DataSheet_1_Chrysin Ameliorates Influenza Virus Infection in the Upper Airways by Repressing Virus-Induced Cell Cycle Arrest and Mitochondria-Dependent Apoptosis.pdf

Chrysin has been proven to possess antiviral properties, but the precise underlying anti-influenza mechanism and its anti-influenza efficacy in vivo are largely unclear. In this study, we investigated the involvement of chrysin in the blockade of cell cycle and apoptosis in distinct cell lines subjected to two H1N1 influenza A virus (IAV) strains, as well as its anti-IAV activity in vivo. Here, we found an early unidentified finding that chrysin strongly impeded IAV replication through a mechanism that was autonomous of innate antiviral immune activation and viral protein interaction. Surprisingly, chrysin can suppress IAV-induced cell cycle arrest in the G0/G1 phase by downregulating the expression levels of P53 and P21 while promoting Cyclin D1/CDK4 and Cyclin E1/CDK2 activation. Furthermore, chrysin dramatically inhibited the IAV-triggered mitochondrial apoptotic pathway by altering the balance of Bax/Bcl-xl and reducing caspase-9 and caspase-3 activation. Accumulated reactive oxygen species (ROS) reduction may contribute to the inhibitory role of chrysin in cell cycle arrest and apoptosis following IAV infection. Notably, chrysin preferably inhibited IAV replication in the upper respiratory tract, indicating that it might be a promising drug for restraining the spread of respiratory viruses.

白杨素（Chrysin）已被证实具备抗病毒活性，但其抗流感的确切潜在分子机制以及体内抗流感功效仍尚不明确。本研究针对两株H1N1亚型甲型流感病毒（Influenza A virus, IAV）感染的不同细胞系，探究了白杨素对细胞周期阻滞与病毒诱导细胞凋亡的干预作用，并验证了其体内抗甲型流感病毒活性。本研究首次发现，白杨素可通过不依赖先天抗病毒免疫激活与病毒蛋白互作的机制，强效抑制甲型流感病毒复制。令人意外的是，白杨素可通过下调P53与P21的表达水平，同时促进Cyclin D1/CDK4及Cyclin E1/CDK2通路激活，从而抑制甲型流感病毒诱导的G0/G1期细胞周期阻滞。此外，白杨素可通过改变Bax/Bcl-xl的蛋白平衡，降低caspase-9与caspase-3的激活水平，显著抑制甲型流感病毒诱发的线粒体凋亡通路。甲型流感病毒感染后活性氧（reactive oxygen species, ROS）的积累减少，可能是白杨素发挥细胞周期阻滞与细胞凋亡抑制作用的重要机制。值得注意的是，白杨素可优先抑制甲型流感病毒在上呼吸道的复制，提示其有望成为遏制呼吸道病毒传播的潜在候选药物。