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

Abstract

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.

Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics

“…Subsequent in vitro and in vivo studies have confirmed that Sal-A inhibits ADP and collagen-induced platelet aggregation and arterial thrombus formation in mice [121][122][123][124] . Salvianolic acids, in particular Sal-A and Sal-C, are core components of Danhong injection exerting anti-thrombotic activity [125] . The cardiovascular actions of salvianolic acids have recently been comprehensively reviewed elsewhere [126] .…”

Salvianolic acids from antithrombotic Traditional Chinese Medicine Danshen are antagonists of human P2Y1 and P2Y12 receptors

“…Thus, the results suggest that colloidal aggregation is not a major contributor to the inhibition of the specific binding of [ 3 H]2MeSADP by salvianolic acids. Additionally, the reports that SAA and SAC are more potent at ADP-induced than at thrombin-induced platelet aggregation 8 , 35 may also support a specific effect of these compounds.…”

Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study

“…Analysis of the components in the Dan-Hong injection and their pharmacodynamic effects has revealed that DSS, SAA, SAB, and HSYA are the main active ingredients [30,46,[49][50][51]. Therefore, a pharmacokinetic study of the these four active ingredients appeared to be reasonable and necessary.…”