Hinokitiol inhibits platelet activation ex vivo and thrombus formation in vivo

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• 作者：Kuan H. Lin^a ; ^b ; ¹ ; Jinn R. Kuo^c ; ¹ ; Wan J. Lu^b ; Chi L. Chung^d ; Duen S. Chou^b ; Shih Y. Huang^e ; Hsiu C. Lee^f ; ^g ; ^{hcjoyce.lee@gmail.com} ; Joen R. Sheu^b ; ^{sheujr@tmu.edu.tw}
• 关键词：BSA ; bovine serum albumin ; cPLA2 ; cytosolic phospholipase A2 ; CVDs ; cardiovascular diseases ; DAG ; diacylglycerol ; DTS ; the dense tubular system ; ERK ; extracellular signal-regulated kinase ; ESR ; electron spin resonance ; HO ; hydroxyl radical ; IP3 ; inositol
• 刊名：Biochemical Pharmacology
• 出版年：2013
• 出版时间：15 May, 2013
• 年：2013
• 卷：85
• 期：10
• 页码：1478-1485
• 全文大小：1487 K

文摘

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 ¦ÌM) 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)¦Ã2, 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 (OH) 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 ¦Á_IIb¦Â₃ 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 PLC¦Ã2-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.