Flavonoids from Ougan (Citrus suavissima Hort. ex Tanaka) peel exert hypoglycemic potency through inhibiting insulin resistance in HepG2 cells and regulating gut microbiota in diabetic mice

To fully and value-addedly utilize the citrus peel resource, flavonoids were extracted and purified from peel powder of Ougan ( Citrus suavissima Hort. ex Tanaka) using an ultrasonic assisted ethanol solution extraction method and AB-8 macroporous resin purification. The obtained flavonoid extract from peel of Ougan (FEPO) was used for the hypoglycemic experiments in vitro and in vivo on glucose consumption in insulin resistance model HepG2 cells and streptozotocin induced diabetes model mice. A significant reduction of glucose consumption in the model cells while a significant increase in the treated were found in a dose-dependent manner, compared to 5.2241 ± 0.2201 mmol/L of the normal cells ( P < 0.05). When the FEPO concentration was 80 μg/mL, the cell glucose consumption was 4.4055 ± 0.1772 mmol/L. Compared with those in the model group (diabetic mice), the fasting blood glucose in the FEPO intervened mice was significantly decreased ( P < 0.05). FEPO intervention caused decreased levels of TC, TG, LDL-C, and increased HDL-C and insulin contents in the serums as well as ameliorative histopathology of the liver, kidney, and pancreas in diabetic mice. FEPO improved the gut microbiota structure of diabetic mouse by regulating its composition, especially significantly increasing the relative abundance of Lactobacillus , Ileibacterium , unclassified_f_Lachnospiracea , Romboutsia , norank_f_Muribaculaceae , Faecalibaculum and Coriobacteriaceae_UCG-002 ( P < 0.05), while decreasing that of norank_f_norank_o_Clostridia_UCG-014 , Lachnospiraceae_NK4A136_group and Candidatus_Saccharimonas . In conclusion, FEPO had good hypoglycemic efficacies both in vitro and in vivo as well as gut microbiota regulating effect. • FEPO promoted glucose consumption and inhibited insulin resistance in IR-HepG2 cells. • FEPO effectively alleviated abnormal physical and blood indices and histopathology of diabetic mice. • FEPO ameliorated the gut microbiota structure of diabetic mouse by regulating its composition. • FEPO exerted hypoglycemic potency through inhibiting insulin resistance and regulating gut microbiota.