Zhang Ling, Yang Yingxin, Wang Yi, Gao Xiumei
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Pharmazie. 2011 Feb;66(2):144-50.
Astragalus membranaceus extract (AME) is a widely used herbal product for the treatment of cardiovascular diseases in China. The present study aimed to evaluate the cardiac protective effects of AME, and to probe the underlying molecular mechanism related to angiogenesis. In this study, AME with 75 microg/mL significantly increased proliferation, migration and tube formation on human umbilical vein endothelial cells (HUVECs). Moreover, in vivo experiments on rats with ligation of left anterior descending artery were performed to study the cardiac protective and angiogenic effect of AME (50 and 100 mg/kg i.g. for 3, 7, 14 days). The results showed that AME inhibited cardiac fibrosis, reduced infarct size, and increased capillary and arteriole densities. Meanwhile, western blot was used to determine protein levels of VEGF, p-AKT, p-GSK3beta and p-mTOR. AME significantly elevated protein expression of VEGF and increased phosphorylation of AKT, GSK3beta and mTOR. In conclusion, AME exerted cardiac protective and angiogenic effects in the ischemic injured heart. The activation of AKT/GSK3beta and AKT/mTOR pathways and elevated expression of VEGF may contribute to the promoted neovascularisation by AME.
黄芪提取物(AME)在中国是一种广泛用于治疗心血管疾病的草药产品。本研究旨在评估AME的心脏保护作用,并探究其与血管生成相关的潜在分子机制。在本研究中,75微克/毫升的AME显著增加了人脐静脉内皮细胞(HUVECs)的增殖、迁移和管腔形成。此外,对左冠状动脉前降支结扎的大鼠进行了体内实验,以研究AME(50和100毫克/千克,灌胃,持续3、7、14天)的心脏保护和血管生成作用。结果表明,AME抑制心脏纤维化,减小梗死面积,并增加毛细血管和小动脉密度。同时,采用蛋白质印迹法测定VEGF、p-AKT、p-GSK3β和p-mTOR的蛋白水平。AME显著提高VEGF的蛋白表达,并增加AKT、GSK3β和mTOR的磷酸化水平。总之,AME对缺血损伤心脏具有心脏保护和血管生成作用。AKT/GSK3β和AKT/mTOR信号通路的激活以及VEGF表达的升高可能是AME促进新生血管形成的原因。