Quek, Alexandra and Kassim, Nur Kartinee and Lim, Pei Cee and Tan, Dai Chuan and Mohammad Latif, Muhammad Alif and Ismail, Amin and Shaari, Khozirah and Awang, Khalijah (2021) Alpha-Amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory effects of Melicope latifolia bark extracts and identification of bioactive constituents using in vitro and in silico approaches. Pharmaceutical Biology, 59 (1). pp. 964-973. ISSN 1388-0209, DOI https://doi.org/10.1080/13880209.2021.1948065.
Full text not available from this repository.Abstract
Context Melicope latifolia (DC.) T. G. Hartley (Rutaceae) was reported to contain various phytochemicals including coumarins, flavonoids, and acetophenones. Objective This study investigates the antidiabetic and antioxidant effects of M. latifolia bark extracts, fractions, and isolated constituents. Materials and methods Melicope latifolia extracts (hexane, chloroform, and methanol), fractions, and isolated constituents with varying concentrations (0.078-10 mg/mL) were subjected to in vitro alpha-amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory assay. Molecular docking was performed to study the binding mechanism of active compounds towards alpha-amylase and DPP-4 enzymes. The antioxidant activity of M. latifolia fractions and compounds were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and beta-carotene bleaching assays. Results Melicope latifolia chloroform extract showed the highest antidiabetic activity (alpha-amylase IC50: 1464.32 mu g/mL; DPP-4 IC50: 221.58 mu g/mL). Fractionation of chloroform extract yielded four major fractions (CF1-CF4) whereby CF3 showed the highest antidiabetic activity (alpha-amylase IC50: 397.68 mu g/mL; DPP-4 IC50: 37.16 mu g/mL) and resulted in beta-sitosterol (1), halfordin (2), methyl p-coumarate (3), and protocatechuic acid (4). Isolation of compounds 2-4 from the species and their DPP-4 inhibitory were reported for the first time. Compound 2 showed the highest alpha-amylase (IC50: 197.53 mu M) and beta-carotene (88.48%) inhibition, and formed the highest number of molecular interactions with critical amino acid residues of alpha-amylase. The highest DPP-4 inhibition was exhibited by compound 3 (IC50: 911.44 mu M). Discussion and conclusions The in vitro and in silico analyses indicated the potential of M. latifolia as an alternative source of alpha-amylase and DPP-4 inhibitors. Further pharmacological studies on the compounds are recommended.
| Item Type: | Article |
|---|---|
| Funders: | Malaysia Ministry of Higher Education (MOHE) Fundamental Research Grant Scheme[FRGS/1/2019/WAB11/UPM/02/1] |
| Uncontrolled Keywords: | Diabetes;Antidiabetic;Molecular docking;Antioxidant |
| Subjects: | Q Science > QD Chemistry |
| Divisions: | Faculty of Science |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 20 Jul 2022 07:20 |
| Last Modified: | 20 Jul 2022 07:20 |
| URI: | http://eprints.um.edu.my/id/eprint/33965 |
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