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木犀草素通过调节PI3K/AKT通路抑制牛疱疹病毒1型(BHV-1)复制并减轻病毒诱导的炎症反应。

Luteolin inhibits BHV-1 replication and alleviates virus-induced inflammatory responses by regulating PI3K/AKT pathway.

作者信息

Li Chuang, Zhao Zhicheng, Yuan Xueying, Wang Xingyuan, Wang Hongrui, Fan Jialin, Liu Yu, Zhou Yulong, Zhu Zhanbo, Zhang Zecai

机构信息

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, 163319, China; Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, Daqing, 163319, China; Engineering Research Center for Prevention and Control of Cattle Diseases, Heilongjiang Province, Daqing, 163319, China.

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, 163319, China.

出版信息

Microb Pathog. 2025 Feb;199:107258. doi: 10.1016/j.micpath.2024.107258. Epub 2024 Dec 24.

DOI:10.1016/j.micpath.2024.107258
PMID:39725044
Abstract

Bovine herpesvirus type 1 (BHV-1) seriously affects the production safety of the cattle industry and leads to epidemics worldwide. Luteolin (Lut), a flavonoid substance, can be found in vegetables, fruits, and herbs and possesses various biological properties. Here, we found that Lut can dose-dependently and significantly inhibit the cytopathic effects of BHV-1, decrease the viral titer, and suppress the BHV-1 gB gene and VP8 protein levels on bovine nasal turbinate osteoblasts (BT) and bovine kidney epithelial cells (MDBK). Mechanistic studies revealed that Lut can stably bind to the active sites of PI3K and AKT, and inhibit the PI3K/AKT pathway. Interestingly, 740Y-P (an agonist of the PI3K/AKT pathway) significantly attenuated the anti-BHV-1 effects of Lut. Further studies on the anti-inflammatory effects of Lut revealed that it attenuated BHV-1-induced activation of the NFκB pathway, which significantly suppressed the expression of TNF-α, IL-1β, IL-6, and IL-8 and increased the expression levels of IL-4 and IL-10. The PI3K/AKT pathway was also found to be involved in the anti-inflammatory effects of Lut. These results confirm the inhibitory effect of Lut on BHV-1 replication, which lays the foundation for further studies on the prevention and control of BHV-1.

摘要

牛疱疹病毒1型(BHV-1)严重影响养牛业的生产安全,并在全球范围内引发疫情。木犀草素(Lut)是一种类黄酮物质,存在于蔬菜、水果和草药中,具有多种生物学特性。在此,我们发现Lut能剂量依赖性且显著抑制BHV-1的细胞病变效应,降低病毒滴度,并抑制牛鼻甲成骨细胞(BT)和牛肾上皮细胞(MDBK)上BHV-1 gB基因和VP8蛋白水平。机制研究表明,Lut能稳定结合PI3K和AKT的活性位点,并抑制PI3K/AKT通路。有趣的是,740Y-P(PI3K/AKT通路的激动剂)显著减弱了Lut的抗BHV-1作用。对Lut抗炎作用的进一步研究表明,它减弱了BHV-1诱导的NFκB通路激活,这显著抑制了TNF-α、IL-1β、IL-6和IL-8的表达,并增加了IL-4和IL-10的表达水平。还发现PI3K/AKT通路参与了Lut的抗炎作用。这些结果证实了Lut对BHV-1复制的抑制作用,为进一步研究BHV-1的防控奠定了基础。

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