title: Salvianolic acid B inhibits platelets as a P2Y12 antagonist and PDE inhibitor: evidence from clinic to laboratory.
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.
authors: Department of Cardiology, Huashan Hospital, Fudan University.
authors: Lei
authors: L
authors: Liu
authors: Department of Cardiology, Huashan Hospital, Fudan University.
authors: Jian
authors: J
authors: Li
authors: Key Laboratory of Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China.
authors: Yan
authors: Y
authors: Zhang
authors: Key Laboratory of Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China.
authors: Shenghui
authors: S
authors: Zhang
authors: Key Laboratory of Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China.
authors: Jianqin
authors: J
authors: Ye
authors: Department of Cardiology, Huashan Hospital, Fudan University.
authors: Zhichao
authors: Z
authors: Wen
authors: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Jianping
authors: J
authors: Ding
authors: Department of Physiology, and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, USA.
authors: Satya P
authors: SP
authors: Kunapuli
authors: Department of Cardiology, Huashan Hospital, Fudan University. Electronic address: luoxp2007@yahoo.com.cn.
authors: Xinping
authors: X
authors: Luo
authors: Key Laboratory of Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China. Electronic address: dingzr@fudan.edu.cn.
authors: Zhongren
authors: Z
authors: Ding
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy*; D000368:Aged; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D001572:Benzofurans / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D058921:Purinergic P2Y Receptor Antagonists / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D027561:Salvia miltiorrhiza / Q000737:chemistry; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D053630:Depsides
chemical_list: D001241:Aspirin; D001572:Benzofurans; D000077144:Clopidogrel; D004365:Drugs, Chinese Herbal; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013988:Ticlopidine; C076944:salvianolic acid B; D053630:Depsides
keywords: P2Y(12) receptor antagonist; acute coronary syndrome; antiplatelet; phosphodiesterase inhibitor; salvianolate