Polyphasic approaches to identify and understand α-glucosidase inhibitory potential of secondary metabolites of Withania coagulans fruit – PubMed Black Hawk Supplements

Abstract

Withania coagulans (WC) is used in traditional and Ayurveda medicine to treat various ailments, including diabetes. Our investigation found that WC fruit hexane extract effectively suppresses α-glucosidase activity (IC₅₀ = 0.013 mg/ml, K_i = 0.012 mg/ml). The purified molecule has an IC₅₀ of 0.004 mg/ml and K_i of 0.0037 mg/ml. FTIR examination indicates distinctive peaks at 3500, 2900, 1770, and 1500 cm^-1 corresponding to functional groups OH bending, CH stretching, CO stretching, and CO stretching. GCMS analysis reveals plant secondary metabolites (PSM) such as n-hexadecenoic acid and methyl 9,10-octadecadienoate. NMR confirms the existence of olefinic fatty acids. The bioactive fraction recorded a non-competitive mode of inhibition of α-glucosidase activity. The cytotoxicity exhibited against HELA cell was IC₅₀ 0.4 mg/ml and found positive in inhibiting the growth of Bacillus cereus, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa. Additionally, ensemble docking and molecular dynamic simulation showed that, out of the four PSMs examined, methyl 12,13-tetradecadienoate interacted with the α-glucosidase enzyme’s allosteric site (BE -128.78 kJ/mol) and changed the configurations of the catalytic sites, as demonstrated by the enzyme’s decreased affinity for isomaltose. The study found that PSMs from WC fruit may inhibit α-glucosidase, making them viable candidates for antidiabetic medication development.

Keywords: Binding energy; Chromatography; Molecular dynamics simulation; Non-competitive inhibition; Plant secondary metabolites; α-Glucosidase inhibitor.

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.