3-脱氧参查尔酮对Xa因子活性、血小板聚集和实验性血栓形成的抑制作用。

IF 3.6 3区 医学 Q2 CHEMISTRY, MEDICINAL
Jinhee Lee, Gyuri Han, Jong-Sup Bae
{"title":"3-脱氧参查尔酮对Xa因子活性、血小板聚集和实验性血栓形成的抑制作用。","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":"{\"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}","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

摘要

3-脱氧番木瓜查尔酮(3-DSC),从番木瓜中提取,被认为具有抗炎、抗流感和抗过敏作用,但其抗血栓特性尚未被研究。本研究探讨了3-DSC是否具有抗血栓作用,并探讨了其中的机制。通过各种方法评估3-DSC的抗血栓特性,包括凝血时间测试、血小板聚集分析、Xa因子活性和产生的评估、一氧化氮水平和相关蛋白的表达。本研究发现,3-DSC延长了人血小板缺乏血浆的凝血时间,其水平与标准抗凝剂利伐沙班相当,并降低了ADP或血栓素A2类似物U46619引发的血小板聚集。此外,3-DSC抑制了plc - γ - 2和PKC的磷酸化,以及细胞内钙的释放,这是血小板聚集所必需的。同时降低粘附分子p -选择素和PAC-1的表达。此外,在暴露于ADP或U46619的内皮细胞中,3-DSC促进一氧化氮的产生,同时减少内皮素-1的分泌。最后,它抑制内皮细胞中凝血因子Xa的活性和产生,并阻止激活因子X (FXa)诱导的血小板聚集。在血栓栓塞小鼠模型中,注射3-DSC可显著缩短血栓溶解所需时间,减少血栓大小和数量,降低死亡率。研究表明,与标准抗凝剂相比,3-DSC通过延长凝血时间、抑制血小板聚集和降低Xa因子活性,有效地表现出抗血栓活性。这些发现突出了3-DSC作为一种有前途的治疗药物的潜力,靶向血栓形成的多种途径,副作用更小。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inhibitory Effects of 3-Deoxysappanchalcone on Factor Xa Activity, Platelet Aggregation, and Experimentally Induced Thrombosis.

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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Archiv der Pharmazie
Archiv der Pharmazie 医学-化学综合
CiteScore
7.90
自引率
5.90%
发文量
176
审稿时长
3.0 months
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信