Licochalcone a prevents platelet activation and thrombus formation through the inhibition of PLCγ2-PKC, Akt, and MAPK pathways

Li Ming Lien, Kuan Hung Lin, Li Ting Huang, Mei Fang Tseng, Hou Chang Chiu, Ray Jade Chen, Wan Jung Lu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Platelet activation is involved in cardiovascular diseases, such as atherosclerosis and ischemic stroke. Licochalcone A (LA), an active ingredient of licorice, exhibits multiple biological activities such as anti-oxidation and anti-inflammation. However, its role in platelet activation remains unclear. Therefore, the study investigated the antiplatelet mechanism of LA. Our data revealed that LA (2–10 µM) concentration dependently inhibited platelet aggregation induced by collagen, but not thrombin and U46619. LA markedly attenuated collagen-stimulated ATP release, P-selectin secretion, calcium mobilization, and GPIIbIIIa activation, but did not interfere with the collagen binding to platelets. Moreover, LA significantly reduced the activation of PLCγ2, PKC, Akt and MAPKs. Thus, LA attenuates platelet activation, possibly by inhibiting collagen receptor downstream signaling but not by blocking the collagen receptors. In addition, LA prevented adenosine diphosphate (ADP)-induced acute pulmonary thrombosis, fluorescein sodium-induced platelet thrombus formation, and middle cerebral artery occlusion/reperfusion-induced brain injury in mice, but did not affect normal hemostasis. This study demonstrated that LA effectively reduced platelet activation and thrombus formation, in part, through the inhibition of PLCγ2–PKC, Akt, and MAPK pathways, without the side effect of bleeding. These findings also indicate that LA may provide a safe and alternative therapeutic approach for preventing thromboembolic disorders such as stroke.

Original languageEnglish
Article number1500
JournalInternational Journal of Molecular Sciences
Volume18
Issue number7
DOIs
Publication statusPublished - Jul 12 2017

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Keywords

  • Licochalcone A
  • Middle cerebral artery occlusion
  • Platelet activation
  • PLCγ2-PKC
  • Thrombus formation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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