{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:01:12Z","timestamp":1792728072781,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["2022R1A2C1012963"],"award-info":[{"award-number":["2022R1A2C1012963"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2024,2,9]]},"abstract":"<jats:p>Cardiovascular diseases (CVDs) have been the major cause of mortality all around the globe. Lespedeza cuneata abbreviated as L. cuneata with the authority name of Dumont de Courset (G. Don) is a perennial flowering plant commonly grown in Asian countries such as Korea, Japan, China, and Taiwan. We aimed to investigate the L. cuneata extract\u2019s antiplatelet and antithrombotic properties as GC-MS analysis indicated that the extract contained short-chain fatty acids, which have been reported to possess beneficial cardiovascular effects. L. cuneata was extracted using water, 50% EtOH, 70% EtOH, and 100% EtOH. For in vitro antiplatelet analysis, washed platelets were prepared and incubated with L. cuneata with 200\u2009\u03bcg\/mL of 50% EtOH in the presence of 1\u2009mM of CaCl2 for 1\u2009minute followed by agonist (collagen 2.5\u2009\u03bcg\/mL or ADP 10\u2009\u03bcM or thrombin 0.1\u2009U\/mL) stimulation for 5\u2009minutes over light transmission aggregometer. Scanning electron microscopy was performed to assess platelet shape change. ATP release and intracellular calcium mobilization were quantified to assess the granular content. Fibrinogen-binding assay and clot retraction assay assessed integrin \u03b1IIb\u03b23-mediated inside-out and outside-in signaling. Protein phosphorylation expression was investigated by western blot analysis. Finally, the in vivo antithrombotic efficacy was investigated by oral dosage of L. cuneata 200 and 400\u2009mg\/kg and aspirin 100\u2009mg\/kg for 7\u2009days, and tail bleeding and FeCl3-induced murine thrombus model were performed. In vitro platelet aggregation and platelet shape change were dose-dependently suppressed by L. cuneata. Calcium mobilization, dense granules secretion, integrin \u03b1IIb\u03b23-mediated inside-out and outside-in signaling, and protein phosphorylation of MAPK and PI3K\/Akt pathways were significantly inhibited. In vivo assays revealed that L. cuneata prevents side effects of synthetic drugs via nonsignificantly increasing bleeding time and improving coronary artery blood flow and animal survival. Our results demonstrate that L. cuneata exhibited potent antiplatelet and antithrombotic effects and can be considered a potential herbal medicine with cardioprotective effects.<\/jats:p>","DOI":"10.1155\/2024\/9927160","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T15:50:10Z","timestamp":1707493810000},"page":"1-13","source":"Crossref","is-referenced-by-count":9,"title":["Antiplatelet and Antithrombotic Activities of Lespedeza cuneata via Pharmacological Inhibition of Integrin \u03b1IIb\u03b23, MAPK, and PI3K\/AKT Pathways and FeCl3-Induced Murine Thrombosis"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0244-1945","authenticated-orcid":true,"given":"Abdul Wahab","family":"Akram","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0012-1895","authenticated-orcid":true,"given":"Evelyn","family":"Saba","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biomedical Sciences, Faculty of Veterinary and Animal Sciences, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3088-1318","authenticated-orcid":true,"given":"Man Hee","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"},{"name":"Companion Animal Medical Institute, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","article-title":"The underlying cause of death 1999-2013 on cdc wonder online database, released 2015","author":"heartdisease","year":"2013"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000950"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001123"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.26599\/1671-5411.2023.06.006"},{"key":"5","article-title":"European alliance for cardiovascular health","author":"cardiovascular","year":"2024"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2023.38.e119"},{"key":"7","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1055\/s-0030-1251500","article-title":"Platelet-derived chemokines in vascular remodeling and atherosclerosis","volume":"36","author":"R. R. Koenen","year":"2010","journal-title":"Seminars in Thrombosis and hemostasis"},{"issue":"9","key":"8","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1056\/NEJMoa1204133","article-title":"Effects of clopidogrel added to aspirin in patients with recent lacunar stroke","volume":"367","author":"S. Investigators","year":"2012","journal-title":"New England Journal of Medicine"},{"issue":"3","key":"9","first-page":"313","article-title":"Aspirin and clopidogrel response variability: review of the published literature","volume":"35","author":"A. D. Ferguson","year":"2008","journal-title":"Texas Heart Institute Journal"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-233932"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-453134"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jarmap.2022.100400"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi684"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2017.10.004"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2020.03.001"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.14405\/kjvr.20230022"},{"issue":"6","key":"17","first-page":"735","article-title":"A study on effects of Lespedeza cuneata extract on the improvement of scalp conditions in adult Men in Their 30\u223c 40s","volume":"13","author":"N. Kim","year":"2015","journal-title":"Journal of the Korean Society of Cosmetology"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2018.1564929"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1039\/c7fo01666b"},{"key":"20","first-page":"34","article-title":"The effect of Lespedeza cuneata extract for antioxidative and whitening effect","volume":"28","author":"E. J. Cho","year":"2009","journal-title":"International Journal of Life Science Research Archive"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00698"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2018.1479033"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-307-3_8"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000261936.85776.5f"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2022.01.001"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2021.62.11.1032"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0935"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.2165\/00129784-200505060-00007"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00059"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1017\/S1431927616000854"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2009.04.001"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1994.tb02418.x"},{"issue":"11","key":"33","first-page":"2369","article-title":"The anti-platelet activity of Hypsizygus marmoreus extract is involved in the suppression of intracellular calcium mobilization and integrin \u03b1IIb\u03b23 activation","volume":"5","author":"J. Y. Park","year":"2011","journal-title":"Journal of Medicinal Plants Research"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e318070d1bd"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.300570"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03169.x"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.706363"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105047"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14091-4"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1039\/c5fo00327j"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00563.2006"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21145088"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110381"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2018.03.056"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-7803"}],"container-title":["Evidence-Based Complementary and Alternative Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2024\/9927160.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2024\/9927160.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2024\/9927160.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T15:50:16Z","timestamp":1707493816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/ecam\/2024\/9927160\/"}},"subtitle":[],"editor":[{"given":"Sultan","family":"Zahiruddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,9]]},"references-count":45,"alternative-id":["9927160","9927160"],"URL":"https:\/\/doi.org\/10.1155\/2024\/9927160","relation":{},"ISSN":["1741-4288","1741-427X"],"issn-type":[{"value":"1741-4288","type":"electronic"},{"value":"1741-427X","type":"print"}],"subject":[],"published":{"date-parts":[[2024,2,9]]}}}