In silico Analysis of the Biflavonoids as Novel Inhibitors of α-Glucosidase

Abstract

The inhibition of carbohydrate digestion is an effective strategy to treat diabetes mellitus and its complications. In recent years, natural products, especially the monoflavonoids, have been widely reported to be beneficial in the prevention of diabetes through delaying starch digestion. However, the value of the biflavonoids, another important class of natural compounds, with potential inhibitory effects against carbohydrate-hydrolyzing enzymes, has not yet been elucidated. Therefore, in this paper, we investigated the inhibitory effects of the biflavonoids using an in silico screening method. The docking results showed that the inhibitory effects of the biflavonoids on α-glucosidase from three different sources were different. Taiwaniaflavone-bacteria α-glucosidase complex (−9.37 kcal/mol), taiwaniaflavone-human α-glucosidase complex (−9.69 kcal/mol) and hinokiflavone-Saccharomyces cerevisiae α-glucosidase complex (−10.79 kcal/mol) had the lowest binding energies compared with the other biflavonoids, apigenin and acarbose. These compounds formed a considerable number of hydrogen bonds and hydrophobic interactions with active site residues of the various α-glucosidase, leading to structural changes and inhibition of enzyme activity. The online evaluation of absorption, distribution, metabolism, excretion and toxicity (ADMET) parameters proved that all biflavonoids had better pharmacokinetic properties and lower toxicity. This study suggested that hinokiflavone and taiwaniaflavone could be used as effective α-glucosidase inhibitors, which will help to develop more potent drugs to regulate the postprandial hyperglycemia.

Keywords:

• ADMET (absorption
• biflavonoids
• diabetes mellitus
• distribution
• excretion and toxicity)
• metabolism
• molecular docking
• α-glucosidase

Acknowledgements

The authors are very grateful to the School of Life Sciences, Faculty of Medicine, Tianjin University for providing infrastructure facilities.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (21506152), the Open Fund of Key Laboratory of Biotechnology and Bioresources Utilization (Dalian Minzu University), Ministry of Education (KF2023006), China, the Foundation of State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University (CMEMR2022-B02).