Therapeutic Potential of Selected Flavonoids as Natural Antidiabetic Agents

Type 2 diabetes mellitus (T2DM) remains a major clinical challenge, with postprandial hyperglycemia (PPG) playing a key role in the development of vascular complications. Current pharmacotherapies often do not sufficiently control PPG, highlighting the need for complementary strategies. One effective approach is the inhibition of carbohydrate digesting enzymes, α-amylase and α-glucosidase, which delays glucose absorption and reduces PPG excursions. Flavonoids, a diverse class of plant-derived polyphenols, exhibit multiple biological activities relevant to T2DM, including enzyme inhibition, antioxidant, and anti-inflammatory effects. This review summarizes the mechanisms by which flavonoids modulate glucose metabolism, with particular emphasis on their interactions with α-amylase and α-glucosidase. Structure-activity relationships are discussed, focusing on the influence of hydroxylation patterns, conjugation, and molecular planarity on inhibitory potency and selectivity. Selected flavonoids-chrysin, apigenin, luteolin, and quercetin-are comparatively analyzed in terms of enzyme inhibition profiles, binding mechanisms, and selectivity. Evidence from in vitro studies, enzyme kinetics, and molecular docking highlights their differential activity, particularly the preferential inhibition of α-glucosidase over α-amylase, which may reduce gastrointestinal side effects. Overall, flavonoids represent promising modulators of PPG. However, their clinical relevance is limited by bioavailability and variability of experimental data, warranting further investigation.