Natural Prenylchalconaringenins and Prenylnaringenins as Antidiabetic Agents: α-Glucosidase and α-Amylase Inhibition and in Vivo Antihyperglycemic and Antihyperlipidemic Effects

Inhibition of alpha-glucosidase and alpha-amylase decreases postprandial blood glucose levels and delays glucose absorption, making it a treatment strategy for type 2 diabetes. This study examined in vivo and in vitro antidiabetic activities of natural prenylchalconaringenins 1 and 2 and prenylnaringenins 3 and 4, found in hops and beer. 3'-Geranylchalconaringenin (2) competitively and irreversibly inhibited alpha-glucosidase (IC50 = 1.08 mu M) with activity 50-fold higher than that of acarbose (IC50 = 51.30 mu M) and showed moderate inhibitory activity against a-amylase (IC50 = 20.46 mu M). Docking analysis substantiated these findings. In addition, compound 2 suppressed the increase in postprandial blood glucose levels and serum levels of total cholesterol and triglycerides in streptozotocin-induced diabetic mice. Taken together, these results suggest that 2 has dual inhibitory activity against alpha-glucosidase and alpha-amylase and alleviates diabetic hyperglycemia and hyperlipidemia, making it a potential functional food ingredient and drug candidate for management of type 2 diabetes.