Investigation of the Anti-Diabetic Potential of Coccinia barteri (Hook.F.) Leaf Using in Vitro and in Silico Molecular Docking Approaches

Abstract

Objectives/Background Several plants with various chemical constituents have been widely explored for managing diabetes mellitus. One of the most common strategies is the inhibitors of the α-amylase and α-glucosidase, key regulatory enzymes in diabetes. This study aims to investigate the anti-diabetic activity of methanolic extract of Coccinia barteri leaves using in vitro α-amylase enzyme inhibition assay and in silico molecular docking study. Methods The dried pulverized leaf of Coccinia barteri was extracted by maceration using methanol. Qualitative and quantitative phytochemical analyses of the powdered leaf extract were carried out using standard procedures. The extract was fractionated using n-hexane, ethyl acetate, n-butanol and aqueous methanol. In vitro anti-diabetic study of the different fractions and sub-fractions was investigated by α-Amylase Inhibition Assay. Sub-fractions of the ethyl acetate fraction of C.barteri leaf with the highest in vitro anti-diabetic activity were subjected to GC-MS analysis. The compounds detected by GC-MS were selected as ligands for α-amylase and α-glucosidase in the molecular docking study. Results The phytochemical analysis revealed the presence of saponins, alkaloids, tannins, glycosides, steroids, flavonoids, and cyanide. Compared to the control drug, the ethyl acetate fraction of Coccinia barteri leaf gave a 2-fold lower IC50. GCMS chromatogram of the most active sub-fraction revealed the presence of 18 major compounds. Piperine showed good binding affinity (−6.9 kcal/mol) to α-amylase and displayed hydrogen bonding with ARG 344 and HIS 210, along with pi alkyl bonds with TRP 83, HIS 80, LEU 166, and LEU 232. For α-glucosidase, piperine and 2,4-di-tertbutylphenol surpassed the standard with binding energies of −7.1 kcal/mol and - 6.9 kcal/mol, respectively. Drug likeness and toxicity assessments confirmed adherence to Lipinski's rule, with both compounds showing non-mutagenic and non-tumorigenic properties. Conclusion The ethyl acetate fraction of the Coccinia barteri leaf exhibits potential anti-diabetic activity, which may be attributed to the inhibition of α-amylase and α-glucosidase, by its constituents, piperine and 2,4-di-tertbutylphenol.