Salvianolic acid B inhibits platelets as a P2Y12 antagonist and PDE inhibitor: evidence from clinic to laboratory

Thromb Res. 2014 Oct;134(4):866-76. doi: 10.1016/j.thromres.2014.07.019. Epub 2014 Jul 17.

Abstract

Salviae miltiorrhiza (Danshen) has been used for thousands of years in China and some other Asian countries to treat atherothrombotic diseases. Salvianolate which consists of three water-soluble ingredients purified from Salviae miltiorrhiza, has been approved by Chinese SFDA to treat coronary artery disease. So far, there is no evidence clearly showing the clinical efficiency of salvianolate and the underlying mechanism. This study is to evaluate the effects of salvianolate on platelets in patients with acute coronary syndrome and explore the underlying mechanism. We evaluated the effects of salvianolate on platelets in patients with acute coronary syndrome by measuring ADP-induced PAC-1 binding and P-selectin expression on platelets. Salvianolate significantly potentiated the antiplatelet effects of standard dual antiplatelet therapy. We also investigated the antiplatelet effects of salvianolatic acid B (Sal-B), the major component which composes 85% of salvianolate. Sal-B inhibits human platelet activation induced by multiple agonists in vitro by inhibiting phosphodiesterase (PDE) and antagonizing P2Y12 receptor. For the first time, we show the antiplatelet efficiency of salvianolate in ACS patients undergoing treatment with clopidogrel plus aspirin, and demonstrate that Sal-B, the major component of salvianolate inhibits human platelet activation via PDE inhibition and P2Y12 antagonism which may account for the clinical antiplatelet effects of salvianolate. Our results suggest that Sal-B may substitute salvianolate for clinical use.

Keywords: P2Y(12) receptor antagonist; acute coronary syndrome; antiplatelet; phosphodiesterase inhibitor; salvianolate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / drug therapy*
  • Aged
  • Aspirin / pharmacology
  • Aspirin / therapeutic use
  • Benzofurans / isolation & purification
  • Benzofurans / pharmacology
  • Benzofurans / therapeutic use*
  • Blood Platelets / cytology
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Clopidogrel
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Phosphodiesterase Inhibitors / isolation & purification
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors / isolation & purification
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Purinergic P2Y Receptor Antagonists / isolation & purification
  • Purinergic P2Y Receptor Antagonists / pharmacology
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Salvia miltiorrhiza / chemistry
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use

Substances

  • Benzofurans
  • Drugs, Chinese Herbal
  • Phosphodiesterase Inhibitors
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • salvianolic acid B
  • Ticlopidine
  • Aspirin