Hypoglycemic Activity Of Flavonoids From Citrus Fruits

Studies have shown that citrus fruits have many biological activities including hypoglycemic.In this study,the HepG2 cell-glucose consumption model was used to evaluate the glucose consumption activity of flavonoids in 35 different citrus fruits(flavedo,albedo,segment membrane,juice vesicle).The components of PMFs were isolated and purified from citrus fruits with strong glucose consumption activity,and their hypoglycemic activities were evaluated in vitro.RT-qPCR was used to analyze the differential expression of related senes.The self-style diabetic KK-Ay mice were further used to verify the hypoglycemic activities in vivo of PMFs.The main results are as follow.1.The glucose consurmption activities of flavonoids from different citrus cultivars differ greatly.The flavonoids extracted from different parts of the same variety have different potential hypoglycemic activities.Flavonoids which play the role of glucose consumption activities mainly come from flavedo and albedo,while the segment membrane and juice vesicle extracts failed to detect this activity.Therefore,the active component that exerts hypoglycemic action is mainly distributed in the citrus peel.Meanwhile,the citrus cultivars with potential hypoglycemic ability were screened out through related research:'OG','AY30','CZG','TC',etc.2.PMFs were isolated and purified from Citrus reticulate cv.Suavissima(Ougan)peel,and the hypoglycemic effect was studied in vitro.It was found that when the concentration of PMFs was 5?g/mL,the glucose consumption of HepG2 cells reached 3.86 mmol/L for 24 h,which was 1.48 times of that of negative control group.RT-qPCR analysis showed that PMFs could promote glucose consumption in HepG2 cells by activating WNT signaling pathway.PMFs could significantly up-regulate the expression of TCF7L2 and inhibit the expression of SMAD3 and DKK1,which were key factors of WNT signaling pathway.3.Glucose-regulating activity in vivo of PMFs in citrus fruits was evaluated.The results showed that PMFs in citrus fruits(15 mg/kg)showed significant hypoglycemic effect in diabetic KK-Ay mice.In the third week of administration,the fasting blood glucose of PMFs group was significantly lower than that of model group(13.38 mmol/L vs 22.02 mmol/L),and the hypoglycemic effect of PMFs could be maintained by continuous observation until the fifth week.It was also found that feeding PMFs could significantly improve the oral glucose tolerance of diabetic KK-Ay mice.In addition,the serum levels of high density lipoprotein cholesterol(HDL-c),adiponectin and the AST/ALT ratio were significantly increased,while the serum triglycerides(TG),aminotransferase(ALT)level as well as liver weight of diabetic KK-Ay mice were significantly reduced.H&E staining and oil red O staining showed that PMFs could effectively alleviate hepatic steatosis and reduces the size and number of lipid droplets in liver cells.Therefore,PMFs compounds from citrus fruits can effectively improve glycolipid metabolism in diabetic KK-Ay mice.In conclusion,this study screened out citrus varieties with potential hypoglycemic ability,and found that PMFs compounds in peel were the main hypoglycemic active ingredients.Experiments in vitro and in vivo showed that PMFs compounds in Citrus could effectively improve glycolipid metabolism and affect the expression of related genes in WNT signaling pathway.Our findings may provide theoretical basis for in-depth study of the hypoglycemic effect of citrus fruits,and also provide theoretical basis and technical support for the development and utilization of high value-added citrus products.