In-silico and in-vitro hybrid approach to identify glucagon-like peptide-1 receptor agonists from anti-diabetic natural products. Issue 10 (19th May 2023)

• Record Type: Journal Article
• Authors: Chatterjee, Debanjan; Vhora, Nazmina; Goswami, Ashutosh; Hiray, Aishwarya; Jain, Alok; Kate, Abhijeet S.
• Is Part Of: Natural product research. Volume 37:Issue 10(2023)
• Page Start: 1651
• Page End: 1655
• Publication Date: 2023-05-19
• Subjects: alpha-mangostin -- glucagon-like peptide-1 receptor -- MD simulation -- molecular docking -- insulin secretion assay; Natural products -- Periodicals; Natural products -- Research -- Periodicals; Biological Factors -- Periodicals; Biological Products -- Periodicals; 547
• DOI: 10.1080/14786419.2022.2106567
• Languages: English
• ISSNs: 1478-6419

Abstract

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: UF0001