title: Panax quinquefolium saponin combined with dual antiplatelet drugs inhibits platelet adhesion to injured HUVECs via PI3K/AKT and COX pathways.
abstract: BACKGROUND
  Panax quinquefolium saponin (PQS) is the active component extracted from traditional Chinese medicine Panax quinquefolius L. and has been widely used as a supplement to dual antiplatelet drugs (DA) for treatment of coronary artery disease (CAD) for two decades; however, the efficacy of PQS combined with DA against platelet adhesion to endothelial cells (ECs), an essential step in thrombosis, remains unclear.
  
  
  OBJECTIVE
  To compare PQS combined with DA and DA alone in inhibiting platelet adhesion to injured human umbilical vein endothelial cells (HUVECs) and to explore the possible mechanisms focusing on PI3K/AKT, COX-2/6-keto-PGF1α, and COX-1/TXB2pathways.
  
  
  METHODS
  HUVECs injured by oxidized low-density lipoprotein (ox-LDL) were randomly allocated into control, model, DA, PQS+DA (P+DA), LY294002 (a PI3K inhibitor)+DA (L+DA), and LY294002+PQS+DA (LP+DA) groups. HUVEC apoptosis, platelet adhesion to injured HUVECs, and platelet CD62p expression were assayed by fluorescence activated cell sorting (FACS). The concentrations of 6-keto-PGF1αand TXB2in the supernatant were measured by radioimmunoassay. Protein expression of phosphorylated-PI3K, PI3K, phosphorylated-AKT, AKT, COX-1, and COX-2 in both platelets and HUVECs was evaluated by western blot.
  
  
  RESULTS
  Compared to DA alone, PQS combined with DA reduced platelet adhesion to HUVECs and HUVEC apoptosis more potently, increased the concentration of supernatant 6-keto-PGF1αand up-regulated phospho-AKT protein in HUVECs. LY294002 mitigated the effects of PQS on HUVEC apoptosis and platelet adhesion.
  
  
  CONCLUSIONS
  These findings show that PQS as a powerful supplement to DA, attenuated HUVEC apoptosis and improved the DA-mediated reduction of platelet adhesion to injured HUVECs and the underlying mechanisms may be associated with PI3K/AKT and COX pathways in HUVECs and platelets. PQS might provide a new complementary approach to improve the prognosis of thrombotic diseases in future.
authors.affiliation: Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Wang
authors.affiliation: Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China. Electronic address: meiar@126.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Xue
authors.affiliation: Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Na
authors.initials: N
authors.lastname: Kou
authors.affiliation: Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Xu
authors.affiliation: Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China. Electronic address: dz_shi@163.com.
authors.forename: Da-Zhuo
authors.initials: DZ
authors.lastname: Shi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D000077144:Clopidogrel; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004359:Drug Therapy, Combination; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000633:toxicity; D009025:Morpholines / Q000494:pharmacology; D019007:P-Selectin / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D008517:Phytotherapy; D010946:Plants, Medicinal; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D011460:Prostaglandins F / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013929:Thromboxane B2 / Q000378:metabolism; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D002867:Chromones; D008077:Lipoproteins, LDL; D009025:Morpholines; D019007:P-Selectin; C079995:Panax quinquefolium saponin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011460:Prostaglandins F; D047428:Protein Kinase Inhibitors; C546937:SELP protein, human; D012503:Saponins; C099252:oxidized low density lipoprotein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D013929:Thromboxane B2; D000077144:Clopidogrel; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D013988:Ticlopidine; D001241:Aspirin; C100006:prostaglandin F1
keywords: Cyclooxygenase; Dual antiplatelet; Endothelial cell; Panax quinquefolium saponin; Platelet adhesion; Thrombogenesis