Although single-targeting anti-platelet agents are used extensively in clinics, their limitations in resistance and bleeding have started a trend zelda r33 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 buderim glace ginger 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.