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Article

Ligustrazine inhibits platelet activation via suppression of the Akt pathway

  • Authors:
    • Li Li
    • Hongwei Chen
    • Aling Shen
    • Qiongyu Li
    • Youqin Chen
    • Jianfeng Chu
    • Liya Liu
    • Jun Peng
    • Keji Chen
  • View Affiliations / Copyright

    Affiliations: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China, Department of Pediatric Gastroenterology, Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA, Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, P.R. China
  • Pages: 575-582
    |
    Published online on: November 1, 2018
       https://doi.org/10.3892/ijmm.2018.3970
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Abstract

Aberrant activation of platelets has a critical role in thrombotic vascular events, including atherosclerosis, arterial thrombosis and myocardial infarction. The process of platelet activation is associated with multiple intracellular signaling pathways, including the phosphoinositide 3‑kinase/AKT serine/threonine kinase (Akt) pathway. The well‑known medicinal herb Rhizoma Ligusticum Wallichii (RLW) has long been used in China to clinically treat various cardiovascular disorders. As the most pharmacologically active component of RLW, ligustrazine has been demonstrated to possess a potent antiplatelet activity. However, the precise mechanisms mediating the bioactivities of ligustrazine have not been thoroughly elucidated. The present study evaluated the effects of ligustrazine hydrochloride (LH; the clinical‑grade form of ligustrazine) on platelet activation and investigated the underlying molecular mechanisms. In vitro and ex vivo platelet activation models were used, established by stimulating rat platelet‑rich plasma either with the platelet activator adenosine diphosphate (ADP) or with the specific Akt pathway activator insulin‑like growth factor‑1 (IGF‑1). The results demonstrated that treatment with LH significantly and dose‑dependently inhibited ADP‑induced platelet aggregation, in addition to thromboxane A2 (TXA2) secretion and intracellular Ca2+ mobilization in platelets, in vitro and ex vivo. In addition, LH markedly suppressed ADP‑induced Akt phosphorylation in vitro and ex vivo. Furthermore, LH markedly inhibited IGF‑1‑induced Akt phosphorylation, platelet aggregation, TXA2 formation and Ca2+ mobilization in vitro. Finally, LH was able to reverse adrenaline‑induced shortening of bleeding time. Taken together, these results suggested that ligustrazine possesses a broad range of antiplatelet activities without apparent hemorrhagic side-effects, and suppression of Akt signaling may be one of the mechanisms by which ligustrazine exerts its antiplatelet activities.
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Copy and paste a formatted citation
Spandidos Publications style
Li L, Chen H, Shen A, Li Q, Chen Y, Chu J, Liu L, Peng J and Chen K: Ligustrazine inhibits platelet activation via suppression of the Akt pathway. Int J Mol Med 43: 575-582, 2019.
APA
Li, L., Chen, H., Shen, A., Li, Q., Chen, Y., Chu, J. ... Chen, K. (2019). Ligustrazine inhibits platelet activation via suppression of the Akt pathway. International Journal of Molecular Medicine, 43, 575-582. https://doi.org/10.3892/ijmm.2018.3970
MLA
Li, L., Chen, H., Shen, A., Li, Q., Chen, Y., Chu, J., Liu, L., Peng, J., Chen, K."Ligustrazine inhibits platelet activation via suppression of the Akt pathway". International Journal of Molecular Medicine 43.1 (2019): 575-582.
Chicago
Li, L., Chen, H., Shen, A., Li, Q., Chen, Y., Chu, J., Liu, L., Peng, J., Chen, K."Ligustrazine inhibits platelet activation via suppression of the Akt pathway". International Journal of Molecular Medicine 43, no. 1 (2019): 575-582. https://doi.org/10.3892/ijmm.2018.3970
Copy and paste a formatted citation
x
Spandidos Publications style
Li L, Chen H, Shen A, Li Q, Chen Y, Chu J, Liu L, Peng J and Chen K: Ligustrazine inhibits platelet activation via suppression of the Akt pathway. Int J Mol Med 43: 575-582, 2019.
APA
Li, L., Chen, H., Shen, A., Li, Q., Chen, Y., Chu, J. ... Chen, K. (2019). Ligustrazine inhibits platelet activation via suppression of the Akt pathway. International Journal of Molecular Medicine, 43, 575-582. https://doi.org/10.3892/ijmm.2018.3970
MLA
Li, L., Chen, H., Shen, A., Li, Q., Chen, Y., Chu, J., Liu, L., Peng, J., Chen, K."Ligustrazine inhibits platelet activation via suppression of the Akt pathway". International Journal of Molecular Medicine 43.1 (2019): 575-582.
Chicago
Li, L., Chen, H., Shen, A., Li, Q., Chen, Y., Chu, J., Liu, L., Peng, J., Chen, K."Ligustrazine inhibits platelet activation via suppression of the Akt pathway". International Journal of Molecular Medicine 43, no. 1 (2019): 575-582. https://doi.org/10.3892/ijmm.2018.3970
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