Honey and lime juice flavonoids as potential adjunctive remedies against obesity and diabetes mellitus risks via glucagon receptor and glucagon-like peptide-1 receptor binding mechanisms: an in-silico investigation

Abstract

Obesity and diabetes mellitus are closely associated, such that obesity exacerbates the risk of type 2 diabetes. This study investigated the anti-obesity and anti-diabetic effects of honey and lime juice flavonoids, via an in-Silico approach. AutoDock Vina protocols was used for molecular docking whereas UCSF Chimera and Discovery Studio were used to visualize for the mechanism of gallic acid, epigallocatechin, quercetin, naphthoresorcinol, caffeic acid, p. coumarin, sinapic acid, protocatechuic acid, chorogenic acid, and valeric acid interaction with glucagon receptor (GR) and glucagon-like peptide 1 receptor (GLP-1R) implicated in obesity and diabetes pathophysiology. Results showed that the binding affinities of the ligands were higher in GR than in GLP-1R. The binding affinities were gallic acid (−9.9 kcal/mol in pocket A of GR; −7.6 kcal/mol in pocket B of GLP-1R), epigallocatechin (−9.5 kcal/mol in pocket B of GR; −6.8 kcal/mol in pocket A of GLP-1R), quercetin (−9.2 kcal/mol in pocket A of GR; −6.4 kcal/mol in pocket A of GLP-1R), naphthoresorcinol (−7.3 kcal/mol in pocket A of GR; -5.7 kcal/mol in pocket B of GLP-1R), and caffeic acid (−7.1 kcal/mol in pocket A of GR; −5.1 kcal/mol in pocket A of GLP-1R). The 2D visualization showed that interaction of these ligands was possible due to H-bond formation between the amino acid residues in GR and GLP-1R. GR binding pockets ‘ amino acid residues observed were A: Glu-362, Ile-315, Asn-318; B: His-177, Asn-404, Arg-346, Cys-171, and Leu-399. Similarly, GLP-1R binding pockets ‘ amino acid residues observed were A: Glu-76, Asp-74, and Arg-64; B: Glu-68. Based on the druglike properties’ predictions, these honey/lime flavonoids have the potential to be optimized and enlisted for clinical trials towards the discovery of adjunctive chemotherapy for diabetes and obesity management.