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龙血调节与二硫化物化相关的基因以减轻小鼠缺血性脑损伤。

Dragon's Blood Modulates Disulfidptosis-Related Genes to Alleviate Ischemic Brain Injury in Mice.

作者信息

Xu Can, Hang Hang, Li Wanxian, Meng Yan, Zhao Heng, Liu Cuiying, Zhang Rongping

机构信息

College of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan University of Chinese Medicine, Kunming, 650500, China.

Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Joint Innovation Center for Brain Disorders, Ministry of Science and Technology, Capital Medical University, Beijing, China.

出版信息

Neurochem Res. 2025 Jun 6;50(3):185. doi: 10.1007/s11064-025-04428-5.

DOI:10.1007/s11064-025-04428-5
PMID:40478465
Abstract

Dragon's Blood (DB), a natural resin extracted from Dracaena cochinchinensis, exhibits anti-inflammatory and neuroprotective properties, but its efficacy and underlying mechanisms in ischemic stroke remain to be fully elucidated. In this study, the neuroprotective effects of DB were evaluated using both transient and permanent middle cerebral artery occlusion (tMCAO and dMCAO) models in mice. DB treatment significantly reduced infarct volume, improved neurological outcomes, and alleviated neuronal apoptosis. Transcriptomic profiling revealed that DB modulated signaling pathways related to neuroinflammation, blood-brain barrier (BBB) integrity, and actin cytoskeleton remodeling. These effects were supported by decreased Evans blue leakage, upregulated expression of tight junction proteins (ZO-1 and Claudin-5), and suppressed pro-inflammatory mediators including TNF-α, IL-1β, IL-6, and iNOS, along with increased levels of Arg-1 and IL-10. Moreover, DB downregulated disulfidptosis-related genes such as Flna, Iqgap1, Tln1, and Myh9. Molecular docking further suggested that Loureirin B, a major active constituent of DB, binds strongly to these targets, indicating a potential mechanistic link. These findings suggest that DB confers multi-target neurovascular protection in ischemic stroke by regulating inflammation, preserving BBB function, and inhibiting disulfidptosis, supporting its potential as a candidate for therapeutic development.

摘要

龙血(DB)是从柬埔寨龙血树中提取的一种天然树脂,具有抗炎和神经保护特性,但其在缺血性中风中的疗效和潜在机制仍有待充分阐明。在本研究中,使用小鼠短暂性和永久性大脑中动脉闭塞(tMCAO和dMCAO)模型评估了DB的神经保护作用。DB治疗显著减少了梗死体积,改善了神经功能结局,并减轻了神经元凋亡。转录组分析表明,DB调节了与神经炎症、血脑屏障(BBB)完整性和肌动蛋白细胞骨架重塑相关的信号通路。这些作用得到了伊文思蓝渗漏减少、紧密连接蛋白(ZO-1和Claudin-5)表达上调、包括TNF-α、IL-1β、IL-6和iNOS在内的促炎介质受到抑制以及Arg-1和IL-10水平升高的支持。此外,DB下调了与二硫键介导的细胞程序性坏死相关的基因,如Flna、Iqgap1、Tln1和Myh9。分子对接进一步表明,DB的主要活性成分龙血素B与这些靶点强烈结合,表明存在潜在的机制联系。这些发现表明,DB通过调节炎症、维持BBB功能和抑制二硫键介导的细胞程序性坏死,在缺血性中风中提供多靶点神经血管保护,支持其作为治疗开发候选药物的潜力。

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本文引用的文献

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Aging Dis. 2024 Dec 16. doi: 10.14336/AD.2024.1047.
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Corrigendum to "Drug pairs of Huangqi and Danggui alleviates pyroptosis by promoting autophagy activity via AMPK/mTOR signaling pathway in middle-cerebral artery occlusion/reperfusion in rats" [2024 Oct 23;337(Pt 3):118982].《黄芪与当归药对通过AMPK/mTOR信号通路促进自噬活性减轻大鼠大脑中动脉闭塞/再灌注后的细胞焦亡》勘误 [2024年10月23日;337(第3期):118982]
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Hypoxanthine is a metabolic biomarker for inducing GSDME-dependent pyroptosis of endothelial cells during ischemic stroke.
次黄嘌呤是一种代谢生物标志物,可在缺血性中风期间诱导内皮细胞中依赖 GSDME 的细胞焦亡。
Theranostics. 2024 Sep 16;14(15):6071-6087. doi: 10.7150/thno.100090. eCollection 2024.
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Endogenous defense mechanism-based neuroprotection in large-vessel acute ischemic stroke: A hope for future.基于内源性防御机制的大血管急性缺血性卒中神经保护:未来的希望
Brain Circ. 2024 Mar 21;10(1):51-59. doi: 10.4103/bc.bc_56_23. eCollection 2024 Jan-Mar.
5
Targeting PI3K/Akt in Cerebral Ischemia Reperfusion Injury Alleviation: From Signaling Networks to Targeted Therapy.靶向治疗脑缺血再灌注损伤中的 PI3K/Akt:从信号网络到靶向治疗。
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Identification of novel biomarkers and immune infiltration characteristics of ischemic stroke based on comprehensive bioinformatic analysis and machine learning.基于综合生物信息分析和机器学习的缺血性中风新型生物标志物及免疫浸润特征的鉴定
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