{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:41Z","timestamp":1787029061993,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Foundation of China","award":["31930015\uff0c32070444 and 31801975"],"award-info":[{"award-number":["31930015\uff0c32070444 and 31801975"]}]},{"name":"Chinese Academy of Sciences","award":["XDB31000000\uff0c2018YFA0801403, SAJC202103 and K. C. Wong Education Foundation"],"award-info":[{"award-number":["XDB31000000\uff0c2018YFA0801403, SAJC202103 and K. C. Wong Education Foundation"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess antiplatelet activity and potential antithrombotic effect. Our study aims to elucidate the potential target of soy isoflavone in platelet. The anti-thrombosis formation effect of genistein and daidzein was evaluated in ex vivo perfusion chamber model under low (300 s\u22121) and high (1800 s\u22121) shear forces. The effect of genistein and daidzein on platelet aggregation and spreading was evaluated with platelets from both wildtype and GPIb\u03b1 deficient mice. The interaction of these soy isoflavone with 14-3-3\u03b6 was detected by surface plasmon resonance (SPR) and co-immunoprecipitation, and the effect of \u03b1IIb\u03b23-mediated outside-in signaling transduction was evaluated by western blot. We found both genistein and daidzein showed inhibitory effect on thrombosis formation in perfusion chamber, especially under high shear force (1800 s\u22121). These soy isoflavone interact with 14-3-3\u03b6 and inhibited both GPIb-IX and \u03b1IIb\u03b23-mediated platelet aggregation, integrin-mediated platelet spreading and outside-in signaling transduction. Our findings indicate that 14-3-3\u03b6 is a novel target of genistein and daidzein. 14-3-3\u03b6, an adaptor protein that regulates both GPIb-IX and \u03b1IIb\u03b23-mediated platelet activation is involved in soy isoflavone mediated platelet inhibition.<\/jats:p>","DOI":"10.3390\/molecules26164911","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T09:22:38Z","timestamp":1628846558000},"page":"4911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Soy Isoflavones Inhibit Both GPIb-IX Signaling and \u03b1IIb\u03b23 Outside-In Signaling via 14-3-3\u03b6 in Platelet"],"prefix":"10.3390","volume":"26","author":[{"given":"Ming","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-8503","authenticated-orcid":false,"given":"Gan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioactive Peptides, Yunnan Province\/Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runjia","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioactive Peptides, Yunnan Province\/Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanbin","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Department of Laboratory Medicine, LKSKI-Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Toronto, ON M5B 1W8, Canada"},{"name":"Toronto Platelet Immunobiology Group, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7621-2945","authenticated-orcid":false,"given":"Heyu","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Department of Laboratory Medicine, LKSKI-Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Toronto, ON M5B 1W8, Canada"},{"name":"Toronto Platelet Immunobiology Group, Toronto, ON M5B 1W8, Canada"},{"name":"Department of Physiology, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Canadian Blood Services Centre for Innovation, Toronto, ON M5G 2M1, Canada"},{"name":"Department of Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Lai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioactive Peptides, Yunnan Province\/Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/S0140-6736(16)31012-1","article-title":"Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: A systematic analysis for the Global Burden of Disease Study 2015","volume":"388","author":"Wang","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/nrcardio.2015.101","article-title":"MicroRNAs in platelet function and cardiovascular disease","volume":"12","author":"McManus","year":"2015","journal-title":"Nat. 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