Hinokitiol inhibits platelet activation ex vivo and thrombus formation in vivo

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題名:	Hinokitiol inhibits platelet activation ex vivo and thrombus formation in vivo
作者:	Kuan H. Lin;Jinn R. Kuo;Wan J. Lu;Chi L. Chung;Duen S. Chou;Shih Y. Huang;Hsiu C. Lee;Joen R. Sheu
貢獻者:	視光學系
關鍵詞:	Hinokitiol;Hydroxyl radical;MAPK;Occlusion time;Platelet activation;PLCγ2
日期:	2013-05-01
上傳時間:	2025-08-01 15:07:02 (UTC+8)
摘要:	Hinokitiol is a tropolone-related bioactive compound that has been used in hair tonics, cosmetics, and food as an antimicrobial agent. Recently, hinokitiol has attracted considerable interest because of its anticancer activities. Platelet activation plays a crucial role in atherothrombotic processes. We examined the effects of hinokitiol treatment on platelet activation using human platelets. In the present study, hinokitiol (1 and 2 μM) inhibited the collagen-induced aggregation of human platelets, but did not inhibit the activation of platelets by other agonists, including thrombin, arachidonic acid, and ADP. Hinokitiol inhibited the phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and Akt in collagen-activated human platelets, and significantly reduced intracellular calcium mobilization and hydroxyl radical (OHradical dot) formation. Hinokitiol also reduced the PKC activation and platelet aggregation stimulated by PDBu. In addition, hinokitiol significantly prolonged thrombogenesis in mice. Hinokitiol did not influence the binding of a fluorescent triflavin probe to the αIIbβ3 integrin on platelet membrane, and neither ODQ nor SQ22536 significantly reversed the hinokitiol-mediated inhibition of platelet aggregation. In conclusion, hinokitiol may inhibit platelet activation by inhibiting the PLCγ2-PKC cascade and hydroxyl radical formation, followed by suppressing the activation of MAPKs and Akt. Our study suggests that hinokitiol may represent a potential therapeutic agent for the prevention or treatment of thromboembolic disorders.
關聯:	Biochemical Pharmacology, 85(10), 1478-1485. https://doi.org/10.1016/j.bcp.2013.02.027
顯示於類別:	[視光學系] 期刊論文

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