Abstract
Cordycepin can effectively inhibit adenosine diphosphate-induced platelet aggregation; however, the inhibitory effect on shear-induced platelet aggregation is not known. Pathological high shear stress is an important factor in inducing platelet aggregation in the human body. In order to further study the antithrombotic effect and mechanism of cordycepin, in this study, a microfluidic chip model was developed that not only can mimic stenotic vessels but also provide high shear stress needed in the experiment. The inhibitory effects of cordycepin on platelet aggregation, activation of P-selectin and glycoprotein IIb/IIIa, phosphatidyl serine exposure, glycoprotein Ib/von Willebrand factor binding, and Akt protein phosphorylation, induced by a pathological high shear rate (10,000 s−1), were studied. In addition, we also investigated the effect of cordycepin on adenosine diphosphate and arachinodic acid-induced platelet aggregation by turbidimetry. The results showed that cordycepin can inhibit platelet aggregation, P-selectin expression, glycoprotein IIb/IIIa activation, phosphatidylserine exposure, and Akt protein phosphorylation induced by a pathological high shear rate. It did not affect the combination of GPIb and vWF because the combination of CD14-staind platelets and CD41-staind platelets by von Willebrand factor was not inhibited by cordycepin. Under static conditions, cordycepin can inhibit adenosine diphosphate and arachinodic acid-induced platelet aggregation.
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The data available on the request to the corresponding author.
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Funding
This work was supported by Graduate Innovation Fund of Yongchuan Hospital affiliated to Chongqing Medical University (YJSCX202204), and Joint Project of Chongqing Health Commission and Science and Technology Bureau (2023GDRC008).
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XG contributed to the study design, data collection, statistical analysis, data interpretation, and manuscript preparation. TZ contributed to data collection. XH contributed to statistical analysis. CH and XH contributed to data collection and statistical analysis. YL contributed to the manuscript preparation. All the authors read and approved the final manuscript.
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Gao, X., Zhang, T., Huang, X. et al. Cordycepin Inhibits Pathological High Shear-Induced Platelet Aggregation, Activation, and Phosphatidylserine Exposure by Regulating the Phosphorylation of Akt Protein. Rev. Bras. Farmacogn. 33, 768–777 (2023). https://doi.org/10.1007/s43450-023-00408-4
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DOI: https://doi.org/10.1007/s43450-023-00408-4