Laser Department, National Institute for Laser, Plasma and Radiation Physics, 077125 Maurele, Romania.
Earth, Environmental and Life Sciences Section, Research Institute of the University of Bucharest, University of Bucharest, 1 B. P. Hașdeu St., 50567 Bucharest, Romania.
Biomolecules. 2021 Nov 14;11(11):1692. doi: 10.3390/biom11111692.
Diabetes represents a major health problem, involving a severe imbalance of blood sugar levels, which can disturb the nerves, eyes, kidneys, and other organs. Diabes management involves several synthetic drugs focused on improving insulin sensitivity, increasing insulin production, and decreasing blood glucose levels, but with unclear molecular mechanisms and severe side effects. Natural chemicals extracted from several plants such as or have aroused great interest for their anti-diabetes activity, but also their hypolipidemic and anti-obesity activity. Here, we focused on the anti-diabetic activity of a few natural and synthetic compounds, in correlation with their pharmacokinetic/pharmacodynamic profiles, especially with their blood-brain barrier (BBB) permeability. We reviewed studies that used bioinformatics methods such as predicted BBB, molecular docking, molecular dynamics and quantitative structure-activity relationship (QSAR) to elucidate the proper action mechanisms of antidiabetic compounds. Currently, it is evident that BBB damage plays a significant role in diabetes disorders, but the molecular mechanisms are not clear. Here, we presented the efficacy of natural (gymnemic acids, quercetin, resveratrol) and synthetic (TAK-242, propofol, or APX3330) compounds in reducing diabetes symptoms and improving BBB dysfunctions. Bioinformatics tools can be helpful in the quest for chemical compounds with effective anti-diabetic activity that can enhance the druggability of molecular targets and provide a deeper understanding of diabetes mechanisms.
糖尿病是一个主要的健康问题，涉及血糖水平的严重失衡，这会干扰神经、眼睛、肾脏和其他器官。糖尿病的治疗涉及几种合成药物，这些药物主要集中在提高胰岛素敏感性、增加胰岛素分泌和降低血糖水平上，但作用机制不明确，副作用严重。从几种植物中提取的天然化学物质，如 或 ，因其抗糖尿病活性，以及降血脂和抗肥胖活性，引起了极大的兴趣。在这里，我们关注了几种天然和合成化合物的抗糖尿病活性，以及它们的药代动力学/药效学特征，特别是它们的血脑屏障（BBB）通透性。我们回顾了使用生物信息学方法的研究，如预测 BBB、分子对接、分子动力学和定量构效关系（QSAR），以阐明抗糖尿病化合物的适当作用机制。目前，很明显，BBB 损伤在糖尿病疾病中起着重要作用，但分子机制尚不清楚。在这里，我们介绍了天然（匙羹藤酸、槲皮素、白藜芦醇）和合成（TAK-242、丙泊酚、或 APX3330）化合物在减轻糖尿病症状和改善 BBB 功能障碍方面的功效。生物信息学工具可以帮助寻找具有有效抗糖尿病活性的化学化合物，从而增强分子靶点的可药性，并深入了解糖尿病的机制。
