Abstract
Aberrant platelet activation plays a critical role in the pathogenesis of heart attack and stroke. DL-3-n-butylphthalide (NBP) has been approved in China to treat stroke with multiple mechanisms. The anti-stroke effects of NBP may be related to its antiplatelet effects reported in rats in addition to its antioxidative, antiapoptotic, and angiogenic effects. However, the effects and the underlying mechanisms of NBP on human platelets are not yet clear. In this study, we found that NBP concentration-dependently inhibited human platelet aggregation and ATP release induced by ADP, thrombin, U46619, arachidonic acid, or collagen. NBP also inhibited PAC-1 binding induced by ADP or thrombin and platelet spreading on immobilized fibrinogen. NBP reduced TXA2 synthesis induced by thrombin or collagen via inhibiting cPLA2 phosphorylation, concomitantly with a marked decrease in intracellular calcium mobilization. Moreover, NBP also inhibited human platelet phosphodiesterase (PDE) and elevated 3,5-cyclic adenosine monophosphate level in platelets. In conclusion, NBP significantly inhibits human platelet activation via inhibition of cPLA2-mediated TXA2 synthesis and PDE, and may be effective as an antiplatelet drug to treat other arterial t...Continue Reading
References
Jul 15, 1990·The Biochemical Journal·J E MerrittK E Moores
Jan 5, 2002·Blood·Jianguo JinSatya P Kunapuli
Jan 5, 2002·Methods in Enzymology·Catherine H Berlot
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·M J ChoT K Gartner
Sep 27, 2003·Thrombosis Research·Manuel LabiósJusto Aznar
May 15, 2004·Blood·Haripriya ShankarSatya P Kunapuli
May 29, 2004·Journal of Cardiovascular Pharmacology·Ying PengXiaoliang Wang
Jun 19, 2004·Blood·Sanford J Shattil, Peter J Newman
Mar 11, 2006·The Journal of Pharmacology and Experimental Therapeutics·Yi ZhangXiao-Liang Wang
Jul 22, 2006·Blood·Haripriya ShankarSatya P Kunapuli
Apr 10, 2008·Blood·Xiaoyu SuXiaodong Xi
Nov 6, 2008·Journal of Thrombosis and Haemostasis : JTH·Zhongren DingSatya P Kunapuli
Jun 16, 2009·Brain Research·Song-Jie LiaoRu-Xun Huang
Aug 5, 2009·Thrombosis and Haemostasis·Lisa K Jennings
Jun 18, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ying PengCynthia A Lemere
Aug 31, 2010·Brain Research·Jimei LiLing Wei
Sep 2, 2010·Thrombosis and Haemostasis·Si ZhangZhongren Ding
Nov 13, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Zhenyu LiXiaoping Du
Jun 28, 2011·International Journal of Cancer. Journal International Du Cancer·Chang NiuQinong Ye
Jun 28, 2011·Organic & Biomolecular Chemistry·Xuliang WangYihua Zhang
Sep 29, 2011·Thrombosis and Haemostasis·Liang HuZhongren Ding
Oct 19, 2011·The Journal of Clinical Investigation·Wai Ho TangJohn Hwa
Dec 6, 2011·Journal of Thrombosis and Haemostasis : JTH·A Smolenski
Jan 17, 2012·Neurochemical Research·Lihong ZhangDavid T Yew
Jan 31, 2012·Journal of Cardiovascular Pharmacology·Xi-Lin LuJing-Song Ou
Mar 6, 2012·Neuropharmacology·Jing XuZhuo Yang
Jul 21, 2012·PloS One·ChangE PanZhongren Ding
Nov 13, 2012·Journal of Thrombosis and Haemostasis : JTH·S ZhangZ Ding
Jul 11, 2013·JAMA : the Journal of the American Medical Association·Emmanouil S BrilakisSubhash Banerjee
Jul 31, 2013·Lancet·Gregg W StoneUNKNOWN ADAPT-DES Investigators
Citations
Apr 27, 2018·Cell Biology International·Peng ZhangCuiying Wu
Feb 17, 2019·Journal of Neurosurgery·Zongze LiYuanli Zhao
May 21, 2019·Chinese Medical Journal·Xi-Qian ChenWei Lu
Jun 22, 2020·Aging·Zhou ZengZhiping Hu
Nov 15, 2019·Brain and Behavior·Xiao-Lei ZhangFeng-Yun Hu
Aug 12, 2017·Frontiers in Aging Neuroscience·Zhilin XiongLi'an Huang
Jun 18, 2019·Chinese Medical Journal·Xi-Qian ChenWei Lu
Apr 2, 2021·Oxidative Medicine and Cellular Longevity·Ting ZhuXiaobo Sun
May 25, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ting ZhuXiao-Bo Sun
Aug 8, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Yan HanYong-Hua Zhao
Aug 11, 2021·Neurochemical Research·Chunlin ChenZhifeng Fu
Nov 20, 2021·Medicine·Le YangYankun Chen