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

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

Compound Danshen dripping pill / Platelet aggregation / Meta-analysis / Network pharmacology / Integrated study

Declarations

Not applicable.

Authors' contributions

Bo Pang, Haofan Xu: Writing-original draft, Statistical analysis. Zhouyi Xie: Methodology. Yi Chen, Mengying Zhang: Data collection and collation. Yu Wei, Qian Zhao: Conceptualization, Formal analysis. Wenjia Wang: Supervision. Jingbo Zhai, Yunhui Hu: Writing - review & editing, Funding acquisition, Project administration.

Ethics approval and consent to participate

The animal studies were granted by the Ethics Committee of Nankai University (Tianjin, China; Approval number: 2023-SYDWLL-000638) and the studies were performed in compliance with the Guide for the Care and Use of Laboratory Animals (Publications No. 8023, revised 1978) published by the National Institutes of Health (NIH).

Consent for publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This research was funded by Tianjin Natural Science Foundation, grand number: 22JCYBJC00180.

Declarations of Competing Interests

Bo Pang, Yu Wei, Mengying Zhang, Qian Zhao, Wenjia Wang and Yunhui Hu are employed by Tianjin Tasly Digital Intelligence Chinese Medicine Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

Acknowledgements

Not applicable.

Authors' other information

Not applicable.

Appendix A. Supporting information

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.prmedi.2025.100062.

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