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Research ArticleCardiovascular

Novel Antiplatelet Activity of Protocatechuic Acid through the Inhibition of High Shear Stress-Induced Platelet Aggregation

Keunyoung Kim, Ok-Nam Bae, Kyung-Min Lim, Ji-Yoon Noh, Seojin Kang, Ka Young Chung and Jin-Ho Chung
Journal of Pharmacology and Experimental Therapeutics December 2012, 343 (3) 704-711; DOI: https://doi.org/10.1124/jpet.112.198242
Keunyoung Kim
College of Pharmacy, Seoul National University, Seoul, Korea (K.K., K.-M.L., J.-Y.N., S.K., J.-H.C.); School of Pharmacy, Sungkyunkwan University, Suwon, Korea (K.Y.C.); and College of Pharmacy, Hanyang University, Ansan, Korea (O.-N.B.)
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Ok-Nam Bae
College of Pharmacy, Seoul National University, Seoul, Korea (K.K., K.-M.L., J.-Y.N., S.K., J.-H.C.); School of Pharmacy, Sungkyunkwan University, Suwon, Korea (K.Y.C.); and College of Pharmacy, Hanyang University, Ansan, Korea (O.-N.B.)
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Kyung-Min Lim
College of Pharmacy, Seoul National University, Seoul, Korea (K.K., K.-M.L., J.-Y.N., S.K., J.-H.C.); School of Pharmacy, Sungkyunkwan University, Suwon, Korea (K.Y.C.); and College of Pharmacy, Hanyang University, Ansan, Korea (O.-N.B.)
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Ji-Yoon Noh
College of Pharmacy, Seoul National University, Seoul, Korea (K.K., K.-M.L., J.-Y.N., S.K., J.-H.C.); School of Pharmacy, Sungkyunkwan University, Suwon, Korea (K.Y.C.); and College of Pharmacy, Hanyang University, Ansan, Korea (O.-N.B.)
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Seojin Kang
College of Pharmacy, Seoul National University, Seoul, Korea (K.K., K.-M.L., J.-Y.N., S.K., J.-H.C.); School of Pharmacy, Sungkyunkwan University, Suwon, Korea (K.Y.C.); and College of Pharmacy, Hanyang University, Ansan, Korea (O.-N.B.)
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Ka Young Chung
College of Pharmacy, Seoul National University, Seoul, Korea (K.K., K.-M.L., J.-Y.N., S.K., J.-H.C.); School of Pharmacy, Sungkyunkwan University, Suwon, Korea (K.Y.C.); and College of Pharmacy, Hanyang University, Ansan, Korea (O.-N.B.)
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Jin-Ho Chung
College of Pharmacy, Seoul National University, Seoul, Korea (K.K., K.-M.L., J.-Y.N., S.K., J.-H.C.); School of Pharmacy, Sungkyunkwan University, Suwon, Korea (K.Y.C.); and College of Pharmacy, Hanyang University, Ansan, Korea (O.-N.B.)
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Abstract

Bleeding is the most common and serious adverse effect of currently available antiplatelet drugs. Many efforts are being made to develop novel antithrombotic agents without bleeding risks. Shear stress-induced platelet aggregation (SIPA), which occurs under abnormally high shear stress, plays a crucial role in the development of arterial thrombotic diseases. Here, we demonstrate that protocatechuic acid (PCA), a bioactive phytochemical from Lonicera (honeysuckle) flowers, selectively and potently inhibits high shear (>10,000 s−1)-induced platelet aggregation. In isolated human platelets, PCA decreased SIPA and attenuated accompanying platelet activation, including intracellular calcium mobilization, granule secretion, and adhesion receptor expression. The anti-SIPA effect of PCA was mediated through blockade of von Willebrand factor binding to activated glycoprotein Ib, a primary and initial event for the accomplishment of SIPA. Conspicuously, PCA did not inhibit platelet aggregation induced by other endogenous agonists like collagen, thrombin, or ADP that are important in both pathological thrombosis and normal hemostasis. Antithrombotic effects of PCA were confirmed in vivo in a rat arterial thrombosis model, where PCA significantly delayed the arterial occlusion induced by FeCl3. Of particular note, PCA did not increase bleeding times in a rat tail transection model, whereas conventional antiplatelet drugs, aspirin, and clopidogrel substantially prolonged it. Collectively, these results suggest that PCA may be a novel antiplatelet agent that can prevent thrombosis without increasing bleeding risks.

Footnotes

  • This work was supported by the National Research Foundation of Korea, which is funded by the Korean government [Grant 20120000844].

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    http://dx.doi.org/10.1124/jpet.112.198242.

  • ABBREVIATIONS:

    SIPA
    shear stress-induced platelet aggregation
    Ab
    antibody
    AM
    acetoxymethyl ester
    FITC
    fluorescein isothiocyanate
    GP
    glycoprotein
    LDH
    lactate dehydrogenase
    PCA
    protocatechuic acid
    PE
    phycoerythrin
    PGE1
    prostaglandin E1
    PRP
    platelet-rich plasma
    vWF
    von Willebrand factor
    WP
    washed platelet.

  • Received July 8, 2012.
  • Accepted September 4, 2012.
  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 343 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 343, Issue 3
1 Dec 2012
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Research ArticleCardiovascular

Novel Antiplatelet Effect of Protocatechuic Acid

Keunyoung Kim, Ok-Nam Bae, Kyung-Min Lim, Ji-Yoon Noh, Seojin Kang, Ka Young Chung and Jin-Ho Chung
Journal of Pharmacology and Experimental Therapeutics December 1, 2012, 343 (3) 704-711; DOI: https://doi.org/10.1124/jpet.112.198242

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Research ArticleCardiovascular

Novel Antiplatelet Effect of Protocatechuic Acid

Keunyoung Kim, Ok-Nam Bae, Kyung-Min Lim, Ji-Yoon Noh, Seojin Kang, Ka Young Chung and Jin-Ho Chung
Journal of Pharmacology and Experimental Therapeutics December 1, 2012, 343 (3) 704-711; DOI: https://doi.org/10.1124/jpet.112.198242
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