Marine-Fungus-Derived Natural Compound 4-Hydroxyphenylacetic Acid Induces Autophagy to Exert Antithrombotic Effects in Zebrafish.

海洋真菌来源的天然化合物 4 - 羟基苯乙酸诱导自噬以释放斑马鱼的抗血栓形成作用。

• 影响指数: 6.085
• 发表时间: 2024 Mar 27
• 来源期刊: Mar Drugs
• DOI: 10.3390/md22040148
• PMID: 38667765
• 文章类型: Journal Article
• 中科院分区: Q1
• 方向: 医学
• 作者列表: Xin S,Zhang M,Li P,Wang L,Zhang X,Zhang S,Mu Z,Lin H,Li X,Liu K

关键词: 4-hydroxyphenylacetic acid; antithrombotic; autophagy; marine-derived fungus

Mesh: Animals; Zebrafish; Phenylacetates / pharmacology; Autophagy / drug effects; Fibrinolytic Agents / pharmacology; Signal Transduction / drug effects; Biological Products / pharmacology; Thrombosis / drug therapy; Disease Models, Animal; Aquatic Organisms

Abstract

Marine natural products are important sources of novel drugs. In this study, we isolated 4-hydroxyphenylacetic acid (HPA) from the marine-derived fungus Emericellopsis maritima Y39-2. The antithrombotic activity and mechanism of HPA were reported for the first time. Using a zebrafish model, we found that HPA had a strong antithrombotic activity because it can significantly increase cardiac erythrocytes, blood flow velocity, and heart rate, reduce caudal thrombus, and reverse the inflammatory response caused by Arachidonic Acid (AA). Further transcriptome analysis and qRT-PCR validation demonstrated that HPA may regulate autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway to exert antithrombotic effects.

摘要

海洋天然产物是新药的重要来源。在这项研究中,我们从海洋真菌EmericellopsismaritimaY39-2中分离出4-羟基苯乙酸（HPA）。首次报道了HPA的抗血栓活性和机制。使用斑马鱼模型，我们发现HPA具有很强的抗血栓活性，因为它可以显着增加心脏红细胞，血流速度,和心率,减少尾部血栓，逆转花生四烯酸（AA）引起的炎症反应。进一步的转录组分析和qRT-PCR验证表明，HPA可能通过抑制PI3K/AKT/mTOR信号通路来调节自噬，从而发挥抗血栓作用。