Abstract
Diabetes is a metabolic complication distinguished mainly by persistent hyperglycemia and is involved in the formation of reactive oxygen species, thereby causing oxidative stress, which is the major culprit for diabetic complications in different organs, including the vascular system. Controlling blood glucose is the most effective strategy for preventing diabetes and its complications. Currently, the available antidiabetic therapy is associated with several side effects, thus inexhaustible attention has been paid toward the development of natural compounds. The present review highlights the different types of flavonoids as potent antidiabetic agents along with their structure-activity relationship (SAR) studies, which will definitely aid in designing innovative molecules with improved antidiabetic efficacy. The type of substitution in the flavonoid core structure decides their bindings at different biological targets involved in diabetes development such as xanthine oxidase inhibitors, SGLT-II inhibitors, a-glucosidase inhibitors, PPAR-gamma agonists, DPP-4 inhibitors, and glycogen phosphorylase inhibitors. Based on SAR investigation, a double bond between C-2 and C-3 positions, hydroxy substitutions at C-5 and C-7 positions of ring A, and substitution by the ketonic group at the C-4 position were considered as lead modifications in the bioactivity of flavonoids for potent antidiabetic activity.