Oyewusi, Habeebat Adekilekun and Wu, Yuan Seng * and Safi, Sher Zaman and Roswanira, Abdul Wahab and Mohd Hayrie, Mohd Hatta and Kalaivani, Batumalaie (2023) Molecular dynamics simulations reveal the inhibitory mechanism of Withanolide A against α-glucosidase and α-amylase. Journal of Biomolecular Structure and Dynamics, 41 (13). ISSN 1538-0254
Full text not available from this repository. (Request a copy)Abstract
Diabetes mellitus (DM) is a global chronic disease characterized by hyperglycemia and insulin resistance. The unsavory severe gastrointestinal side-effects of synthetic drugs to regulate hyperglycemia have warranted the search for alternative treatments to inhibit the carbohydrate digestive enzymes (e.g. α-amylase and α-glucosidase). Certain phytochemicals recently captured the scientific community's attention as carbohydrate digestive enzyme inhibitors due to their low toxicity and high efficacy, specifically the Withanolides-loaded extract of Withania somnifera. That said, the present study evaluated in silico the efficacy of Withanolide A in targeting both α-amylase and α-glucosidase in comparison to the synthetic drug Acarbose. Protein-ligand interactions, binding affinity, and stability were characterized using pharmacological profiling, high-end molecular docking, and molecular-dynamic simulation. Withanolide A inhibited the activity of α-glucosidase and α-amylase better, exhibiting good pharmacokinetic properties, absorption, and metabolism. Also, Withanolide A was minimally toxic, with higher bioavailability. Interestingly, Withanolide A bonded well to the active site of α-amylase and α-glucosidase, yielding the lowest binding free energy of -82.144 ± 10.671 kcal/mol and -102.1043 ± 11.231 kcal/mol compared to the Acarbose-enzyme complexes (-63.220 ± 13.283 kcal/mol and -82.148 ± 10.671 kcal/mol). Hence, the findings supported the therapeutic potential of Withanolide A as α-amylase and α-glucosidase inhibitor for DM treatment.Communicated by Ramaswamy H. Sarma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | diabetes; MD simulation; Withanolide A; α-amylase; α-glucosidase. |
| Subjects: | Q Science > QP Physiology R Medicine > RA Public aspects of medicine R Medicine > RC Internal medicine |
| Divisions: | Others > Non Sunway Academics Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020] > Sunway Microbiome Centre [formerly Centre for Virus and Vaccine Research until 2023] |
| Depositing User: | Ms Yong Yee Chan |
| Related URLs: | |
| Date Deposited: | 25 Jul 2024 01:44 |
| Last Modified: | 25 Jul 2024 01:44 |
| URI: | http://eprints.sunway.edu.my/id/eprint/2881 |
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