title: Honokiol as a specific collagen receptor glycoprotein VI antagonist on human platelets: Functional ex vivo and in vivo studies.
abstract: Honokiol, derived from Magnolia officinalis, has various pharmacological properties. Platelet activation plays a critical role in cardiovascular diseases. Honokiol has been reported to inhibit collagen-stimulated rabbit platelet aggregation. However, detailed further studies on the characteristics and functional activity of honokiol in platelet activation are relatively lacking. In the present study, honokiol specifically inhibited platelet aggregation and Ca+2ion mobilization stimulated with collagen or convulxin, an agonist of glycoprotein (GP) VI, but not with aggretin, an agonist of integrin α2β1. Honokiol also attenuated the phosphorylation of Lyn, PLCγ2, PKC, MAPKs, and Akt after convulxin stimulation. Honokiol have no cytotoxicity in zebrafish embryos. Honokiol diminished the binding of anti-GP VI (FITC-JAQ1) mAb to human platelets, and it also reduced the coimmunoprecipitation of GP VI-bound Lyn after convulxin stimulation. The surface plasmon resonance results revealed that honokiol binds directly to GP VI, with a KDof 289 μM. Platelet function analysis revealed that honokiol substantially prolonged the closure time in human whole blood and increased the occlusion time of thrombotic platelet plug formation in mice. In conclusion, honokiol acts as a potent antagonist of collagen GP VI in human platelets, and it has therapeutic potential in the prevention of the pathological thrombosis.
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tzu-Yin
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of Cardiology, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Chao-Chien
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Wan-Jung
authors.initials: WJ
authors.lastname: Lu
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ting-Lin
authors.initials: TL
authors.lastname: Yen
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Kuan-Hung
authors.initials: KH
authors.lastname: Lin
authors.affiliation: Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India.
authors.forename: Pitchairaj
authors.initials: P
authors.lastname: Geraldine
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Cardiovascular Surgery, Mackay Memorial Hospital, and Mackay Medical College, Taipei, Taiwan.
authors.forename: Jiun-Yi
authors.initials: JY
authors.lastname: Li
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D017705:Lignans / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects*; D011485:Protein Binding; D038981:Receptors, Collagen / Q000037:antagonists & inhibitors*; D020349:Surface Plasmon Resonance; D013927:Thrombosis / Q000517:prevention & control; D015027:Zebrafish; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D017705:Lignans; D038981:Receptors, Collagen; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols