In-silico and in-vitro hybrid approach to identify glucagon-like peptide-1 receptor agonists from anti-diabetic natural products

Abstract

Natural products have contributed immensely towards the treatment of various diseases including diabetes. Here, a database of small molecules from nature possessing antidiabetic properties was analysed and shortlisted according to their structural diversity. Later, those structures were screened by in-silico docking studies to understand their affinity towards glucagon-like peptide-1 (GLP-1) receptor. The selected molecules were isolated and investigated further by integrated in-vitro and in-silico approaches. Alpha-mangostin was found to be suitable due to its excellent docking score and isolation yield. A pancreatic beta cell line was used to test the activity of alpha-mangostin and observed a 3-fold increase in insulin secretion compared to 15 mM glucose control. Further, in-silico molecular dynamics simulations studies have validated its target by showing conformational changes at the functionally active part of the GLP-1 receptor. This screening strategy can be applied to identify pertinent natural products rapidly for various therapeutic targets.

Graphical Abstract

Keywords:

• alpha-mangostin
• glucagon-like peptide-1 receptor
• MD simulation
• molecular docking
• insulin secretion assay

Acknowledgements

The authors are thankful to NIPER-Ahmedabad for providing the necessary facilities. AJ acknowledges the Department of Biotechnology, Govt of India for the Ramalingaswami Re-entry Fellowship-2019.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.