Decreased Human Platelet Activation and Mouse Pulmonary Thrombosis by Rutaecarpine and Comparison of the Relative Effectiveness with BAY11-7082: Crucial Signals of p38-NF-κB
Platelets play a critical role in arterial thrombosis. Rutaecarpine (RUT) was purified from <i>Tetradium ruticarpum</i>, a well-known Chinese medicine. This study examined the relative activity of RUT with NF-κB inhibitors in human platelets. BAY11-7082 (an inhibitor of IκB kinase [IKK])...
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MDPI AG
2022-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/2/476 |
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| author | Wei-Chieh Huang Shaw-Min Hou Ming-Ping Wu Chih-Wei Hsia Thanasekaran Jayakumar Chih-Hsuan Hsia Periyakali Saravana Bhavan Chi-Li Chung Joen-Rong Sheu |
| author_facet | Wei-Chieh Huang Shaw-Min Hou Ming-Ping Wu Chih-Wei Hsia Thanasekaran Jayakumar Chih-Hsuan Hsia Periyakali Saravana Bhavan Chi-Li Chung Joen-Rong Sheu |
| author_sort | Wei-Chieh Huang |
| collection | DOAJ |
| description | Platelets play a critical role in arterial thrombosis. Rutaecarpine (RUT) was purified from <i>Tetradium ruticarpum</i>, a well-known Chinese medicine. This study examined the relative activity of RUT with NF-κB inhibitors in human platelets. BAY11-7082 (an inhibitor of IκB kinase [IKK]), Ro106-9920 (an inhibitor of proteasomes), and RUT concentration-dependently (1–6 μM) inhibited platelet aggregation and P-selectin expression. RUT was found to have a similar effect to that of BAY11-7082; however, it exhibits more effectiveness than Ro106-9920. RUT suppresses the NF-κB pathway as it inhibits IKK, IκBα, and p65 phosphorylation and reverses IκBα degradation in activated platelets. This study also investigated the role of p38 and NF-κB in cell signaling events and found that SB203580 (an inhibitor of p38) markedly reduced p38, IKK, and p65 phosphorylation and reversed IκBα degradation as well as p65 activation in a confocal microscope, whereas BAY11-7082 had no effects in p38 phosphorylation. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay shows that RUT and BAY11-7082 did not exhibit free radical scavenging activity. In the in vivo study, compared with BAY11-7082, RUT more effectively reduced mortality in adenosine diphosphate (ADP)-induced acute pulmonary thromboembolism without affecting the bleeding time. In conclusion, a distinctive pathway of p38-mediated NF-κB activation may involve RUT-mediated antiplatelet activation, and RUT could act as a strong prophylactic or therapeutic drug for cardiovascular diseases. |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T00:50:17Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-bf18384d6c4d40eb9a4471f83b07b83c2023-11-23T14:52:35ZengMDPI AGMolecules1420-30492022-01-0127247610.3390/molecules27020476Decreased Human Platelet Activation and Mouse Pulmonary Thrombosis by Rutaecarpine and Comparison of the Relative Effectiveness with BAY11-7082: Crucial Signals of p38-NF-κBWei-Chieh Huang0Shaw-Min Hou1Ming-Ping Wu2Chih-Wei Hsia3Thanasekaran Jayakumar4Chih-Hsuan Hsia5Periyakali Saravana Bhavan6Chi-Li Chung7Joen-Rong Sheu8Graduate 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 Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanTranslational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, TaiwanDepartment of Zoology, Bharathiar University, Coimbatore 641046, Tamil Nadu, IndiaDepartment of Internal Medicine, Division of Pulmonary Medicine, Taipei Medical University Hospital, Taipei 110, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanPlatelets play a critical role in arterial thrombosis. Rutaecarpine (RUT) was purified from <i>Tetradium ruticarpum</i>, a well-known Chinese medicine. This study examined the relative activity of RUT with NF-κB inhibitors in human platelets. BAY11-7082 (an inhibitor of IκB kinase [IKK]), Ro106-9920 (an inhibitor of proteasomes), and RUT concentration-dependently (1–6 μM) inhibited platelet aggregation and P-selectin expression. RUT was found to have a similar effect to that of BAY11-7082; however, it exhibits more effectiveness than Ro106-9920. RUT suppresses the NF-κB pathway as it inhibits IKK, IκBα, and p65 phosphorylation and reverses IκBα degradation in activated platelets. This study also investigated the role of p38 and NF-κB in cell signaling events and found that SB203580 (an inhibitor of p38) markedly reduced p38, IKK, and p65 phosphorylation and reversed IκBα degradation as well as p65 activation in a confocal microscope, whereas BAY11-7082 had no effects in p38 phosphorylation. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay shows that RUT and BAY11-7082 did not exhibit free radical scavenging activity. In the in vivo study, compared with BAY11-7082, RUT more effectively reduced mortality in adenosine diphosphate (ADP)-induced acute pulmonary thromboembolism without affecting the bleeding time. In conclusion, a distinctive pathway of p38-mediated NF-κB activation may involve RUT-mediated antiplatelet activation, and RUT could act as a strong prophylactic or therapeutic drug for cardiovascular diseases.https://www.mdpi.com/1420-3049/27/2/476DPPHhuman plateletsp38 MAPKNF-κBpulmonary thrombosisrutaecarpine |
| spellingShingle | Wei-Chieh Huang Shaw-Min Hou Ming-Ping Wu Chih-Wei Hsia Thanasekaran Jayakumar Chih-Hsuan Hsia Periyakali Saravana Bhavan Chi-Li Chung Joen-Rong Sheu Decreased Human Platelet Activation and Mouse Pulmonary Thrombosis by Rutaecarpine and Comparison of the Relative Effectiveness with BAY11-7082: Crucial Signals of p38-NF-κB Molecules DPPH human platelets p38 MAPK NF-κB pulmonary thrombosis rutaecarpine |
| title | Decreased Human Platelet Activation and Mouse Pulmonary Thrombosis by Rutaecarpine and Comparison of the Relative Effectiveness with BAY11-7082: Crucial Signals of p38-NF-κB |
| title_full | Decreased Human Platelet Activation and Mouse Pulmonary Thrombosis by Rutaecarpine and Comparison of the Relative Effectiveness with BAY11-7082: Crucial Signals of p38-NF-κB |
| title_fullStr | Decreased Human Platelet Activation and Mouse Pulmonary Thrombosis by Rutaecarpine and Comparison of the Relative Effectiveness with BAY11-7082: Crucial Signals of p38-NF-κB |
| title_full_unstemmed | Decreased Human Platelet Activation and Mouse Pulmonary Thrombosis by Rutaecarpine and Comparison of the Relative Effectiveness with BAY11-7082: Crucial Signals of p38-NF-κB |
| title_short | Decreased Human Platelet Activation and Mouse Pulmonary Thrombosis by Rutaecarpine and Comparison of the Relative Effectiveness with BAY11-7082: Crucial Signals of p38-NF-κB |
| title_sort | decreased human platelet activation and mouse pulmonary thrombosis by rutaecarpine and comparison of the relative effectiveness with bay11 7082 crucial signals of p38 nf κb |
| topic | DPPH human platelets p38 MAPK NF-κB pulmonary thrombosis rutaecarpine |
| url | https://www.mdpi.com/1420-3049/27/2/476 |
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