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Tetramethylpyrazine Inhibits Platelet Adhesion and Inflammatory Response in Vascular Endothelial Cells by Inhibiting P38 MAPK and NF-κB Signaling Pathways

  • Han Zhang
  • Weiwei Tang
  • Shuang Wang
  • Junhua Zhang
  • Xiang FanEmail author
Original Article


Damaged vascular endothelial cells after ischemic stroke release inflammatory cytokines and adhesion molecules, which could trigger platelet adhesion to vascular endothelial cells and platelet activation, and accelerate thrombus formation. Tetramethylpyrazine is the main bioactive component of Chuanxiong, which has demonstrated considerable protective effects in cerebrovascular diseases. However, the effect and mechanisms of tetramethylpyrazine on platelet adhesion to ischemia/reperfusion-injured endothelial cells have not been elucidated. In this study, we established an oxygen-glucose deprivation/reoxygenation (OGD/R)–induced brain microvascular endothelial cells (BMECs) injury model to investigate the protective effects of tetramethylpyrazine on platelet adhesion to endothelial cells and potential mechanisms. Experimental results showed that tetramethylpyrazine inhibited platelets adhesion to BMECs, alleviated expression of inflammatory cytokines and adhesion molecules on BMECs, and protected BMECs injured by OGD/R. Furthermore, tetramethylpyrazine could inhibit P38 MAPK and NF-κB activation in injured BMECs by OGD/R and inhibition of P38 MAPK with SB303580 and NF-κB with Bay-11-7082 attenuated the reduction of platelets adhesion to BMECs by tetramethylpyrazine. In conclusion, tetramethylpyrazine protected BMECs and inhibited platelets adhesion to BMECs after OGD/R injury, which was partially mediated by inhibiting P38 MAPK and NF-κB signaling pathways.


tetramethylpyrazine platelet adhesion inflammation NF-κB ischemia/reperfusion brain microvascular endothelial cells 



serine/threonine kinase 1


BCL2-associated X


B cell lymphoma-2


brain microvascular endothelial cells


Cell Counting Kit-8


C-X-C motif chemokine receptor 4


C-X-C motif chemokine receptor 7


Dulbecco’s Modified Eagle’s Medium


Earle’s Balanced Salts


extracellular regulated MAP kinase


fetal bovine serum


glyceraldehyde-3-phosphate dehydrogenase


hypoxia inducible factor 1 subunit alpha


high mobility group box 1


heme oxygenase 1


intercellular adhesion molecule-1


interleukin 1 beta


interleukin 6


interleukin 8


lactate dehydrogenase




mitogen-activated protein kinase


macrophage cationic peptide 1


mixed lineage kinase domain-like protein


nuclear factor-kappa B


nuclear factor, erythroid 2 like 2


oxygen-glucose deprivation/reoxygenation


phosphate-buffered saline


prostaglandin E1


receptor-interacting protein kinase 1


receptor-interacting protein kinase 3


piperazine-1,4-bis(2-ethanesulfonic acid)


stromal cell-derived factor 1


toll-like receptor 4


tumor necrosis factor alpha


vascular cell adhesion molecule 1


Author Contributions

HZ and XF contributed to the design of the study. HZ, WT, and SW were responsible for the data collection. HZ, WT, and XF analyzed the data. HZ and XF interpreted the data. XF drafted the manuscript. JZ revised the manuscript content. All the authors read and approved the final manuscript.

Funding information

This research was funded by National Natural Science Foundation of China (81622051) and Natural Science Foundation of Tianjin City (15JCYBJC54800).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Tianjin State Key Laboratory of Modern Chinese MedicineTianjin University of Traditional Chinese MedicineTianjinChina
  2. 2.Institute of Traditional Chinese MedicineTianjin University of Traditional Chinese MedicineTianjinChina

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