Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmadabad, Gujarat, 382 481, India.
King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Curr Gene Ther. 2020;20(3):223-235. doi: 10.2174/1566523220999200726225457.
Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications.
The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes.
In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity.
In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate.
In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.
餐后高血糖被认为是脑血管并发症的一个主要危险因素。
本研究旨在通过保护易发生中风的 2 型糖尿病患者，从体外到体内研究阐明伏格列波糖的有益作用，改善餐后血糖状态。
借助 iGEMDOCK+Pymol+docking 软件和蛋白质药物数据库（PDB）进行了计算机分子对接和虚拟筛选。根据对接研究的结果，进行了体内研究以确定可能的神经保护作用。通过单次静脉注射链脲佐菌素（90mg/kg）诱导 T2DM 新生大鼠。诱导后 6 周，给予伏格列波糖 10mg/kg 灌胃，持续 2 周。8 周后，糖尿病大鼠接受大脑中动脉闭塞，术后 72 小时确定神经功能缺损。采集血液以测定血清葡萄糖、CK-MB、LDH 和脂质水平。切除大脑以测定脑梗死体积、大脑半脑重量差、Na+-K+ATP 酶活性、ROS 参数、NO 水平和醛糖还原酶活性。
计算机对接研究显示，与中风相关的蛋白质具有良好的对接结合评分，这可能假设了伏格列波糖在中风中的神经保护作用。在本体内研究中，伏格列波糖预处理显示血清葡萄糖和脂质水平显著降低（p<0.05）。伏格列波糖可显著降低神经评分（p<0.05）、脑梗死体积、大脑半脑重量差异。在生化评估中，伏格列波糖治疗可使血液中的 CK-MB、LDH 和 NO 水平显著降低（p<0.05），并降低脑匀浆中的 Na+-K+ATP 酶、氧化应激和醛糖还原酶活性。
计算机分子对接和虚拟筛选研究以及 MCAo 诱导中风的体内研究结果支持伏格列波糖具有强大的抗中风特征，可能具有神经保护治疗作用。
