Yuan Xueying, Wang Hongrui, Zhao Zhicheng, Li Chuang, Wang Xingyuan, Liu Yu, Zhou Yulong, Zhu Zhanbo, Zhang Zecai
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.
Curr Microbiol. 2025 Feb 3;82(3):110. doi: 10.1007/s00284-025-04085-5.
The bovine herpesvirus type I (BHV-1) is a significant pathogen that poses a threat to the healthy development of the cattle industry and has a global prevalence. Paeonol is a phenolic constituent extracted from the dried root bark of peony in the buttercup family. Although paeonol has anti-inflammatory and antioxidant effects, its antiviral capacity remains unclear. Here, we conducted a cytotoxicity assay to screen the safe concentration of the paeonol using bovine turbinate (BT) cells as a model. Antiviral studies showed that paeonol inhibited BHV-1 gB gene and VP8 protein expression, and reduced cytopathic effect and viral titer. Furthermore, paeonol also demonstrated a potent effect on BHV-1 replication with an EC of 18.54 μg/mL and a Selectivity Index (SI) of 28.64. Mechanistic analysis revealed that the PI3K/AKT pathway might be involved in the antiviral mechanism of paeonol. Molecular docking combined with western blot assay further confirmed that paeonol was able to bind stably to the active sites of PI3K and AKT proteins, and significantly inhibited the activation of PI3K/AKT pathway. Interestingly, 740Y-P (a PI3K/AKT pathway agonist) significantly attenuated the anti-BHV-1 effect of paeonol. The above experiments are the first to confirm the inhibitory effect of paeonol on BHV-1 replication, which not only adds evidence to the biological function of paeonol as an antiviral agent, but also lays the foundation for the prevention and control of this disease and the development of feed additives.
牛疱疹病毒I型（BHV - 1）是一种对养牛业健康发展构成威胁的重要病原体，在全球广泛流行。丹皮酚是从毛茛科芍药属植物干燥根皮中提取的一种酚类成分。尽管丹皮酚具有抗炎和抗氧化作用，但其抗病毒能力仍不清楚。在此，我们进行了细胞毒性试验，以牛鼻甲（BT）细胞为模型筛选丹皮酚的安全浓度。抗病毒研究表明，丹皮酚抑制BHV - 1 gB基因和VP8蛋白表达，并降低细胞病变效应和病毒滴度。此外，丹皮酚对BHV - 1复制也有显著作用，其半数效应浓度（EC）为18.54μg/mL，选择性指数（SI）为28.64。机制分析显示，PI3K/AKT信号通路可能参与了丹皮酚的抗病毒机制。分子对接结合蛋白质免疫印迹分析进一步证实，丹皮酚能够与PI3K和AKT蛋白的活性位点稳定结合，并显著抑制PI3K/AKT信号通路的激活。有趣的是，740Y - P（一种PI3K/AKT信号通路激动剂）显著减弱了丹皮酚对BHV - 1的抗病毒作用。上述实验首次证实了丹皮酚对BHV - 1复制的抑制作用，这不仅为丹皮酚作为抗病毒剂的生物学功能增添了证据，也为该病的防控及饲料添加剂的开发奠定了基础。
