Reduction of NF-κB Signals in Platelets and Prolongation of Platelet Plug Formation against High Shear Flow in Whole Blood on Human Subject by Columbianadin
Myocardial infarction and cerebral ischemic stroke during the process of arterial thrombosis are prominently causes of death worldwide. Platelets are anucleated cells and play a critical factor in these diseases. Columbianadin (CBN), a coumarin derivative from plants, inhibits effective platelet act...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | Applied Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3417/10/20/7323 |
| _version_ | 1797550431677710336 |
|---|---|
| author | Chih-Wei Hsia Chih-Hao Yang Joen-Rong Sheu Chih-Hsuan Hsia Cheng-Lin Tsai Wei-Chieh Huang Ting-Yu Chen Thanasekaran Jayakumar Periyakali Saravana Bhavan Yi Chang |
| author_facet | Chih-Wei Hsia Chih-Hao Yang Joen-Rong Sheu Chih-Hsuan Hsia Cheng-Lin Tsai Wei-Chieh Huang Ting-Yu Chen Thanasekaran Jayakumar Periyakali Saravana Bhavan Yi Chang |
| author_sort | Chih-Wei Hsia |
| collection | DOAJ |
| description | Myocardial infarction and cerebral ischemic stroke during the process of arterial thrombosis are prominently causes of death worldwide. Platelets are anucleated cells and play a critical factor in these diseases. Columbianadin (CBN), a coumarin derivative from plants, inhibits effective platelet activation. In this study, platelet function analysis revealed that the closure time of the platelet plug in human whole blood significantly prolonged by CBN, whereas CBN did not pointedly prolong the bleeding time in mice. BAY11-7082 (an inhibitor of IκB kinase) and MG-132 (an inhibitor of proteasome) inhibited collagen-stimulated platelet aggregation and ATP-release in human platelets, BAY11-7082 exhibited a higher potency than MG-132. Moreover, CBN markedly reduced NF-κB activation (e.g., IκBα and p65 phosphorylation) and reversed IκBα degradation in activated platelets. We investigated intercellular signaling events between mitogen-activated protein kinases and NF-κB, and found that BAY11-7082 abolished JNK1/2 and ERK1/2 phosphorylation. Interestingly, SP600125 (an inhibitor of JNK) but not PD98059 (an inhibitor of ERK) had no effect in NF-κB activation in activated platelets. Moreover, CBN but not BAY11-7082 significantly reduced hydroxyl radical (HO<sup>●</sup>) formation in platelets. Therefore, we propose that CBN inhibits NF-κB activation in human platelets and could present a potent clinical treatment for thromboembolic diseases. |
| first_indexed | 2024-03-10T15:29:12Z |
| format | Article |
| id | doaj.art-073080b048944be38ab16cda79dc5fb7 |
| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-10T15:29:12Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-073080b048944be38ab16cda79dc5fb72023-11-20T17:43:51ZengMDPI AGApplied Sciences2076-34172020-10-011020732310.3390/app10207323Reduction of NF-κB Signals in Platelets and Prolongation of Platelet Plug Formation against High Shear Flow in Whole Blood on Human Subject by ColumbianadinChih-Wei Hsia0Chih-Hao Yang1Joen-Rong Sheu2Chih-Hsuan Hsia3Cheng-Lin Tsai4Wei-Chieh Huang5Ting-Yu Chen6Thanasekaran Jayakumar7Periyakali Saravana Bhavan8Yi Chang9Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanGraduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 110, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanDepartment of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanDepartment of Zoology, Bharathiar University, Coimbatore, Tamil Nadu 641046, IndiaGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanMyocardial infarction and cerebral ischemic stroke during the process of arterial thrombosis are prominently causes of death worldwide. Platelets are anucleated cells and play a critical factor in these diseases. Columbianadin (CBN), a coumarin derivative from plants, inhibits effective platelet activation. In this study, platelet function analysis revealed that the closure time of the platelet plug in human whole blood significantly prolonged by CBN, whereas CBN did not pointedly prolong the bleeding time in mice. BAY11-7082 (an inhibitor of IκB