YiqiHuoxue Decoction and Its Ethanol Precipitation Show Anti-Platelet and Antithrombotic Effects by Suppressing Thromboxane B2 Formation.

Background YiqiHuoxue decoction (YHD) is frequently prescribed to prevent and treat cardiovascular diseases. YHD inhibits platelet aggregation, however the underlying mechanisms are unclear. Methods The in vitro and in vivo anti-platelet and antithrombotic effects of YHD and ethanol-precipitated YHD (EYHD) and underlying mechanisms were investigated. Forty-six Sprague-Dawley (SD) rats and 36 male Kunming mice were examined. Ten SD rats were used to assess the cytotoxicity of YHD and EYHD by releasing lactate dehydrogenase from treated platelets. The remaining 36 SD rats were divided into six groups (six per group), including control saline (5 mL/kg), aspirin (20 mg/kg), YHD low dosage (0.2 g/kg), YHD high dosage (2.0 g/kg), 75% EYHD low dosage (0.2 g/kg), and 75% EYHD high dosage (2.0 g/kg) groups to detect platelet aggregation; the 36 Kunming mice were divided into 6 groups to detect mesenteric arterial thrombosis induction. Thromboxane B2 (TXB2) levels were determined by enzyme immunoassay. Results YHD high dosage and 75% EYHD (low and high dosage) inhibited ADP-induced platelet aggregation. Moreover, collagen-induced platelet aggregation was significantly suppressed by YHD (high dosage), 75% EYHD (high dosage), and 75% EYHD (low dose). Rats given 75% EYHD (high dose) displayed a marked reduction in collagen-induced platelet aggregation at 2 h post-administration. YHD and EYHD markedly prolonged the onset of thrombosis causing loose attachment of the thrombus to the vascular endothelium, but bleeding and clotting times were not significantly changed. Finally, YHD and EYHD markedly reduced TXB2 levels. Conclusions YHD and EYHD effectively inhibit platelet activation and thrombosis, presumably by suppressing TXB2.

[1]  B. Açar,et al.  Predictors of Impaired Reperfusion after Percutaneous Coronary Intervention in Patients with In-Hospital Acute Stent Thrombosis: A Retrospective Analyses of 5 Years of Data. , 2017, Acta Cardiologica Sinica.

[2]  Ping Li,et al.  Shen-Yuan-Dan Capsule Inhibiting Inflammatory Reaction by Regulating Insulin Receptor Substrate 1/PI3K/Akt/NF-κB Signaling Pathway in Apoliprotein E Knockout Mice Fed with a High-Fat Diet. , 2017, Acta Cardiologica Sinica.

[3]  W. Kang,et al.  Antithrombotic Effect and Mechanism of Radix Paeoniae Rubra , 2017, BioMed research international.

[4]  C. Hassan,et al.  Gastrointestinal endoscopy in patients on anticoagulant therapy and antiplatelet agents , 2016, Annals of gastroenterology.

[5]  B. Nieswandt,et al.  Proplatelet formation is selectively inhibited by collagen type I through Syk-independent GPVI signaling , 2016, Journal of Cell Science.

[6]  Shu-Wha Lin,et al.  A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models , 2016, Thrombosis and Haemostasis.

[7]  G. Lemesle,et al.  Effect of aspirin in addition to oral anticoagulants in stable coronary artery disease outpatients with an indication for anticoagulation. , 2016, Panminerva medica.

[8]  Qihua Zhu,et al.  Design, synthesis and antithrombotic evaluation of novel dabigatran etexilate analogs, a new series of non-peptides thrombin inhibitors. , 2015, Bioorganic & medicinal chemistry.

[9]  A. Ferro,et al.  Antiplatelet drug resistance: Molecular insights and clinical implications. , 2015, Prostaglandins & other lipid mediators.

[10]  G. Montalescot,et al.  Dual antiplatelet therapy: optimal timing, management, and duration. , 2015, European heart journal. Cardiovascular pharmacotherapy.

[11]  D. Fitzmaurice,et al.  The prognostic utility of tests of platelet function for the detection of 'aspirin resistance' in patients with established cardiovascular or cerebrovascular disease: a systematic review and economic evaluation. , 2015, Health technology assessment.

[12]  Miaoyu Wang,et al.  Characterization and Antihyperglycemic Activity of a Polysaccharide from Dioscorea opposita Thunb Roots , 2015, International journal of molecular sciences.

[13]  I. Mrdović,et al.  Impact of platelet phenotype on myocardial infarction , 2015, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[14]  Jie Tang,et al.  Platelet Inhibition Agents: Current and Future P2Y12 Receptor Antagonists. , 2014, Current vascular pharmacology.

[15]  Wang Peil Effect of Supplementing Qi and Activating Blood Circulation Chinese Herbs on the Syndrome of Qi Deficiency and Blood Stasis Syndrome in Patients with Acute Coronary Syndrome after Intervention Therapy , 2015 .

[16]  P. Metharom,et al.  Role of Focal Adhesion Tyrosine Kinases in GPVI-Dependent Platelet Activation and Reactive Oxygen Species Formation , 2014, PloS one.

[17]  Junfeng Fan,et al.  Alditols and monosaccharides from sorghum vinegar can attenuate platelet aggregation by inhibiting cyclooxygenase-1 and thromboxane-A2 synthase. , 2014, Journal of ethnopharmacology.

[18]  Guiqing Yu,et al.  Biomedical mechanisms of blood stasis syndrome of coronary heart disease by systems biology approaches , 2014, Chinese Journal of Integrative Medicine.

[19]  S. M. Kamruzzaman,et al.  Ginsenoside‐Rp1 inhibits platelet activation and thrombus formation via impaired glycoprotein VI signalling pathway, tyrosine phosphorylation and MAPK activation , 2012, British journal of pharmacology.

[20]  Wang Shao-li Quality of life of Chinese herbal medicine for nourishing Qi and removing blood stasis on acute coronary syndrome patients after percutaneous coronary intervention , 2012 .

[21]  Hui Zhang,et al.  The effects of Buyang Huanwu Decoction on hemorheological disorders and energy metabolism in rats with coronary heart disease. , 2011, Journal of ethnopharmacology.

[22]  M. Freund,et al.  Mechanisms underlying FeCl3‐induced arterial thrombosis , 2011, Journal of thrombosis and haemostasis : JTH.

[23]  Ning-sheng Wang,et al.  Antithrombotic effects of Danggui, Honghua and potential drug interaction with clopidogrel. , 2010, Journal of ethnopharmacology.

[24]  L. Jennings Mechanisms of platelet activation: Need for new strategies to protect against platelet-mediated atherothrombosis , 2009, Thrombosis and Haemostasis.

[25]  Hang Li-hua Effects of "Yiqi Huoxue Decoction" on Serum PC III, TNF-α and ET-1 in Rats After Myocardial Infarction with Left Ventricular Remodeling , 2004 .