Brevianamide F Exerts Antithrombotic Effects by Modulating the MAPK Signaling Pathway and Coagulation Cascade.

IF 4.9 2区医学 Q1 CHEMISTRY, MEDICINAL

Marine Drugs Pub Date : 2024-09-26 DOI:10.3390/md22100439

Huiwen Zhang, Chen Sun, Qing Xia, Peihai Li, Kechun Liu, Yun Zhang

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引用次数: 0

Abstract

Existing antithrombotic drugs have side effects such as bleeding, and there is an urgent need to discover antithrombotic drugs with better efficacy and fewer side effects. In this study, a zebrafish thrombosis model was used to evaluate the antithrombotic activity and mechanism of Brevianamide F, a deep-sea natural product, with transcriptome sequencing analysis, RT-qPCR analysis, and molecular docking. The results revealed that Brevianamide F significantly attenuated the degree of platelet aggregation in the thrombus model zebrafish, leading to an increase in the number of circulating platelets, an augmentation in the return of blood to the heart, an elevated heart rate, and a significant restoration of caudal blood flow velocity. Transcriptome sequencing and RT-qPCR validation revealed that Brevianamide F may exert antithrombotic effects through the modulation of the MAPK signaling pathway and the coagulation cascade reaction. Molecular docking analysis further confirmed this result. This study provides a reference for the development of therapeutic drugs for thrombosis.

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布雷维那酰胺 F 通过调节 MAPK 信号通路和凝血级联发挥抗血栓作用

现有的抗血栓药物都有出血等副作用，因此迫切需要发现疗效更好、副作用更小的抗血栓药物。本研究利用斑马鱼血栓模型，通过转录组测序分析、RT-qPCR分析和分子对接，评估了深海天然产物Brevianamide F的抗血栓活性和机制。结果表明，布雷维那酰胺 F 能显著减轻血栓模型斑马鱼的血小板聚集程度，导致循环血小板数量增加、心脏血液回流加快、心率上升以及尾部血流速度明显恢复。转录组测序和 RT-qPCR 验证表明，布雷维那酰胺 F 可通过调节 MAPK 信号通路和凝血级联反应发挥抗血栓作用。分子对接分析进一步证实了这一结果。这项研究为血栓治疗药物的开发提供了参考。

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来源期刊

Marine Drugs 医学-医药化学

CiteScore

9.60

自引率

14.80%

发文量

671

审稿时长

1 months

期刊介绍： Marine Drugs (ISSN 1660-3397) publishes reviews, regular research papers and short notes on the research, development and production of drugs from the sea. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible, particularly synthetic procedures and characterization information for bioactive compounds. There is no restriction on the length of the experimental section.