonists and part agonists, while nobiletin and neohesperidin belong to part agonists. Furthermore, hesperidin, naringin, and neohesperidin showed DPP IV inhibitory activity.Then, confirming experiments were conducted. HepG2cells experiments indicated that50μM citrus flavonoids exhibited low toxicity to cells. The results illustrated that glucose consumption, glycogen concentration and glucokinase activity were significantly elevated and glucose-6-phosphatase activity was markedly decreased by citrus flavonoids.These results demonstrate that citrus flavonoids play important roles in preventing the progression of hyperglycemia, partly by binding to starch, increasing hepatic glycolysis and glycogen concentration and lowering hepatic gluconeogenesis. This work suggests that citrus flavonoids might be potentially used for prevention of postprandial hyperglycemia.