Excessive angiogenesis can be the root cause of many pathological conditions. Various types of ion channels are found on the endothelial cells. These ion channels play a vital role in the multi-stepped process of angiogenesis. The study aims to investigate the anti-angiogenic effects of specific ion channel modulators mefloquine (volume-regulated chloride channel blocker), lubiprostone (ClC-2 channel agonist), and 4-aminopyridine (voltage-gated potassium channel blocker). The anti-angiogenic activity of ion channel modulators was screened by measuring its effects on the area of neovascularization and histopathological studies by in vivo (corneal neovascularization) method and by in vitro assays, endothelial cell proliferation assay, cell migration assay, and matrigel cord-like morphogenesis assay. The test and standard drug (bevacizumab) groups were compared with the control group using one-way ANOVA, followed by post hoc test, and Dunnett’s test to compare the mean of all the groups with the control mean. The results revealed that mefloquine at the dose of 0.6% w/v and 1.0% w/v, lubiprostone at the dose of 0.5% w/v and 1.0% w/v, and 4-aminopyridine at the dose of 2% w/v and 4% w/v showed significant anti-angiogenic property. In the studies on human umbilical vein endothelial cells, the test drugs (100 nM) showed significant inhibition of proliferation, migration, and decrease in network length of cord-like tubes. The scientific findings indicate that the test drugs have potent anti-angiogenic activity by inhibiting the cell proliferation, inhibiting the cell volume increase, arresting the cell cycle progression and by causing membrane hyperpolarization. The potent anti-angiogenic drugs obtained by repurposing these ion channel modulators, in the further studies, will be able to treat the diseases due to excess angiogenesis from the root cause.

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氯离子和钾离子通道调节剂的抗血管生成活性：改变离子通道调节剂的用途

过度的血管生成可能是许多病理状况的根本原因。在内皮细胞上发现了各种类型的离子通道。这些离子通道在血管生成的多步过程中起着至关重要的作用。这项研究旨在研究特定离子通道调节剂甲氟喹（音量调节的氯通道阻滞剂），鲁比前列酮（ClC-2通道激动剂）和4-氨基吡啶（电压门控钾通道阻滞剂）的抗血管生成作用。离子通道调节剂的抗血管生成活性可通过体内（角膜新血管形成）方法，体外测定，内皮细胞增殖测定，细胞迁移测定和基质胶脐带测定来测量其对新血管形成区域和组织病理学研究的影响，从而进行筛选像形态发生测定。用单向方差分析将测试组和标准药物（贝伐单抗）组与对照组进行比较，然后进行事后检验和Dunnett检验，以比较所有组的平均值和对照组的平均值。结果显示，甲氟喹剂量为0.6％w / v和1.0％w / v，鲁比前列酮剂量为0.5％w / v和1.0％w / v，4-氨基吡啶的剂量为2％w / v。 v和4％w / v显示出显着的抗血管生成特性。在对人脐静脉内皮细胞的研究中，受试药物（100 nM）显示出对脐带状管的增殖，迁移和网络长度减少的显着抑制作用。科学发现表明，受试药物通过抑制细胞增殖，抑制细胞体积增加，具有有效的抗血管生成活性，阻止细胞周期进程并引起膜超极化。在进一步的研究中，通过重新利用这些离子通道调节剂获得的有效的抗血管生成药物将能够治疗由于根本原因引起的过度血管生成所致的疾病。