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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\u2019s 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 Ca2+ ([Ca2+]i) mobilization and thromboxane A2 formation; it further reduced the activation of phospholipase C (PLC)\u03b32\/protein kinase C (PKC), phosphoinositide 3-kinase (PI3K)\/Akt\/glycogen synthase kinase-3\u03b2 (GSK3\u03b2), mitogen-activated protein kinase (MAPK), and NF-\u03baB. In mice, glabridin reduced the mortality rate caused by acute pulmonary thromboembolism without altering bleeding time. Thus, glabridin effectively inhibits the PLC\u03b32\/PKC cascade and prevents the activation of the PI3K\/Akt\/GSK3\u03b2 and MAPK pathways; this leads to a reduction in [Ca2+]i mobilization, which eventually inhibits platelet aggregation. Therefore, glabridin may be a promising therapeutic agent for thromboembolic disorders.<\/jats:p>","DOI":"10.3390\/ijms231911372","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T23:12:12Z","timestamp":1664320332000},"page":"11372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Glabridin, a Bioactive Flavonoid from Licorice, Effectively Inhibits Platelet Activation in Humans and Mice"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0656-976X","authenticated-orcid":false,"given":"Chi-Li","family":"Chung","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Hsuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Chieh","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8265-3678","authenticated-orcid":false,"given":"Joen-Rong","family":"Sheu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4508-6181","authenticated-orcid":false,"given":"Chih-Wei","family":"Hsia","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanasekaran","family":"Jayakumar","sequence":"additional","affiliation":[{"name":"Department of Ecology and Environmental Sciences, Pondicherry University, Puducherry 605014, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hsuan","family":"Hsia","sequence":"additional","affiliation":[{"name":"Translational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Rau","family":"Chiou","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaw-Min","family":"Hou","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Cardiovascular Center, Cathay General Hospital, Taipei 106, Taiwan"},{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1097\/MOH.0b013e328364219d","article-title":"Inflammation and thrombosis in cardiovascular disease","volume":"20","author":"Nagareddy","year":"2013","journal-title":"Curr. 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