A Defined Combination of Four Active Principles From the Danhong Injection Is Necessary and Sufficient to Accelerate EPC-Mediated Vascular Repair and Local Angiogenesis
A Defined Combination of Four Active Principles From the Danhong Injection Is Necessary and Sufficient to Accelerate EPC-Mediated Vascular Repair and Local Angiogenesis
复制标题
丹红注射液四种有效成分的明确组合对于加速 EPC 介导的血管修复和局部血管生成是必要且充分的
DOI：
10.3389/fphar.2019.01080
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发表时间：
2018-09-23
影响因子：
5.6
通讯作者：
Gao, Xiumei
中科院分区：
文献类型：
--
作者：
He, Shuang;Guo, Hao;Gao, Xiumei
包括丹红注射液（DHI）在内的中药复方中的许多化合物具有刺激血管生成和促进血管修复的作用，但其化学基础和作用机制尚不清楚。本研究的目的是确定DHI的促血管生成活性的最小天然化学组成，并评估其从局部内皮细胞（EC）和骨髓来源的内皮祖细胞（EPCs）的贡献。我们的研究表明，DHI加速缺血大鼠模型后肢血流恢复的作用归因于其在成熟内皮细胞中的局部CXCR 4介导的促血管生成活性，以及其通过整合激活SDF-1 α/CXCR 4、VEGF/KDR和eNOS/MMP-9信号通路促进EPCs增殖、迁移、粘附和血管生成的能力。组合实验将血管生成活性缩小到DHI中的几个组分中。重构实验确定丹参素、原儿茶醛、丹参素酸B和丹参素酸C以其天然比例的组合对于DHI的血管生成活性是必要和充分的。与完全DHI相比，最小重组四种活性成分在体外促进管腔形成、改善缺血肢体的灌注和恢复以及在体内促进缺血小鼠后肢缺血后的血管生成方面具有相同的效果。
Many compounds in Chinese medicine formulae, including Danhong injection (DHI) formulae, are capable of stimulating angiogenesis and promoting vascular repair, but their chemical basis and action mechanisms remain poorly defined. The aim of this study is to determine the minimal native chemical composition of DHI for the pro-angiogenesis activity and to evaluate its contribution from local endothelial cells (ECs) and bone marrow-derived endothelial progenitor cells (EPCs). Our study demonstrated that the action of DHI in accelerating the recovery of hindlimb blood flow in a ischemic rat model was attributable to its local CXCR4-mediated pro-angiogenesis activity in mature endothelial cells, as well as to its ability to promote the proliferation, migration, adhesion, and angiogenesis of EPCs via integrated activation of SDF-1 alpha/CXCR4, VEGF/KDR, and eNOS/MMP-9 signal pathways. Combination experiments narrowed down the angiogenic activity into a few components in DHI. Reconstitution experiment defined that a combination of tanshinol, protocatechuic aldehyde, salvianolic acid B, and salvianolic acid C in their native proportion was necessary and sufficient for DHI's angiogenic activity. Compared with the full DHI, the minimal reconstituted four active principles had the same effects in promoting tube formation in vitro, improving perfusion and recovery of ischemic limb, and enhancing angiogenesis in ischemic mice post-hindlimb ischemia in vivo.