Abstract

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 (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 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. AbbreviationsBSAbovine serum albumincPLA2cytosolic phospholipase A 2CVDscardiovascular diseasesDAGdiacylglycerolDTSthe dense tubular systemERKextracellular signal-regulated kinaseESRelectron spin resonanceHOhydroxyl radicalIP3inositol 1,4,5-trisphosphateJNKc-Jun N-terminal kinaseNTGnitroglycerinPGE1prostaglandin E 1PKCprotein kinase CPRPplatelet-rich plasmaTxA2thromboxane A2.

Original languageEnglish
Pages (from-to)1478-1485
Number of pages8
JournalBiochemical Pharmacology
Volume85
Issue number10
DOIs
Publication statusPublished - May 15 2013

Fingerprint

Platelet Activation
Platelets
Thrombosis
Chemical activation
Platelet Aggregation
Protein Kinase C
Blood Platelets
Agglomeration
Mitogen-Activated Protein Kinases
Hydroxyl Radical
Hair Preparations
beta-thujaplicin
Collagen
Tropolone
Phosphorylation
Cosmetics
Phospholipases A
Type C Phospholipases
Anti-Infective Agents
Fluorescent Dyes

Keywords

  • Hinokitiol
  • Hydroxyl radical
  • MAPK
  • Occlusion time
  • Platelet activation
  • PLCγ2

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

Cite this

Hinokitiol inhibits platelet activation ex vivo and thrombus formation in vivo. / Lin, Kuan H.; Kuo, Jinn R.; Lu, Wan-Jung; Chung, Chi L.; Chou, Duen S.; Huang, Shih Y.; Lee, Hsiu C.; Sheu, Joen R.

In: Biochemical Pharmacology, Vol. 85, No. 10, 15.05.2013, p. 1478-1485.

Research output: Contribution to journalArticle

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abstract = "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 (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 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. AbbreviationsBSAbovine serum albumincPLA2cytosolic phospholipase A 2CVDscardiovascular diseasesDAGdiacylglycerolDTSthe dense tubular systemERKextracellular signal-regulated kinaseESRelectron spin resonanceHOhydroxyl radicalIP3inositol 1,4,5-trisphosphateJNKc-Jun N-terminal kinaseNTGnitroglycerinPGE1prostaglandin E 1PKCprotein kinase CPRPplatelet-rich plasmaTxA2thromboxane A2.",
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author = "Lin, {Kuan H.} and Kuo, {Jinn R.} and Wan-Jung Lu and Chung, {Chi L.} and Chou, {Duen S.} and Huang, {Shih Y.} and Lee, {Hsiu C.} and Sheu, {Joen R.}",
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T1 - Hinokitiol inhibits platelet activation ex vivo and thrombus formation in vivo

AU - Lin, Kuan H.

AU - Kuo, Jinn R.

AU - Lu, Wan-Jung

AU - Chung, Chi L.

AU - Chou, Duen S.

AU - Huang, Shih Y.

AU - Lee, Hsiu C.

AU - Sheu, Joen R.

PY - 2013/5/15

Y1 - 2013/5/15

N2 - 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 (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 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. AbbreviationsBSAbovine serum albumincPLA2cytosolic phospholipase A 2CVDscardiovascular diseasesDAGdiacylglycerolDTSthe dense tubular systemERKextracellular signal-regulated kinaseESRelectron spin resonanceHOhydroxyl radicalIP3inositol 1,4,5-trisphosphateJNKc-Jun N-terminal kinaseNTGnitroglycerinPGE1prostaglandin E 1PKCprotein kinase CPRPplatelet-rich plasmaTxA2thromboxane A2.

AB - 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 (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 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. AbbreviationsBSAbovine serum albumincPLA2cytosolic phospholipase A 2CVDscardiovascular diseasesDAGdiacylglycerolDTSthe dense tubular systemERKextracellular signal-regulated kinaseESRelectron spin resonanceHOhydroxyl radicalIP3inositol 1,4,5-trisphosphateJNKc-Jun N-terminal kinaseNTGnitroglycerinPGE1prostaglandin E 1PKCprotein kinase CPRPplatelet-rich plasmaTxA2thromboxane A2.

KW - Hinokitiol

KW - Hydroxyl radical

KW - MAPK

KW - Occlusion time

KW - Platelet activation

KW - PLCγ2

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