PDF(Pubmed)
Abstract：
Astragaloside IV, a prime active component of Astragalus membranaceus, has potential as a neuroprotectant. We aimed to identify the active ingredients in A. membranaceus and assess if Astragaloside IV can improve cerebral ischemia-reperfusion injury (CIRI) cell apoptosis by reducing P-Src and P-GRK2 via ryanodine receptor (RyR) expression inhibition. We used bioinformatics analysis to examine the effects of A. membranaceus on ischemic stroke. We studied brain samples from middle cerebral artery occlusion (MCAO) mice treated with normal saline, Astragaloside IV, and sham mice for pathology and Western blot tests. We also tested PC12 cells in vitro with or without Astragaloside IV or GSK180736A using Western blotting and fluorescence assays. Our bioinformatics analysis suggested a possible association between A. membranaceus, calcium ion pathways, and apoptosis pathways. Western blot data indicated Astragaloside IV significantly decreased RyR, p-Src, and downstream phosphorylated GRK2, PLC, CaMKII, and IP3R levels in MCAO mice brains. Astragaloside IV also considerably inhibited pro-apoptotic and oxidative stress-associated proteins\' expression while boosting anti-apoptotic protein expression. The results suggest Astragaloside IV can inhibit RyR expression, subsequently reducing brain cell apoptosis.
摘要：
黄芪甲苷,黄芪的主要活性成分，具有作为神经保护剂的潜力。我们的目的是确定膜紫草中的活性成分，并评估黄芪甲苷是否可以通过ryanodine受体（RyR）表达抑制减少P-Src和P-GRK2来改善脑缺血再灌注损伤（CIRI）细胞凋亡。我们使用生物信息学分析来检查A.musinaceus对缺血性中风的影响。我们研究了用生理盐水处理的大脑中动脉阻塞（MCAO）小鼠的脑样本，黄芪甲苷,和假小鼠进行病理学和蛋白质印迹试验。我们还使用Western印迹和荧光测定在有或没有黄芪甲苷IV或GSK180736A的情况下体外测试PC12细胞。我们的生物信息学分析表明，膜虫之间可能存在关联，钙离子途径，和凋亡途径。Westernblot数据显示黄芪甲苷显著降低RyR,p-Src,和下游磷酸化GRK2，PLC，CaMKII,和MCAO小鼠大脑中的IP3R水平。黄芪甲苷还显著抑制促凋亡和氧化应激相关蛋白的表达，同时增强抗凋亡蛋白的表达。结果提示黄芪甲苷能抑制RyR的表达,随后减少脑细胞凋亡。
