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对α-葡萄糖苷酶、二肽基肽酶(IV)的抑制作用评估以及与2型糖尿病相关的分子对接抗糖尿病研究。

Inhibitory evaluation of on α-glucosidase, DPP (IV) and studies in antidiabetic with molecular docking relevance to type 2 diabetes mellitus.

作者信息

Zabidi Nur Athirah, Ishak Nur Akmal, Hamid Muhajir, Ashari Siti Efliza, Mohammad Latif Muhammad Alif

机构信息

Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

Centre of Foundation Studies for Agricultural Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

出版信息

J Enzyme Inhib Med Chem. 2021 Dec;36(1):109-121. doi: 10.1080/14756366.2020.1844680.

Abstract

The inhibition of α-glucosidase and DPP enzymes capable of effectively reducing blood glucose level in the management of type 2 diabetes. The purpose of the present study is to evaluate the inhibitory potential of α-glucosidase and DPP (IV) activity including with the NBDG uptake assay and insulin secretion activities through studies. The selected of active compounds obtained from the screening of compounds by LC-MS were docked with the targeted enzyme that involved in the mechanism of T2DM. From the results, root extracts displayed a better promising outcome in α-glucosidase (IC 2.72 ± 0.32) as compared with the fruit extracts (IC 3.87 ± 0.32). Besides, root extracts also displayed a better activity in the inhibition of DPP (IV), enhance insulin secretion and glucose uptake activity. Molecular docking results revealing that phlorizin binds strongly with α-glucosidase, DPP (IV) and Insulin receptor (IR) enzymes with achieving the lowest binding energy value. The present work suggests several of the compounds have the potential that contribute towards inhibiting α-glucosidase and DPP (IV) and thus effective in lowering post-prandial hyperglycaemia.

摘要

抑制α-葡萄糖苷酶和二肽基肽酶(DPP)能够在2型糖尿病的管理中有效降低血糖水平。本研究的目的是通过研究评估α-葡萄糖苷酶和DPP(IV)活性的抑制潜力,包括采用2-脱氧-D-葡萄糖(NBDG)摄取试验和胰岛素分泌活性。通过液相色谱-质谱联用(LC-MS)筛选化合物获得的活性化合物与参与2型糖尿病发病机制的靶向酶进行对接。结果显示,与果实提取物(IC50 3.87±0.32)相比,根提取物在α-葡萄糖苷酶抑制方面表现出更好的前景(IC50 2.72±0.32)。此外,根提取物在抑制DPP(IV)、增强胰岛素分泌和葡萄糖摄取活性方面也表现出更好的活性。分子对接结果表明,根皮苷与α-葡萄糖苷酶、DPP(IV)和胰岛素受体(IR)酶紧密结合,达到最低结合能值。目前的研究表明,几种化合物具有抑制α-葡萄糖苷酶和DPP(IV)的潜力,因此对降低餐后高血糖有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3432/7717572/9af79ffbeeee/IENZ_A_1844680_F0001_B.jpg

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