Murugan Ramadurai, Tamil Selvan Silambarasan, Dharmalingam Jothinathan Mukesh Kumar, Srinivasan Guru Prasad, Rajan Renuka Remya, Prasad Monisha
Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, IND.
Cureus. 2024 Feb 7;16(2):e53810. doi: 10.7759/cureus.53810. eCollection 2024 Feb.
Aim By using molecular docking analysis (MDA) to examine its interactions with important regulatory proteins linked to diabetes, such as glycogen synthase kinase 3 beta (GSK3β), insulin receptor (IR), and glucose kinase (GCK), this study seeks to explore the therapeutic potential of myricetin, a naturally occurring flavonoid. Objective The main goal is to determine potential effects on insulin signalling, GSK3β activity, and glucose metabolism by evaluating the binding affinities of myricetin with GCK, IR, and GSK3β through MDA. In order to assess the drug affinity of myricetin, the study also intends to perform absorption, distribution, metabolism, and excretion (ADME) studies. Materials and methods To model the interaction between myricetin and the target proteins (GCK, IR, and GSK3β), we used molecular docking analysis with computational tools. ADME studies were also included in the study to evaluate drug affinity. Identification of binding sites, essential residues, and interaction stability were all part of the structural analysis. Results As evidence of possible interactions with these regulatory proteins, myricetin showed positive binding affinities with GCK, IR, and GSK3β. Strong interactions with important ligand recognition residues were seen in the docking into IR, indicating a potential impact on insulin signalling. Moreover, a strong binding affinity for GCK indicated potential effects on the metabolism of glucose. Studies using ADME confirmed the high drug affinity of myricetin. Conclusion This work sheds light on the multi-target potential of myricetin in the regulation of diabetes. It appears that it has the ability to influence glucose metabolism, suppress GSK3β activity, and regulate insulin signalling based on its interactions with IR, GSK3β, and GCK. Although these computational results show promise, more experimental work is necessary to confirm and fully understand the precise mechanisms that underlie myricetin's effects on the regulation of diabetes.
目的 通过使用分子对接分析（MDA）来研究杨梅素（一种天然存在的类黄酮）与糖尿病相关重要调节蛋白（如糖原合酶激酶3β（GSK3β）、胰岛素受体（IR）和葡萄糖激酶（GCK））的相互作用，本研究旨在探索杨梅素的治疗潜力。
目的 主要目标是通过MDA评估杨梅素与GCK、IR和GSK3β的结合亲和力，从而确定其对胰岛素信号传导、GSK3β活性和葡萄糖代谢的潜在影响。为了评估杨梅素的药物亲和力，该研究还打算进行吸收、分布、代谢和排泄（ADME）研究。
材料和方法 为了模拟杨梅素与靶蛋白（GCK、IR和GSK3β）之间的相互作用，我们使用了计算工具进行分子对接分析。该研究还包括ADME研究以评估药物亲和力。结合位点、关键残基和相互作用稳定性的鉴定均属于结构分析的一部分。
结果 作为与这些调节蛋白可能相互作用的证据，杨梅素与GCK、IR和GSK3β表现出正结合亲和力。在对接至IR时观察到与重要配体识别残基的强烈相互作用，表明对胰岛素信号传导有潜在影响。此外，对GCK的强结合亲和力表明对葡萄糖代谢有潜在影响。使用ADME进行的研究证实了杨梅素具有高药物亲和力。
结论 这项工作揭示了杨梅素在糖尿病调节中的多靶点潜力。基于其与IR、GSK3β和GCK的相互作用，它似乎有能力影响葡萄糖代谢、抑制GSK3β活性并调节胰岛素信号传导。尽管这些计算结果显示出前景，但仍需要更多的实验工作来证实并充分理解杨梅素对糖尿病调节作用的精确机制。
