Aspirin eugenol ester inhibits agonist-induced platelet aggregation in vitro by regulating PI3K/Akt, MAPK and Sirt 1/CD40L pathways.

Abstract

Aspirin eugenol ester (AEE) was a promising drug candidate for treating inflammation, pain and fever and preventing cardiovascular diseases with fewer side effects than its precursors. Previous researches indicated that AEE could markedly inhibit agonist-induced platelet aggregation in vitro and ex vivo, however, the anti-platelet aggregation mechanisms of AEE remain to be defined. Here, AEE in vitro effects on agonist-induced granule-secretion, intercellular Ca2+ mobilization and thromboxane A2 (TXA2) generation were examined. Vasodilator-stimulated phosphoprotein (VASP), mitogen-activated protein kinase (MAPK), Akt, Sirt 1 and CD40L expressions were also studied. In agonist-activated platelets in vitro, AEE markedly attenuated granule secretion markers (P-selectin expression and ATP release), intercellular Ca2+ mobilization and thromboxane B2 (TXB2) formation. AEE also attenuated CD40L activation, suppressed extracellular-signal-regulated protein kinase 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1) and Akt phosphorylation, and recovered Sirt1 expression, but the activation of p38, VASPSer157 and VASPSer239, and the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were not affected by AEE. Overall, this study demonstrates that AEE inhibits agonist-induced platelet aggregation in vitro by regulating PI3K/Akt, MAPK and Sirt 1/CD40L pathways.

• Authors: Dong-Shuai Shen, Ya-Jun Yang, Xiao-Jun Kong, Ning Ma, Xi-Wang Liu, Shi-Hong Li, Zeng-Hua Jiao, Zhe Qin, Mei-Zhou Huang, Jian-Yong Li
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 852 Pg. 1-13 (Jun 05 2019) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 30797789 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Cell Adhesion Molecules
• Microfilament Proteins
• Phosphoproteins
• aspirin eugenol ester
• vasodilator-stimulated phosphoprotein
• CD40 Ligand
• Eugenol
• Thromboxane A2
• Cyclic AMP
• L-Lactate Dehydrogenase
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Caspase 3
• Sirtuin 1
• Cyclic GMP
• Aspirin
• Calcium

Topics

• Animals
• Aspirin (analogs & derivatives, pharmacology)
• CD40 Ligand (metabolism)
• Calcium (metabolism)
• Caspase 3 (metabolism)
• Cell Adhesion Molecules (metabolism)
• Cyclic AMP (metabolism)
• Cyclic GMP (metabolism)
• Eugenol (analogs & derivatives, pharmacology)
• Gene Expression Regulation (drug effects)
• Intracellular Space (drug effects, metabolism)
• L-Lactate Dehydrogenase (metabolism)
• MAP Kinase Signaling System (drug effects)
• Male
• Microfilament Proteins (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoproteins (metabolism)
• Phosphorylation (drug effects)
• Platelet Aggregation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Wistar
• Sirtuin 1 (metabolism)
• Thromboxane A2 (biosynthesis)