{"title":"Inhibitory Effects of 3-Deoxysappanchalcone on Factor Xa Activity, Platelet Aggregation, and Experimentally Induced Thrombosis.","authors":"Jinhee Lee, Gyuri Han, Jong-Sup Bae","doi":"10.1002/ardp.70101","DOIUrl":null,"url":null,"abstract":"<p><p>3-Deoxysappanchalcone (3-DSC), extracted from Caesalpinia sappan L., is recognized for its anti-inflammatory, anti-influenza, and anti-allergic effects, but its antithrombotic properties have not been investigated. This study explores whether 3-DSC exhibits antithrombotic effects and examines the mechanisms involved. The antithrombotic properties of 3-DSC were assessed through various methods, including tests for clotting times, platelet aggregation analysis, evaluation of factor Xa activity and production, nitric oxide levels, and the expression of related proteins. This study found that 3-DSC extended the clotting time in human platelet-poor plasma at levels comparable to rivaroxaban, a standard anticoagulant, and reduced platelet aggregation triggered by ADP or the thromboxane A2 analog U46619. Additionally, 3-DSC suppressed the phosphorylation of PLCγ2 and PKC, as well as intracellular calcium release, which are essential for platelet aggregation. It also decreased the expression of adhesion molecules P-selectin and PAC-1. Furthermore, 3-DSC promoted nitric oxide production while reducing endothelin-1 secretion in endothelial cells exposed to ADP or U46619. Lastly, it inhibited both the activity and production of coagulation factor Xa in endothelial cells and prevented activated factor X (FXa)-induced platelet aggregation. Injection of 3-DSC significantly shortened the time required for thrombus resolution, reduced the size and number of thrombi, and decreased mortality in mouse models of thromboembolism. The study demonstrates that 3-DSC effectively exhibits antithrombotic activity by prolonging the clotting time, inhibiting platelet aggregation, and reducing factor Xa activity, comparable to standard anticoagulants. These findings highlight the potential of 3-DSC as a promising therapeutic agent targeting multiple pathways involved in thrombosis, with reduced side effects.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 10","pages":"e70101"},"PeriodicalIF":3.6000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archiv der Pharmazie","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/ardp.70101","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
3-Deoxysappanchalcone (3-DSC), extracted from Caesalpinia sappan L., is recognized for its anti-inflammatory, anti-influenza, and anti-allergic effects, but its antithrombotic properties have not been investigated. This study explores whether 3-DSC exhibits antithrombotic effects and examines the mechanisms involved. The antithrombotic properties of 3-DSC were assessed through various methods, including tests for clotting times, platelet aggregation analysis, evaluation of factor Xa activity and production, nitric oxide levels, and the expression of related proteins. This study found that 3-DSC extended the clotting time in human platelet-poor plasma at levels comparable to rivaroxaban, a standard anticoagulant, and reduced platelet aggregation triggered by ADP or the thromboxane A2 analog U46619. Additionally, 3-DSC suppressed the phosphorylation of PLCγ2 and PKC, as well as intracellular calcium release, which are essential for platelet aggregation. It also decreased the expression of adhesion molecules P-selectin and PAC-1. Furthermore, 3-DSC promoted nitric oxide production while reducing endothelin-1 secretion in endothelial cells exposed to ADP or U46619. Lastly, it inhibited both the activity and production of coagulation factor Xa in endothelial cells and prevented activated factor X (FXa)-induced platelet aggregation. Injection of 3-DSC significantly shortened the time required for thrombus resolution, reduced the size and number of thrombi, and decreased mortality in mouse models of thromboembolism. The study demonstrates that 3-DSC effectively exhibits antithrombotic activity by prolonging the clotting time, inhibiting platelet aggregation, and reducing factor Xa activity, comparable to standard anticoagulants. These findings highlight the potential of 3-DSC as a promising therapeutic agent targeting multiple pathways involved in thrombosis, with reduced side effects.
期刊介绍:
Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.