Abstract
Fruit of salak (Salaaca zalacca) is traditionally used and commercialized as an antidiabetic agent. However, scientific evidence to prove this folk claim is quite lacking. Therefore, this research was aimed to evaluate the alpha -glucosidase inhibition activity of S. zalacca fruit and identify the bioactive compounds. The fruits were extracted by different ratios of ethanol and water (0, 20, 40, 60, 80, 100%, v/v) to get E0 (100% water), E20 (20% ethanol), E40 (40% ethanol), E60 (60% ethanol), E80 (80% ethanol), and E100 (100% ethanol) extracts. The extracts obtained were subjected to the alpha -glucosidase inhibitory assay. Gas chromatography-mass spectrometry- (GC-MS-) based metabolomics approach was used in profiling the bioactive metabolites present in the extracts. Orthogonal partial least square (OPLS) was used to correlate GC-MS data and alpha -glucosidase assay results to identify the possible chemical markers. All active compounds identified were subjected to molecular docking. The extracts from the S. zalacca fruit showed potent inhibition activity against alpha -glucosidase. The IC50 values from the alpha -glucosidase inhibitory assay ranged between 16 and 275 mu g/ml. Overall, E60 displayed significantly higher alpha -glucosidase inhibition activity, while E0 showed the lowest alpha -glucosidase inhibition activity. Major compounds detected in S. zalacca fruits were sugars, fatty acids, and sterols, including myo-inositol, palmitic acid, stearic acid, and beta -sitosterol. Moreover, the results obtained from molecular docking indicated that palmitic acid and beta -sitosterol were close to the active side of the enzyme. Some of the residues that interacted include HID295, ASN259, LEU313, LYS125, PHE159, VAL216, PHE178, TYR72, TYR158, HIE315, ARG315, and PHE303. The bioassay result strongly suggests that E60 extract from S. zalacca fruits has potential alpha -glucosidase inhibitory activity. The hydrophobic compounds, including palmitic acid and beta -sitosterol, were found to induce the alpha -glucosidase inhibition activity.