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 α-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 α-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 α-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 α-glucosidase. The IC50 values from the α-glucosidase inhibitory assay ranged between 16 and 275 µg/ml. Overall, E60 displayed significantly higher α-glucosidase inhibition activity, while E0 showed the lowest α-glucosidase inhibition activity. Major compounds detected in S. zalacca fruits were sugars, fatty acids, and sterols, including myo-inositol, palmitic acid, stearic acid, and β-sitosterol. Moreover, the results obtained from molecular docking indicated that palmitic acid and β-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 α-glucosidase inhibitory activity. The hydrophobic compounds, including palmitic acid and β-sitosterol, were found to induce the α-glucosidase inhibition activity.
Highlights
Diabetes mellitus (DM) is a chronic metabolic disorder that may lead to other macro- and microvascular complications
World populations majorly practice conventional medicines relying on plantbased medicines due to the availability [2]
Various plants have been utilized as a traditional remedy for multiples diseases and conditions for centuries [3]. e effect and mechanism of most plants for the treatment of diabetes can be related to their inhibitory activities against α-glucosidase enzyme. is intestinal enzyme is found in the brush border of the small intestine, responsible for catalysing the breakdown of polysaccharides into monosaccharides, reducing the postprandial glucose level, thereby decreasing the hyperglycaemia in DM patients [4]
Summary
Diabetes mellitus (DM) is a chronic metabolic disorder that may lead to other macro- and microvascular complications.e highest number of DM cases that have been reported to date was recorded in Asian countries, which cover about 60% of the world’s DM patients [1]. E effect and mechanism of most plants for the treatment of diabetes can be related to their inhibitory activities against α-glucosidase enzyme. Salaaca zalacca is one example of a plant that is traditionally used as a hypoglycemic remedy, more commonly popular in Asian countries, including Malaysia, Myanmar, Indonesia, and ailand [8, 9]. S. zalacca possesses antioxidant, anticancer, and antidiabetic effects [11,12,13,14], attributable to their high levels of vitamin C, Phenolics acids, and flavonoids [10]. Erefore, this study intends to initially analyse the α-glucosidase (EC 3.2.1.20, α-D-glucoside glucohydrolase) inhibitory activity of the S. zalacca fruit extracts. It is one of the pathways involved in the management of DM. One of the most appropriate methods to analyse these constituents are by using the metabolomics approach
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