kinase) and MG-132 (an inhibitor of proteasome) inhibited collagen-stimulated platelet aggregation and ATP-release in human platelets, BAY11-7082 exhibited a higher potency than MG-132. Moreover, CBN markedly reduced NF-κB activation (e.g., IκBα and p65 phosphorylation) and reversed IκBα degradation in activated platelets. We investigated intercellular signaling events between mitogen-activated protein kinases and NF-κB, and found that BAY11-7082 abolished JNK1/2 and ERK1/2 phosphorylation. Interestingly, SP600125 (an inhibitor of JNK) but not PD98059 (an inhibitor of ERK) had no effect in NF-κB activation in activated platelets. Moreover, CBN but not BAY11-7082 significantly reduced hydroxyl radical (HO<sup>●</sup>) formation in platelets. Therefore, we propose that CBN inhibits NF-κB activation in human platelets and could present a potent clinical treatment for thromboembolic diseases.https://www.mdpi.com/2076-3417/10/20/7323columbianadinhuman plateletshydroxyl radicalERK1/2JNK1/2NF-κB |
| spellingShingle | Chih-Wei Hsia Chih-Hao Yang Joen-Rong Sheu Chih-Hsuan Hsia Cheng-Lin Tsai Wei-Chieh Huang Ting-Yu Chen Thanasekaran Jayakumar Periyakali Saravana Bhavan Yi Chang Reduction of NF-κB Signals in Platelets and Prolongation of Platelet Plug Formation against High Shear Flow in Whole Blood on Human Subject by Columbianadin Applied Sciences columbianadin human platelets hydroxyl radical ERK1/2 JNK1/2 NF-κB |
| title | Reduction of NF-κB Signals in Platelets and Prolongation of Platelet Plug Formation against High Shear Flow in Whole Blood on Human Subject by Columbianadin |
| title_full | Reduction of NF-κB Signals in Platelets and Prolongation of Platelet Plug Formation against High Shear Flow in Whole Blood on Human Subject by Columbianadin |
| title_fullStr | Reduction of NF-κB Signals in Platelets and Prolongation of Platelet Plug Formation against High Shear Flow in Whole Blood on Human Subject by Columbianadin |
| title_full_unstemmed | Reduction of NF-κB Signals in Platelets and Prolongation of Platelet Plug Formation against High Shear Flow in Whole Blood on Human Subject by Columbianadin |
| title_short | Reduction of NF-κB Signals in Platelets and Prolongation of Platelet Plug Formation against High Shear Flow in Whole Blood on Human Subject by Columbianadin |
| title_sort | reduction of nf κb signals in platelets and prolongation of platelet plug formation against high shear flow in whole blood on human subject by columbianadin |
| topic | columbianadin human platelets hydroxyl radical ERK1/2 JNK1/2 NF-κB |
| url | https://www.mdpi.com/2076-3417/10/20/7323 |
| work_keys_str_mv | AT chihweihsia reductionofnfkbsignalsinplateletsandprolongationofplateletplugformationagainsthighshearflowinwholebloodonhumansubjectbycolumbianadin AT chihhaoyang reductionofnfkbsignalsinplateletsandprolongationofplateletplugformationagainsthighshearflowinwholebloodonhumansubjectbycolumbianadin AT joenrongsheu reductionofnfkbsignalsinplateletsandprolongationofplateletplugformationagainsthighshearflowinwholebloodonhumansubjectbycolumbianadin AT chihhsuanhsia reductionofnfkbsignalsinplateletsandprolongationofplateletplugformationagainsthighshearflowinwholebloodonhumansubjectbycolumbianadin AT chenglintsai reductionofnfkbsignalsinplateletsandprolongationofplateletplugformationagainsthighshearflowinwholebloodonhumansubjectbycolumbianadin AT weichiehhuang reductionofnfkbsignalsinplateletsandprolongationofplateletplugformationagainsthighshearflowinwholebloodonhumansubjectbycolumbianadin AT tingyuchen reductionofnfkbsignalsinplateletsandprolongationofplateletplugformationagainsthighshearflowinwholebloodonhumansubjectbycolumbianadin AT thanasekaranjayakumar reductionofnfkbsignalsinplateletsandprolongationofplateletplugformationagainsthighshearflowinwholebloodonhumansubjectbycolumbianadin AT periyakalisaravanabhavan reductionofnfkbsignalsinplateletsandprolongationofplateletplugformationagainsthighshearflowinwholebloodonhumansubjectbycolumbianadin AT yichang reductionofnfkbsignalsinplateletsandprolongationofplateletplugformationagainsthighshearflowinwholebloodonhumansubjectbycolumbianadin |