Frontiers in Pharmacology (Jun 2017)

Specific Combination of Salvianolic Acids As Core Active Ingredients of Danhong Injection for Treatment of Arterial Thrombosis and Its Derived Dry Gangrene

  • Tiechan Zhao,
  • Tiechan Zhao,
  • Lianying Chang,
  • Lianying Chang,
  • Boyong Zhang,
  • Boyong Zhang,
  • Ming Lu,
  • Ming Lu,
  • Xiaoyi Wang,
  • Xiaoyi Wang,
  • John O. Orgah,
  • John O. Orgah,
  • Yuefei Wang,
  • Yuefei Wang,
  • Xiaoxuan Tian,
  • Xiaoxuan Tian,
  • Jing Yang,
  • Jing Yang,
  • Guanwei Fan,
  • Guanwei Fan,
  • Boli Zhang,
  • Boli Zhang,
  • Yan Zhu,
  • Yan Zhu,
  • Yan Zhu

DOI
https://doi.org/10.3389/fphar.2017.00361
Journal volume & issue
Vol. 8

Abstract

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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.

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