{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:01:15Z","timestamp":1792728075054,"version":"4.5.0"},"reference-count":48,"publisher":"Georg Thieme Verlag KG","issue":"08","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81603361"],"award-info":[{"award-number":["81603361"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"crossref","award":["ZR2022LZY021"],"award-info":[{"award-number":["ZR2022LZY021"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>\n            Background\u2003Vascular injury results in uncontrollable hemorrhage in hemorrhagic diseases and excessive antithrombotic therapy. Safe and efficient hemostatic agents which can be orally administered are urgently needed. Platelets play indispensable roles in hemostasis, but there is no drug exerting hemostatic effects through enhancing platelet function.<\/jats:p><jats:p>\n            Methods\u2003The regulatory effects of icaritin, a natural compound isolated from Herba Epimedii, on the dense granule release, thromboxane A2 (TxA2) synthesis, \u03b1-granule release, activation of integrin \u03b1IIb\u03b23, and aggregation of platelets induced by multiple agonists were investigated. The effects of icaritin on tail vein bleeding times of warfarin-treated mice were also evaluated. Furthermore, we investigated the underlying mechanisms by which icaritin exerted its pharmacological effects.<\/jats:p><jats:p>\n            Results\u2003Icaritin alone did not activate platelets, but significantly potentiated the dense granule release, \u03b1-granule release, activation of integrin \u03b1IIb\u03b23, and aggregation of platelets induced by thrombin and U46619. Icaritin also shortened tail vein bleeding times of mice treated with warfarin. In addition, phosphorylated proteome analysis, immunoblotting analysis, and pharmacological research revealed that icaritin sensitized the activation of phospholipase C\u03b32 (PLC\u03b32)-protein kinase C (PKC) signaling pathways, which play important roles in platelet activation.<\/jats:p><jats:p>\n            Conclusion\u2003Icaritin can sensitize platelet activation induced by thrombin and TxA2 through enhancing the activation of PLC\u03b32-PKC signaling pathways and promote hemostasis, and has potential to be developed into a novel orally deliverable therapeutic agent for hemorrhages.<\/jats:p>","DOI":"10.1055\/a-2245-8457","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:59:25Z","timestamp":1705366765000},"page":"753-769","source":"Crossref","is-referenced-by-count":6,"title":["Icaritin Sensitizes Thrombin- and TxA2-Induced Platelet Activation and Promotes Hemostasis via Enhancing PLC\u03b32-PKC Signaling Pathways"],"prefix":"10.1055","volume":"124","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7476-309X","authenticated-orcid":false,"given":"Zhixiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanggan","family":"Luo","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjing","family":"Liao","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Guo","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doudou","family":"Hao","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Lu","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjing","family":"Huang","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghong","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. 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Ltd., Linyi City, Shandong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Oncology and Cancer Therapeutics Program, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewu","family":"Zeng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Tu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guimin","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. 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