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Taxifolin is a natural dihydroflavonol compound with antioxidant properties. However, its mechanism of action on platelets and thrombosis remains unclear. Therefore, this study aimed to investigate the effects of taxifolin on platelet function and thrombus formation and identify its potential targets. The results revealed that taxifolin inhibited platelet aggregation induced by various agonists, such as ADP, collagen, thrombin, U46619, and convulxin. Moreover, it also limited platelet adhesion to collagen and the synthesis of TXA<jats:sub>2<\/jats:sub>. Additionally, it impeded platelet integrin \u03b1IIb\u03b23 \u2018\u2019outside\u2010in \u2018\u2019\u00a0signaling, which is crucial for stable clot formation. In animal models, taxifolin showed promising results in preventing pulmonary embolism and arterial thrombosis. More importantly, taxifolin did not cause significant side effects. Network pharmacology analysis suggested that taxifolin may exert its effects through key targets involved in platelet aggregation and thrombus formation, such as MAPK1, AKT1, SRC, PIK3R1, and MAPK8. Meanwhile, molecular docking studies confirmed the interaction between taxifolin and MAPK1. Furthermore, taxifolin inhibited the phosphorylation of ERK, p38, JNK, and Akt, key proteins in the MAPK and PI3K\/Akt signaling pathways. Overall, taxifolin demonstrated potential as an antiplatelet and antithrombotic agent, acting through multiple pathways and targets.<\/jats:p>","DOI":"10.1002\/mnfr.70129","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T05:20:28Z","timestamp":1752124828000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Taxifolin Inhibits Platelet Activation and Thrombosis by Regulating the PI3K\/Akt and MAPK Signaling Pathways"],"prefix":"10.1002","volume":"69","author":[{"given":"Fang","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Xiangyang Key Laboratory of Special Preparation of Vitiligo Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and Science  Xiangyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuqin","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoying","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Laboratory Animal &amp; Shandong Laboratory Animal Center Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanzhan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4804-1787","authenticated-orcid":false,"given":"Gang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Guizhou Medical University  Guiyang China"},{"name":"Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","first-page":"S281","article-title":"Platelet dysfunction after trauma: From mechanisms to targeted treatment","volume":"62","author":"Sloos P. 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