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靶向中性粒细胞细胞外陷阱:来自传统中药的有前景的抗血栓治疗天然产物。

Targeting neutrophils extracellular traps, a promising anti-thrombotic therapy for natural products from traditional Chinese herbal medicine.

机构信息

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine,10 Poyanghu Road, Jinghai District, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

School of Management, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

出版信息

Biomed Pharmacother. 2024 Oct;179:117310. doi: 10.1016/j.biopha.2024.117310. Epub 2024 Sep 2.

DOI:10.1016/j.biopha.2024.117310
PMID:39226727
Abstract

Thrombi are the main cause of vascular occlusion and contribute significantly to cardiovascular events and death. Neutrophils extracellular traps (NETs)-induced thrombosis plays a vital role in thrombotic complications and it takes the main responsibility for the resistance of fibrinolysis. However, the conventional anti-thrombotic therapies are inadequate to treat NETs-induced thrombotic complications but carry a high risk of bleeding. Consequently, increased attention has shifted towards exploring novel anti-thrombotic treatments targeting NETs. Interestingly, accumulating evidences prove that natural products from traditional Chinese herbal medicines have a great potential to mitigate thrombosis through inhibiting generous NETs formation and degrading excessive NETs. In this review, we elaborated the formation and degradation of NETs and highlighted its pivotal role in immunothrombosis through interactions with platelets and coagulation factors. Since available anti-thrombotic drugs targeting NETs are deficient, we further summarized the natural products and compounds from traditional Chinese herbal medicines which exert effective actions on regulating NETs formation and also have anti-thrombotic effects. Our findings underscore the diverse effects of natural products in targeting NETs, including relieving inflammation and oxidative stress of neutrophils, inhibiting neutrophils activation and DNA efflux, suppressing granule proteins release, reducing histones and promoting DNA degradation. This review aims to highlight the significance of natural medicines in anti-thrombotic therapies through targeting NETs and to lay a groundwork for developing novel anti-thrombotic agents from traditional Chinese herbal medicines.

摘要

血栓是血管阻塞的主要原因,对心血管事件和死亡有重大影响。中性粒细胞胞外诱捕网(NETs)诱导的血栓形成在血栓并发症中起着至关重要的作用,它对纤维蛋白溶解的抵抗负有主要责任。然而,传统的抗血栓治疗不足以治疗 NETs 诱导的血栓并发症,但有很高的出血风险。因此,人们越来越关注探索针对 NETs 的新型抗血栓治疗方法。有趣的是,越来越多的证据证明,来自中药的天然产物通过抑制大量 NETs 的形成和降解过多的 NETs,具有减轻血栓形成的巨大潜力。在这篇综述中,我们详细阐述了 NETs 的形成和降解,并强调了它通过与血小板和凝血因子相互作用在免疫血栓形成中的关键作用。由于针对 NETs 的现有抗血栓药物不足,我们进一步总结了中药中的天然产物和化合物,它们在调节 NETs 形成方面具有有效作用,同时也具有抗血栓作用。我们的研究结果强调了天然产物在针对 NETs 方面的多种作用,包括缓解中性粒细胞的炎症和氧化应激,抑制中性粒细胞的激活和 DNA 外排,抑制颗粒蛋白的释放,减少组蛋白和促进 DNA 降解。本综述旨在强调通过针对 NETs 利用天然药物进行抗血栓治疗的重要性,并为开发中药新型抗血栓药物奠定基础。

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