Anti-Diabetic Activity Evaluation Of Prenylated Chalcones And Dihydroflavones

Humulus lupulus (hops) contains a variety of active ingredients, in which flavonoids is one of the important representative of the active substances. Prenylated chalcones and dihydroflavones are the unique flavonoids in hops. The low content of prenylated chalcones and dihydroflavones in hops limits its development and application. In this study, natural prenylated chalcones and dihydroflavones in hops were synthesized and examined in vivo and in vitro anti-diabetic activities.Two prenylated chalcones (3’-prenylchalconaringenin, 3’-geranylchalconaringenin) and two dihydroflavones (8-prenylnaringenin, 8-geranylnaringenin) were obtained by MOM protection, halogen substitution, aldol condensation and MOM protection from 2,4,6-trihydroxyacetophenone and naringin. a-Glucosidase inhibitory activity was evaluated in vitro. 3’-Geranylchalconaringenin (2) inhibited a-glucosidase (IC50 = 1.08 μM) with activity 50-fold higher than acarbose (IC50 = 51.30 μM) and showed moderate inhibitory activity against a-amylase (IC50 = 20.46 μM). Enzyme inhibition mechanism studies have shown that 2 competitively and irreversibly inhibited a-glucosidase and directly bound to a-glucosidase.Docking analysis also substantiated that there are a strong hydrogen bond and hydrophobic interaction between compound 2 and α-glucosidase and has a good affinity for the active pocket of a-glucosidase.In addition, anti-diabetic activity of 3’-geranylchalconaringenin (2) was evaluated in vivo with type 2 diabetes mellitus mice model which induced by streptozotocin (STZ) and fed with high-fat-diet. The results suggested that compound 2 slight differently change in evaluating indicators of food intake, water intake and body weight compared with negative control. In addition, compound 2 suppressed the increase of postprandial blood glucose levels and serum levels of total cholesterol and triglycerides in streptozotocin-induced diabetic mice.Taken together, these results suggest that 3’-geranylchalconaringenin has dual inhibitory activity against a-glucosidase and a-amylase and alleviates diabetic hyperglycemia and hyperlipidemia, making it a potential functional food ingredient and drug candidate for management of type 2 diabetes.