Anti-platelet aggregation effect of Compound Danshen dripping pill: An integrated study of meta-analysis, network pharmacology, and in vivo and vitro experiments

Compound Danshen Dripping Pill (CDDP) is a marketed Chinese patent medicine, primarily efficacious in “promoting blood circulation to remove blood stasis, regulating Qi to relieve pain”. CDDP, as an anti-platelet aggregation drug, has been applied in clinic. However, the evidence has not been critically assessed, and the underlying mechanism has still not been fully understood. A meta-analysis was conducted to collect randomized controlled trials (RCTs) from PubMed, Embase, Cochrane library, Web of Science, CNKI, Wanfang and VIP, and assess the efficacy and safety of CDDP against platelet aggregation. A network pharmacology analysis was performed to predict the potential mechanisms of CDDP against platelet aggregation. A series of in vitro and vivo experiments were conducted to reveal the potential mechanisms of CDDP against platelet aggregation. The pooled result of the meta-analysis involving 20 RCTs showed a more significant reduction in platelet aggregation rate after CDDP plus anti-platelet drugs treatment than anti-platelet drugs alone (SMD=1.27, 95 % CI: 0.97–1.57, P < 0.0001). The network pharmacology analysis found 86 overlapping target genes between CDDP and platelet aggregation that were closely related to lipid, atherosclerosis and inflammation signal pathways. The in vitro and vivo experiments found that CDDP inhibited carrageenan-induced thrombi in tissue vessels of mice. Especially, the combination of CDDP and aspirin/clopidogrel showed a better effect of inhibiting thrombus. CDDP also decreased the level of serum P-selectin and TXB2, and the expression of tumor necrosis factor α, P-selectin and activated matrix metalloproteinase 2 in tissues. CDDP protected human umbilical vein endothelial cells (HUVECs) against lipopolysaccharide (LPS)-induced cell death and reduced the expression of tumor necrosis factor-like cytokine 1 A and vascular endothelial growth factor-α. Meanwhile, CDDP reduced the adhesion of ox-LDL-induced platelets and LPS-induced THP-1 monocytes to HUVECs, and inhibited thrombin-induced human platelet clotting. This integrated study suggests that CDDP have a potential anti-platelet aggregation effect. It may provide a new option for anti-platelet aggregation in clinical practice.