2. Academic Validation
  3. Eugenol Suppresses Platelet Activation and Mitigates Pulmonary Thromboembolism in Humans and Murine Models

Eugenol Suppresses Platelet Activation and Mitigates Pulmonary Thromboembolism in Humans and Murine Models

  • Int J Mol Sci. 2024 Feb 8;25(4):2098. doi: 10.3390/ijms25042098.
Wei-Chieh Huang 1,  Lan-Hsin Shu 2,  Yu-Ju Kuo 1,  Kevin Shu-Leung Lai 3,  Chih-Wei Hsia 4,  Ting-Lin Yen 5,  Chih-Hsuan Hsia 6,  Thanasekaran Jayakumar 7,  Chih-Hao Yang 8,  Joen-Rong Sheu 1 8
Affiliations

Affiliations

  • 1 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
  • 2 Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei 106, Taiwan.
  • 3 Division of Critical Care Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan.
  • 4 Department of Medical Research, Taipei Medical University Hospital, Taipei 110, Taiwan.
  • 5 Department of Medical Research, Cathay General Hospital, Taipei 106, Taiwan.
  • 6 Translational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 111, Taiwan.
  • 7 Department of Ecology and Environmental Sciences, Pondicherry University, Puducherry 605014, India.
  • 8 Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
PMID: 38396774 DOI: 10.3390/ijms25042098
Abstract

Platelets assume a pivotal role in the pathogenesis of cardiovascular diseases (CVDs), emphasizing their significance in disease progression. Consequently, addressing CVDs necessitates a targeted approach focused on mitigating platelet activation. Eugenol, predominantly derived from clove oil, is recognized for its Antibacterial, Anticancer, and anti-inflammatory properties, rendering it a valuable medicinal agent. This investigation delves into the intricate mechanisms through which eugenol influences human platelets. At a low concentration of 2 μM, eugenol demonstrates inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Notably, Thrombin and U46619 remain unaffected by eugenol. Its modulatory effects extend to ATP release, P-Selectin expression, and intracellular calcium levels ([Ca2+]i). Eugenol significantly inhibits various signaling cascades, including Phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3β, mitogen-activated protein kinases, and cytosolic Phospholipase A2 (cPLA2)/thromboxane A2 (TxA2) formation induced by collagen. Eugenol selectively inhibited cPLA2/TxA2 phosphorylation induced by AA, not affecting p38 MAPK. In ADP-treated mice, eugenol reduced occluded lung vessels by platelet thrombi without extending bleeding time. In conclusion, eugenol exerts a potent inhibitory effect on platelet activation, achieved through the inhibition of the PLCγ2-PKC and cPLA2-TxA2 cascade, consequently suppressing platelet aggregation. These findings underscore the potential therapeutic applications of eugenol in CVDs.

Keywords

MAPK; PI3K/Akt/GSK-3β; PLCγ2–PKC; cPLA2/TxA2; eugenol; human platelets; pulmonary thrombosis.

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