Flavonoids as dual-target inhibitors against α-glucosidase and α-amylase: a systematic review of in vitro studies

Diabetes mellitus remains a major global health burden and great attention is directed at natural therapeutics. This systematic review aimed to evaluate the potential of flavonoids as antidiabetic agents through their ability to inhibit α-amylase and α-glucosidase, two key starch digestive enzymes. Six scientific databases were queried up until August 21, 2022, for in vitro studies reporting the IC50 results of purified flavonoids on α-amylase or α-glucosidase, along with the respective data of acarbose control. A total of 339 articles were assessed as eligible and subjected to the data extraction process, resulting in 1643 retrieved flavonoid structures. Chemical structures were then rigorously standardized and curated to 974 unique compounds, in which 177 flavonoids showed both inhibitions against α-amylase and α-glucosidase. Quality assessment was conducted following a modified CONSORT checklist. The structure-activity relationships revealed that a double bond C2=C3 and a keto group C4=O is essential for simultaneous inhibition. The hydroxyl group at C3 is favourable for α-glucosidase inhibition but detrimental to the effect against α-amylase. Further notable features which affect α-glucosidase and α-amylase inhibition were also discussed. Several limitations were considered, including the inconsistency among included studies, language restriction, and the contemporaneity of the review. In conclusion, the systematic review has summarized some crucial findings in the investigation of flavonoids as dual-target inhibitors against α-glucosidase and α-amylase and proposed several orientations for future research.