Glabridin, a Bioactive Flavonoid from Licorice, Effectively Inhibits Platelet Activation in Humans and Mice
Platelets are crucial for hemostasis and arterial thrombosis, which may lead to severe cardiovascular diseases (CVDs). Thus, therapeutic agents must be developed to prevent pathological platelet activation. Glabridin, a major bioalkaloid extracted from licorice root, improves metabolic abnormalities...
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MDPI AG
2022-09-01
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author | Chi-Li Chung Jui-Hsuan Chen Wei-Chieh Huang Joen-Rong Sheu Chih-Wei Hsia Thanasekaran Jayakumar Chih-Hsuan Hsia Kuan-Rau Chiou Shaw-Min Hou |
author_facet | Chi-Li Chung Jui-Hsuan Chen Wei-Chieh Huang Joen-Rong Sheu Chih-Wei Hsia Thanasekaran Jayakumar Chih-Hsuan Hsia Kuan-Rau Chiou Shaw-Min Hou |
author_sort | Chi-Li Chung |
collection | DOAJ |
description | Platelets are crucial for hemostasis and arterial thrombosis, which may lead to severe cardiovascular diseases (CVDs). Thus, therapeutic agents must be developed to prevent pathological platelet activation. Glabridin, a major bioalkaloid extracted from licorice root, improves metabolic abnormalities (i.e., obesity and diabetes) and protects against CVDs and neuronal disorders. To the best of our knowledge, no studies have focused on glabridin’s effects on platelet activation. Therefore, we investigated these effects in humans and mice. Glabridin exhibited the highest inhibitory effects on collagen-stimulated platelet aggregation and moderate effects on arachidonic-acid-stimulated activation; however, no effects were observed for any other agonists (e.g., thrombin or U46619). Glabridin evidently reduced P-selectin expression, ATP release, and intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]i) mobilization and thromboxane A<sub>2</sub> formation; it further reduced the activation of phospholipase C (PLC)γ2/protein kinase C (PKC), phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β), mitogen-activated protein kinase (MAPK), and NF-κB. In mice, glabridin reduced the mortality rate caused by acute pulmonary thromboembolism without altering bleeding time. Thus, glabridin effectively inhibits the PLCγ2/PKC cascade and prevents the activation of the PI3K/Akt/GSK3β and MAPK pathways; this leads to a reduction in [Ca<sup>2+</sup>]i mobilization, which eventually inhibits platelet aggregation. Therefore, glabridin may be a promising therapeutic agent for thromboembolic disorders. |
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spelling | doaj.art-7f366bbcd2b5495d9a2a597196c7702d2023-11-23T20:32:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191137210.3390/ijms231911372Glabridin, a Bioactive Flavonoid from Licorice, Effectively Inhibits Platelet Activation in Humans and MiceChi-Li Chung0Jui-Hsuan Chen1Wei-Chieh Huang2Joen-Rong Sheu3Chih-Wei Hsia4Thanasekaran Jayakumar5Chih-Hsuan Hsia6Kuan-Rau Chiou7Shaw-Min Hou8Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, 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, TaiwanDepartment of Ecology and Environmental Sciences, Pondicherry University, Puducherry 605014, IndiaTranslational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, TaiwanDivision of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanPlatelets are crucial for hemostasis and arterial thrombosis, which may lead to severe cardiovascular diseases (CVDs). Thus, therapeutic agents must be developed to prevent pathological platelet activation. Glabridin, a major bioalkaloid extracted from licorice root, improves metabolic abnormalities (i.e., obesity and diabetes) and protects against CVDs and neuronal disorders. To the best of our knowledge, no studies have focused on glabridin’s effects on platelet activation. Therefore, we investigated these effects in humans and mice. Glabridin exhibited the highest inhibitory effects on collagen-stimulated platelet aggregation and moderate effects on arachidonic-acid-stimulated activation; however, no effects were observed for any other agonists (e.g., thrombin or U46619). Glabridin evidently reduced P-selectin expression, ATP release, and intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]i) mobilization and thromboxane A<sub>2</sub> formation; it further reduced the activation of phospholipase C (PLC)γ2/protein kinase C (PKC), phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β), mitogen-activated protein kinase (MAPK), and NF-κB. In mice, glabridin reduced the mortality rate caused by acute pulmonary thromboembolism without altering bleeding time. Thus, glabridin effectively inhibits the PLCγ2/PKC cascade and prevents the activation of the PI3K/Akt/GSK3β and MAPK pathways; this leads to a reduction in [Ca<sup>2+</sup>]i mobilization, which eventually inhibits platelet aggregation. Therefore, glabridin may be a promising therapeutic agent for thromboembolic disorders.https://www.mdpi.com/1422-0067/23/19/11372glabridinplateletMAPKmicrovascular thrombosisPI3K/Akt/GSK3βPLCγ2/PKC |
spellingShingle | Chi-Li Chung Jui-Hsuan Chen Wei-Chieh Huang Joen-Rong Sheu Chih-Wei Hsia Thanasekaran Jayakumar Chih-Hsuan Hsia Kuan-Rau Chiou Shaw-Min Hou Glabridin, a Bioactive Flavonoid from Licorice, Effectively Inhibits Platelet Activation in Humans and Mice International Journal of Molecular Sciences glabridin platelet MAPK microvascular thrombosis PI3K/Akt/GSK3β PLCγ2/PKC |
title | Glabridin, a Bioactive Flavonoid from Licorice, Effectively Inhibits Platelet Activation in Humans and Mice |
title_full | Glabridin, a Bioactive Flavonoid from Licorice, Effectively Inhibits Platelet Activation in Humans and Mice |
title_fullStr | Glabridin, a Bioactive Flavonoid from Licorice, Effectively Inhibits Platelet Activation in Humans and Mice |
title_full_unstemmed | Glabridin, a Bioactive Flavonoid from Licorice, Effectively Inhibits Platelet Activation in Humans and Mice |
title_short | Glabridin, a Bioactive Flavonoid from Licorice, Effectively Inhibits Platelet Activation in Humans and Mice |
title_sort | glabridin a bioactive flavonoid from licorice effectively inhibits platelet activation in humans and mice |
topic | glabridin platelet MAPK microvascular thrombosis PI3K/Akt/GSK3β PLCγ2/PKC |
url | https://www.mdpi.com/1422-0067/23/19/11372 |
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