دورية أكاديمية
Identification of flavonoid C-glycosides as promising antidiabetics targeting protein tyrosine phosphatase 1B
| العنوان: | Identification of flavonoid C-glycosides as promising antidiabetics targeting protein tyrosine phosphatase 1B |
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| المؤلفون: | Rampadarath, Athika, Balogun, Fatai Oladunni, Pillay, Charlene, Sabiu, Saheed |
| بيانات النشر: | Hindawi Limited |
| سنة النشر: | 2024 |
| المجموعة: | DUT Open Scholar (Durban University of Technology) |
| مصطلحات موضوعية: | 1116 Medical Physiology, Humans, Diabetes Mellitus, Type 2, Flavonoids, Glycosides, Enzyme Inhibitors, Hypoglycemic Agents, Protein Tyrosine Phosphatase, Non-Receptor Type 1 |
| الوصف: | Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of the insulin signaling pathway, has gained attention as a validated druggable target in the management of type 2 diabetes mellitus (T2DM). The lack of clinically approved PTP1B inhibitors has continued to prompt research in plant-derived therapeutics possibly due to their relatively lesser toxicity profiles. Flavonoid C-glycosides are one of the plant-derived metabolites gaining increased relevance as antidiabetic agents, but their possible mechanism of action remains largely unknown. This study investigates the antidiabetic potential of flavonoid C-glycosides against PTP1B in silico and in vitro . Of the seven flavonoid C-glycosides docked against the enzyme, three compounds (apigenin, vitexin, and orientin) had the best affinity for the enzyme with a binding score of -7.3 kcal/mol each, relative to -7.4 kcal/mol for the reference standard, ursolic acid. A further probe (in terms of stability, flexibility, and compactness) of the complexes over a molecular dynamics time study of 100 ns for the three compounds suggested orientin as the most outstanding inhibitor of PTP1B owing to its overall -34.47 kcal/mol binding energy score compared to ursolic acid (-19.24 kcal/mol). This observation was in accordance with the in vitro evaluation result, where orientin had a half maximal inhibitory concentration (IC 50 ) of 0.18 mg/ml relative to 0.13 mg/ml for the reference standard. The kinetics of inhibition of PTP1B by orientin was mixed-type with V max and K m values of 0.004 μ M/s and 0.515 μ M. Put together, the results suggest orientin as a potential PTP1B inhibitor and could therefore be further explored in the management T2DM as a promising therapeutic agent. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 11 p; Electronic-eCollection |
| اللغة: | English |
| تدمد: | 2314-6745 |
| العلاقة: | Journal of Diabetes Research; Vol. 2022; Rampadarath, A. et al. 2022. Identification of flavonoid C-glycosides as promising antidiabetics targeting protein tyrosine phosphatase 1B. Journal of Diabetes Research: 6233217-. doi:10.1155/2022/6233217; 2314-6753 (Online); isidoc: 2R1YR; pubmed: 35782627; https://hdl.handle.net/10321/5148Test |
| DOI: | 10.1155/2022/6233217 |
| الإتاحة: | https://doi.org/10.1155/2022/6233217Test https://hdl.handle.net/10321/5148Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.23DA9CB |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 23146745 |
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| DOI: | 10.1155/2022/6233217 |