1. Academic Validation
  2. Honokiol as a specific collagen receptor glycoprotein VI antagonist on human platelets: Functional ex vivo and in vivo studies

Honokiol as a specific collagen receptor glycoprotein VI antagonist on human platelets: Functional ex vivo and in vivo studies

  • Sci Rep. 2017 Jan 5;7:40002. doi: 10.1038/srep40002.
Tzu-Yin Lee 1 Chao-Chien Chang 1 2 Wan-Jung Lu 1 3 Ting-Lin Yen 1 Kuan-Hung Lin 1 4 Pitchairaj Geraldine 5 Jiun-Yi Li 1 6 Joen-Rong Sheu 1
Affiliations

Affiliations

  • 1 Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 2 Division of Cardiology, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan.
  • 3 Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan.
  • 4 Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
  • 5 Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India.
  • 6 Department of Cardiovascular Surgery, Mackay Memorial Hospital, and Mackay Medical College, Taipei, Taiwan.
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+2 ion 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 KD of 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.

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