Decoding the alpha-amylase inhibitory activity of Garcinia indica Choisy by computational and experimental studies

Abstract

Garcinia indica Choisy is traditionally used to manage diabetes mellitus, also used in various herbal formulations, and is indicated as an insulin sensitizer. The present study investigates the hydroalcoholic extract of G. indica Choisy rind as an α-amylase inhibitor, followed by the identification of the probable lead hits via a computational approach. LC-MS analyse were carried out. In vitro assays for alpha amylase were performed at concentrations of G. indica ranging from (1000–125 µg/mL) and acarbose (25–1.56 µg/mL) with inhibition times ranging from 5th to 30th min. In silico study was performed based upon the bioactives traced from LC-MS data retrieved from the PubChem database and predicted for probable targets of diabetes mellitus, followed by a drug-likeness score, probable side effects, and an ADMET profile. In addition, molecular docking and the dynamics of the representative complex were explored using AutoDock Vina and Gromac. In vitro study revealed IC50 values of 400.5, 526.07, 728.05, 792.7, 848.3, and 897.5 µg/mL and acarbose displayed IC50 values of <1.56, 6.6, 10.46, 12.6, 14.14, and 15.24 µg/mL respectively. LC-MS analysis identified 17 bioactives, of which 13 showed positive druglikness; among them, 5 bioactives were predicted to modulate AMY2A. The gene set enrichment analysis revealed that AMY2A and gambogic acid possessed high edge counts, with the lowest binding energy of gambogic acid- AMY2A (-11.7 kcal/mol), followed by amentoflavone (-10.6 kcal/mol), volkensiflavone (-9.3 kcal/mol), fukugcide (-8.8 kcal/mol), and garcinol (-7.7 kcal/mol) when compared with acarbose- AMY2A (-7.7 kcal/mol), which also indicates high stability up to 100 ns in molecular simulation. Hydroalcoholic extract of G. indica rind α-amylase inhibitory activity, may be due to the presence of gambogic acid and other bioactives. Thus, it can be speculated that G. indica may possess anti-diabetic activity by reducing the post prandial glucose level. This needs to be further confirmed via enriched fractions or pure substances with inhibitory activity to develop Traditional medicine based new drugs