{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T19:08:57Z","timestamp":1784056137444,"version":"3.55.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82575126"],"award-info":[{"award-number":["82575126"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20416"],"award-info":[{"award-number":["U23A20416"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82474460"],"award-info":[{"award-number":["82474460"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"State Key Laboratory of New Targets and Drug Development for Major Diseases","award":["SKLD2024Q08"],"award-info":[{"award-number":["SKLD2024Q08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Shikonin, a major bioactive naphthoquinone derived from Lithospermum erythrorhizon, exhibits broad pharmacological properties. However, its effects on platelet activation and arterial thrombosis, as well as the underlying mechanisms, remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated network pharmacology with comprehensive in vitro and in vivo assays. Human platelets were utilized to evaluate aggregation, dense granule release, spreading, and clot retraction following shikonin treatment. Arterial thrombosis and hemostasis were assessed in vivo via murine FeCl3-induced mesenteric injury and tail bleeding models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>Network pharmacology analysis suggested that PI3K\/Akt-related signaling may be involved in the antithrombotic effects of shikonin. In vivo, shikonin prolonged tail bleeding time and impaired arterial thrombus formation, markedly decreasing thrombus stability and triggering the continuous shedding of unstable emboli. In vitro, shikonin inhibited thrombin- and collagen-induced platelet aggregation, granule secretion, spreading, and clot retraction. Mechanistically, shikonin reduced the phosphorylation of Akt and ERK.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Shikonin exerts potent antiplatelet and antithrombotic effects, which are associated with the suppression of Akt and ERK phosphorylation. These findings highlight shikonin as a promising candidate for further preclinical investigation as a novel antithrombotic therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgag070","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:45:13Z","timestamp":1784054713000},"source":"Crossref","is-referenced-by-count":0,"title":["Shikonin attenuates platelet activation and thrombosis: a pharmacological evaluation"],"prefix":"10.1093","volume":"78","author":[{"given":"Junfeng","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, School of Basic Medical Sciences, Zhejiang Chinese Medical University , Hangzhou , 310051,","place":["China"]},{"name":"Yangpu Hospital, School of Medicine, Tongji University , Shanghai , 200090,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaonan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, School of Basic Medical Sciences, Zhejiang Chinese Medical University , Hangzhou , 310051,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"She","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, Shanghai Children\u2019s Medical Center, Shanghai Jiao Tong University School of Medicine , Shanghai , 200127,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghao","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, School of Basic Medical Sciences, Zhejiang Chinese Medical University , Hangzhou , 310051,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingke","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, Zhejiang University School of Medicine , Hangzhou , 310058,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, School of Basic Medical Sciences, Zhejiang Chinese Medical University , Hangzhou , 310051,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, School of Basic Medical Sciences, Zhejiang Chinese Medical University , Hangzhou , 310051,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, Zhejiang University School of Medicine , Hangzhou , 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