灯盏花素注射液及其主要成分灯盏花素通过抑制新生小鼠神经炎症和氧化应激来预防致死性肠病毒感染

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-07-06 DOI:10.1016/j.phymed.2025.157042

Wenhui Yang , Junyi Wang , Yi Tao , Xiaodi Li , Shanbo Tao , Huilin Zhu , Xi Chen , Jinjun Shan , Yongming Li , Tonghui Ma , Peng Cao , Guangyi Cui

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引用次数: 0

摘要

背景肠病毒71型（EV71）是儿童手足口病（HFMD）相关的严重神经系统感染的主要原因，目前尚无专门的治疗药物。灯盏花素注射液因其对缺血性脑卒中的神经保护作用而在国内得到广泛应用。目的探讨BRE注射液及其主要成分黄芩苷预防新生小鼠EV71致死性感染的作用及机制。方法建立新生小鼠EV71致死性感染模型，评价BRE注射液及其主要成分黄芩苷的治疗效果。采用ev71感染细胞培养模型分析其抗病毒作用。利用分子生物学和组织化学技术探讨其潜在机制。结果黄芩苷注射液及其主要成分黄芩苷（SCU,≥99%）对新生小鼠EV71型致死性感染具有保护作用。EV71感染主要发生在脑干外周区域，星形胶质细胞是最常见的感染细胞类型，小胶质细胞感染率最高。SCU对不同类型胶质细胞的EC50值在4.11 ~ 6.62 μM之间。它通过调节kelch样ECH相关蛋白1/核因子-红系2-相关因子2 （Keap1/Nrf2）和RELA原癌基因、NF-kB亚基/NLR家族pyrin结构域3 （P65/NLRP3）通路抑制EV71复制，减轻氧化应激，减轻神经炎症。结论BRE注射液scu通过抑制病毒复制、减少氧化损伤和神经炎症，保护新生小鼠免受EV71致命感染。其潜在机制涉及脑干胶质细胞中Keap1/Nrf2通路的增强和P65/NLRP3通路的抑制。

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Breviscapine injection and its main component scutellarin prevents lethal enterovirus infection by inhibiting neuroinflammation and oxidative stress in newborn mice

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Breviscapine injection and its main component scutellarin prevents lethal enterovirus infection by inhibiting neuroinflammation and oxidative stress in newborn mice

Background

Enterovirus 71 (EV71) is the primary cause of severe neurological infections associated with Hand, Foot and Mouth Disease (HFMD) in children, and no specific therapeutic agent is available. Breviscapine injection (BRE Injection) is widely used in China for its neuroprotective properties in ischemic stroke.

Objective

To investigate the therapeutic impact and mechanisms of BRE Injection and its main component scutellarin in preventing fatal infection of EV71 in newborn mice.

Methods

A fatal EV71 infection model in newborn mice was developed to evaluate the effectiveness of BRE Injection and its main component scutellarin. The antiviral effects were analyzed using EV71-infected cell culture models. Molecular biology and histochemistry techniques were used to explore the underlying mechanisms.

Results

BRE Injection and its principal component, scutellarin (SCU, ≥99 %), successfully safeguarded newborn mice against fatal EV71 infection. EV71 infection predominantly occurred in the peripheral regions of the brainstem in the brain, with astrocytes being the most commonly infected cell type, and microglia showing the highest infection rate. SCU demonstrated antiviral activity with EC₅₀ values between 4.11 and 6.62 μM across different glial cells types. It inhibits EV71 replication, mitigates oxidative stress, reduces neuroinflammation by modulating the Kelch-like ECH Associated Protein 1/Nuclear Factor erythroid 2-Related Factor 2 (Keap1/Nrf2) and RELA proto-oncogene, NF-kB subunit/NLR family pyrin domain containing 3 (P65/NLRP3) pathways.

Conclusion

SCU from BRE Injection safeguarded newborn mice against fatal EV71 infection by inhibiting viral replication, and reducing oxidative damage and neuroinflammation. The underlying mechanisms involve enhancement of Keap1/Nrf2 pathway and inhibition of P65/NLRP3 pathway in glial cells of the brainstem.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.