Characterization of α-Glucosidase Inhibitors from Clinacanthus nutans Lindau Leaves by Gas Chromatography-Mass Spectrometry-Based Metabolomics and Molecular Docking Simulation
Hesham El-Seedi
Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden; [email protected]
Khozirah Saari
Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43300, Selangor Darul Ehsan, Malaysia; [email protected] (F.A.); [email protected] (K.S.)
Faridah Abas
Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43300, Selangor Darul Ehsan, Malaysia; [email protected] (F.A.); [email protected] (K.S.)
Vikneswari Perumal
Faculty Pharmacy & Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh 30450, Perak Darul Ridzuan, Malaysia; [email protected]
α-glucosidase inhibitors, Clinacanthus nutans, diabetes, GC-MS, partial least square
Abstract
Background: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the α-glucosidase inhibitory activity of C. nutans leaves extracts, and to identify the metabolites responsible for the bioactivity. Methods: Crude extract obtained from the dried leaves using 80% methanolic solution was further partitioned using different polarity solvents. The resultant extracts were investigated for their α-glucosidase inhibitory potential followed by metabolites profiling using the gas chromatography tandem with mass spectrometry (GC-MS). Results: Multivariate data analysis was developed by correlating the bioactivity, and GC-MS data generated a suitable partial least square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid, phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular docking was carried out using the crystal structure Saccharomyces cerevisiae isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411, and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding. Conclusion: The study provides informative data on the potential α-glucosidase inhibitors identified in C. nutans leaves, indicating the plant’s therapeutic effect to manage hyperglycemia.
Keywords: α-glucosidase inhibitors, Clinacanthus nutans, diabetes, GC-MS, partial least square
Author Biographies
Hesham El-Seedi, Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden; [email protected]
H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43300, Selangor Darul Ehsan, Malaysia; [email protected] (F.A.); [email protected] (K.S.)
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