Antiplatelet activity of loureirin A by attenuating Akt phosphorylation: In vitro studies

Eur J Pharmacol. 2015 Jan 5:746:63-9. doi: 10.1016/j.ejphar.2014.10.059. Epub 2014 Nov 13.

Abstract

Loureirin A is a flavonoid extracted from Dragon׳s Blood that has been used to promote blood circulation and remove stasis in Chinese traditional medicine. However, the mechanisms of these effects are not fully understood. We explored the anti-platelet activity and underlying mechanism of loureirin A in vitro. Our results indicated that loureirin A negatively affected agonist-induced platelet aggregation such as collagen, collagen-related peptide (CRP), ADP and thrombin. Loureirin A inhibited collagen-induced platelet ATP secretion and thrombin-stimulated P-selectin expression in a dose-dependent manner. Platelet spreading on immobilized fibrinogen was significantly impaired in the presence of loureirin A. Immunoblotting analysis indicated that 100μM of loureirin A almost completely eliminated collagen-induced Akt phosphorylation at Ser473. Interestingly, a submaximal dose (50μM) of loureirin A had an additive inhibitory effect with the phosphoinositide 3-kinase (PI3K) inhibitor Ly294002 on collage-induced Akt phosphorylation in platelets. Taken together, loureirin A had an inhibitory effect on platelet activation, perhaps through an impairment of PI3K/Akt signaling.

Keywords: Aggregation; Loureirin A; PI3K/Akt; Platelet; Spreading.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Blood Platelets / drug effects
  • Blood Platelets / physiology
  • Chalcones / pharmacology*
  • Fibrinogen / chemistry
  • Fibrinogen / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Immobilized Proteins / chemistry
  • Immobilized Proteins / metabolism
  • Male
  • Mice
  • P-Selectin / metabolism
  • Phosphorylation / drug effects
  • Plant Extracts / chemistry
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Thrombin / pharmacology

Substances

  • Chalcones
  • Immobilized Proteins
  • P-Selectin
  • Plant Extracts
  • Platelet Aggregation Inhibitors
  • loureirin A
  • Adenosine Triphosphate
  • Fibrinogen
  • Proto-Oncogene Proteins c-akt
  • Thrombin
  • dragon's blood