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（左）PAS840提取物通过抑制炎性小体激活促进缺血性中风恢复。

(L.) Extract PAS840 Promotes Ischemic Stroke Recovery by Inhibiting Inflammasome Activation.

作者信息

Yang Xin, Hong Canhui, Guan Tangfei, Zhang Chenggui, Yang Yongshou, Xiao Peiyun, Xiao Huai, He Zhengchun

机构信息

Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali 671000, China.

National-Local Joint Engineering Research Center of Entomoceutics, Dali 671000, China.

出版信息

Biology (Basel). 2025 May 22;14(6):589. doi: 10.3390/biology14060589.

DOI:10.3390/biology14060589
PMID:40563841
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12189569/
Abstract

Ischemic stroke (IS) is a high-mortality, multi-complication cardiovascular disease. Reducing brain injury and promoting neuronal repair after IS onset remain important challenges for current treatments. Our team previously found that PAS840, an extract from (L.), protects nerve function; this study further uses LC-MS/MS and peptidomics to analyze PAS840's components and network pharmacology to predict its ischemic stroke (IS) therapeutic targets. We then employed Transwell, a biochemical kit, real-time quantitative polymerase chain reaction (RT-qPCR), and transcriptomics to investigate PAS840's effects on migration ability, oxidative stress levels, and cellular pathways in mouse microglial cells (BV-2) following oxygen-glucose deprivation/reoxygenation (OGD/R) injury. Finally, using Evans blue staining, immunohistochemical analysis, and RT-qPCR, we investigated PAS840's effects on the blood-brain barrier, inflammation pathways, and neural function in a transient middle cerebral artery occlusion (tMCAO) rat model. PAS840 components target multiple IS pathways, effectively inhibit NF-κB/NLRP3/Caspase-1/IL-1β inflammasome pathway activation in BV-2 cells following OGD/R, reduce cellular oxidative stress, inflammation, and pyroptosis, and improve cell viability and migration ability. PAS840 decreases NF-κB/NLRP3/Caspase-1/IL-1β inflammasome pathway expression in tMCAO rat brains, reduces inflammation, activates BDNF/VGF/NGR1/Erbb4 neurotrophic factor and vascular endothelial growth factor pathways, enhances neuronal cell viability, and effectively protects and repairs the blood-brain barrier.

摘要

缺血性中风（IS）是一种高死亡率、多并发症的心血管疾病。减少IS发病后的脑损伤并促进神经元修复仍然是当前治疗面临的重要挑战。我们的团队之前发现，来自[植物名称]的提取物PAS840可保护神经功能；本研究进一步使用液相色谱-串联质谱（LC-MS/MS）和肽组学分析PAS840的成分，并利用网络药理学预测其缺血性中风（IS）的治疗靶点。然后，我们采用Transwell、生化试剂盒、实时定量聚合酶链反应（RT-qPCR）和转录组学，研究PAS840对氧糖剥夺/复氧（OGD/R）损伤后小鼠小胶质细胞（BV-2）迁移能力、氧化应激水平和细胞通路的影响。最后，我们使用伊文思蓝染色、免疫组织化学分析和RT-qPCR，研究PAS840对短暂性大脑中动脉闭塞（tMCAO）大鼠模型血脑屏障、炎症通路和神经功能的影响。PAS840成分靶向多个IS通路，有效抑制OGD/R后BV-2细胞中NF-κB/NLRP3/Caspase-1/IL-1β炎性小体通路的激活，降低细胞氧化应激、炎症和焦亡，提高细胞活力和迁移能力。PAS840降低tMCAO大鼠脑中NF-κB/NLRP3/Caspase-1/IL-1β炎性小体通路的表达，减轻炎症，激活BDNF/VGF/NGR1/Erbb4神经营养因子和血管内皮生长因子通路，增强神经元细胞活力，并有效保护和修复血脑屏障。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e99b/12189569/92fc37d6f48e/biology-14-00589-g014.jpg
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本文引用的文献

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Extract Protects Glutamate-Induced Nerve Cell Damage by Inhibiting Receptor Activation.提取物通过抑制受体激活来保护谷氨酸诱导的神经细胞损伤。
Biology (Basel). 2025 Feb 13;14(2):193. doi: 10.3390/biology14020193.
2
Investigation of the effects of (L.) extract on ischemic stroke based on combined multi-omics of gut microbiota.基于肠道微生物群联合多组学研究（L.）提取物对缺血性中风的影响。
Front Pharmacol. 2024 Nov 28;15:1429960. doi: 10.3389/fphar.2024.1429960. eCollection 2024.
3
Comprehensive Management of Stroke: From Mechanisms to Therapeutic Approaches.
脑卒中的综合管理：从机制到治疗方法。
Int J Mol Sci. 2024 May 11;25(10):5252. doi: 10.3390/ijms25105252.
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Not open and shut: Complex and prolonged blood-brain barrier responses after stroke.并非一目了然：中风后复杂且持久的血脑屏障反应。
J Cereb Blood Flow Metab. 2024 Mar;44(3):446-448. doi: 10.1177/0271678X231216153. Epub 2023 Nov 24.
5
Periplaneta Americana (L.) extract activates the ERK/CREB/BDNF pathway to promote post-stroke neuroregeneration and recovery of neurological functions in rats.美洲大蠊（L.）提取物通过激活 ERK/CREB/BDNF 通路促进大鼠卒中后神经再生和神经功能恢复。
J Ethnopharmacol. 2024 Mar 1;321:117400. doi: 10.1016/j.jep.2023.117400. Epub 2023 Nov 11.
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Stroke-induced damage on the blood-brain barrier.中风引起的血脑屏障损伤。
Front Neurol. 2023 Sep 28;14:1248970. doi: 10.3389/fneur.2023.1248970. eCollection 2023.
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N-acetyldopamine oligomers from Periplaneta americana with anti-inflammatory and vasorelaxant effects and their spatial distribution visualized by mass spectrometry imaging.美洲大蠊来源的 N-乙酰多巴胺低聚物具有抗炎和血管舒张作用，并通过质谱成像可视化其空间分布。
J Ethnopharmacol. 2024 Jan 10;318(Pt B):116989. doi: 10.1016/j.jep.2023.116989. Epub 2023 Jul 31.
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DTX3L induced NLRP3 ubiquitination inhibit R28 cell pyroptosis in OGD/R injury.DTX3L 诱导 NLRP3 泛素化抑制 OGD/R 损伤中 R28 细胞焦亡。
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Periplaneta americana (Insecta: Blattodea) and organ fibrosis: A mini review.美洲大蠊（昆虫纲：蜚蠊目）与器官纤维化：小型综述。
Medicine (Baltimore). 2022 Dec 23;101(51):e32039. doi: 10.1097/MD.0000000000032039.
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extract alleviates steatohepatitis in a mouse model by modulating HMGB1-mediated inflammatory response.提取物通过调节HMGB1介导的炎症反应减轻小鼠模型中的脂肪性肝炎。
Front Pharmacol. 2022 Oct 3;13:995523. doi: 10.3389/fphar.2022.995523. eCollection 2022.