In-silico screening and identification of phytochemicals from Centella asiatica as potential inhibitors of sodium-glucose co-transporter 2 for treating diabetes
Sodium-glucose co-transporter 2 (SGLT-2) is a major transport protein responsible for reabsorption of glucose from the kidney back to the bloodstream. Inhibiting this protein effectively lowers the glucose level of diabetic patients; however, the use of synthetic SGLT-2 inhibitors has been linked to some serious adverse effects. There is a need to identify safer alternatives that are equally or more effective as the current inhibitor drugs. Phytochemicals are known for their efficacy as herbal remedies, but these molecules remain underexplored as source of therapeutic agents. In this study, we performed in silico screening to identify potential SGLT-2 inhibitors from the 21 phytochemicals from Centella asiatica. Docking results identified eleven compounds with estimated binding energies comparable to that of known inhibitors drugs. The stability of the complexes was then elucidated using 100 ns MD simulations. From our dynamic binding free energy calculations using MM/PBSA, asiaticoside, betulinic acid, centellasapogenol, methyl brahmate, and rutin exceeded at least one of the binding energies of the reference compounds, which highlights their strong affinity towards SGLT-2. Among the five, betulinic acid, centellasapogenol, and methyl brahmate maintained their structural stability to the same extent as the references and exhibited better oral bioavailability and excellent drug-like properties. Because of these results, it is recommended to prioritize betulinic acid, centellasapogenol, and methyl brahmate in future in vitro and in vivo studies to verify their potential as inhibitor drugs for diabetes therapies. Communicated by Ramaswamy H. Sarma.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Journal of biomolecular structure & dynamics - 40(2022), 22 vom: 29., Seite 12221-12238 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Macalalad, Mark Andrian B [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.12.2022 Date Revised 23.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/07391102.2021.1969282 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a In-silico screening and identification of phytochemicals from Centella asiatica as potential inhibitors of sodium-glucose co-transporter 2 for treating diabetes |
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| 520 | |a Sodium-glucose co-transporter 2 (SGLT-2) is a major transport protein responsible for reabsorption of glucose from the kidney back to the bloodstream. Inhibiting this protein effectively lowers the glucose level of diabetic patients; however, the use of synthetic SGLT-2 inhibitors has been linked to some serious adverse effects. There is a need to identify safer alternatives that are equally or more effective as the current inhibitor drugs. Phytochemicals are known for their efficacy as herbal remedies, but these molecules remain underexplored as source of therapeutic agents. In this study, we performed in silico screening to identify potential SGLT-2 inhibitors from the 21 phytochemicals from Centella asiatica. Docking results identified eleven compounds with estimated binding energies comparable to that of known inhibitors drugs. The stability of the complexes was then elucidated using 100 ns MD simulations. From our dynamic binding free energy calculations using MM/PBSA, asiaticoside, betulinic acid, centellasapogenol, methyl brahmate, and rutin exceeded at least one of the binding energies of the reference compounds, which highlights their strong affinity towards SGLT-2. Among the five, betulinic acid, centellasapogenol, and methyl brahmate maintained their structural stability to the same extent as the references and exhibited better oral bioavailability and excellent drug-like properties. Because of these results, it is recommended to prioritize betulinic acid, centellasapogenol, and methyl brahmate in future in vitro and in vivo studies to verify their potential as inhibitor drugs for diabetes therapies. Communicated by Ramaswamy H. Sarma | ||
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