BACKGROUND & AIMS:
:Diabetes is associated with vascular complications, such as impaired wound healing and accelerated vascular growth. The different clinical manifestations, such as retinopathy and nephropathy, reveal the severity of enhanced vascular growth known as angiogenesis. This study was performed to evaluate the effects of an extract of Ishige okamurae (IO) and its constituent, Ishophloroglucin A (IPA) on high glucose-induced angiogenesis. A transgenic zebrafish (flk:EGFP) embryo model was used to evaluate vessel growth. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), gap closure, transwell, and Matrigel® assays were used to analyze the proliferation, migration, and capillary formation of EA.hy926 cells. Moreover, protein expression were determined using western blotting. IO extract and IPA suppressed vessel formation in the transgenic zebrafish (flk:EGFP) embryo. IPA attenuated cell proliferation, cell migration, and capillary-like structure formation in high glucose-treated human vascular endothelial cells. Further, IPA down regulated the expression of high glucose-induced vascular endothelial growth factor receptor 2 (VEGFR-2) and downstream signaling molecule cascade. Overall, the IO extract and IPA exhibited anti-angiogenic effects against high glucose-induced angiogenesis, suggesting their potential for use as therapeutic agents in diabetes-related angiogenesis.
背景与目标:
: 糖尿病与血管并发症有关,如伤口愈合受损和血管生长加速。不同的临床表现,如视网膜病变和肾病,揭示了血管生长增强的严重程度,即血管生成。进行这项研究是为了评估石原 (IO) 提取物及其成分Ishophloroglucin A (IPA) 对高糖诱导的血管生成的影响。使用转基因斑马鱼 (flk:EGFP) 胚胎模型评估血管生长。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物 (MTT),间隙闭合,tranwell和Matrigel®测定用于分析EA.hy926细胞的增殖,迁移和毛细血管形成。此外,使用蛋白质印迹法测定蛋白质表达。IO提取物和IPA抑制了转基因斑马鱼 (flk:EGFP) 胚胎中的血管形成。IPA减弱了高糖处理的人血管内皮细胞的细胞增殖,细胞迁移和毛细血管样结构的形成。此外,IPA下调高糖诱导的血管内皮生长因子受体2 (VEGFR-2) 和下游信号分子级联的表达。总体而言,IO提取物和IPA对高糖诱导的血管生成表现出抗血管生成作用,表明它们有潜力用作糖尿病相关血管生成的治疗剂。