Specific Combination of Salvianolic Acids As Core Active Ingredients of Danhong Injection for Treatment of Arterial Thrombosis and Its Derived Dry Gangrene.
Specific Combination of Salvianolic Acids As Core Active Ingredients of Danhong Injection for Treatment of Arterial Thrombosis and Its Derived Dry Gangrene.
复制标题
丹红注射液以丹酚酸为核心活性成分治疗动脉血栓及其衍生干性坏疽的具体组合
DOI：
10.3389/fphar.2017.00361
复制
发表时间：
2017
影响因子：
5.6
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Zhao T;Chang L;Zhang B;Lu M;Wang X;Orgah JO;Wang Y;Tian X;Yang J;Fan G;Zhang B;Zhu Y
虽然单靶点抗血小板药物在临床上应用广泛，但其在耐药性和出血方面的局限性已经开始了联合治疗的趋势。丹红注射液是我国广泛使用的治疗心脑血管疾病的注射剂。然而，其确切的临床疗效和功能成分仍有待探索。本研究探讨了DHI的抗血栓作用及其化学基础。在光化学诱导的血栓形成模型中，DHI有效地溶解血栓并改善其衍生的干性坏疽。DHI抑制多种GPCR激动剂诱导的血小板粘附、聚集和下游Ca2+和cAMP信号通路。对DHI文库进行功能筛选，确定其主要活性成分为7个丹参酮酸。丹参素A和C的组合在体外协同抑制血小板聚集，而丹参素B拮抗这种作用。我们的研究揭示了DHI的抗血栓形成活性。DHI的多靶点机制证明了天然抗血栓联合治疗的有效性。丹参素酸作为DHI的核心抗血栓活性的鉴定以及它们的不同组合可以协同或拮抗地为更安全的临床应用提供更好的指导，并为DHI的进一步开发铺平了道路。
Although single-targeting anti-platelet agents are used extensively in clinics, their limitations in resistance and bleeding have started a trend of combination therapy. Danhong injection (DHI) is a widely prescribed injection medicine for cardiovascular and cerebrovascular diseases in China. However, its precise clinical efficacy and functional components remain unexplored. In this study, we investigated the anti-thrombotic role and its chemical basis of DHI. In a photochemically-induced thrombosis model, DHI effectively dissolved thrombus and ameliorated its derived dry gangrene. DHI inhibited multiple GPCR agonists-induced platelet adhesion, aggregation and downstream Ca2+ and cAMP signaling pathways. A functional screen of DHI library identified its major active components as a cluster of seven salvianolic acids. A combination of salvianolic acid A and C synergistically inhibited platelet aggregation in vitro while salvianolic acid B antagonized this effect. Our study revealed the anti-thrombotic activity of DHI. The multi-targeting mechanism of DHI proves the effectiveness of a natural anti-thrombotic combination therapy. The identification of salvianolic acids as a core anti-thrombotic activity of DHI and the discovery that their different combinations could either synergistically or antagonistically provide a better guidance for safer clinical application and paves the way for further development of DHI.