The objective of this review is to summarize knowledge on the inhibitory effects (IEs) of flavonoids on α-amylase (αA) and α-glucosidase (αG) relevant to the search of substitutes of acarbose (Aca). Flavonoids reported to be more effective at inhibiting αG than Aca have been summarized. The concept of "relative coefficient to Aca (RCAca)" has been proposed to integrate data from various reports. Correlations between hydrogen bond donors (H-donors), hydrogen bond acceptors (H-acceptors), partition coefficient values (XLog P3), and RCAca are discussed. Two kinds of binding modes between flavonoids and enzymes have been observed: (i) flavonoids directly bind to amino acid residues (AARs) in the active sites of enzymes and exclude the binding of substrate; (ii) flavonoids interact with AARs near the active site and close the channel to the active center. Some groups are correlated with stronger IEs: (i) substitutions of caffeoyl, galloyl, and prenyl groups in flavonoids enhance IEs; (ii) steric hindrance attenuates IEs, and linear molecules tend to be stronger inhibitors of porcine pancreatic αA (PPA). Whilst many achievements have been made, our understanding of the combined effects of different flavonoids, and flavonoids and Aca, remain ambiguous, and the effects of food matrices and stomach digestion on IEs of flavonoids are poorly understood. This review provides a comprehensive understanding on the use of flavonoids as αA and αG inhibitors for controlling diabetes.
Keywords: Diabetes; flavonoids; α-amylase inhibitors; α-glucosidase inhibitors.