School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China.
Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Viruses. 2023 Jul 8;15(7):1524. doi: 10.3390/v15071524.
The dual strategy of inhibiting the viral life cycle and reducing the host inflammatory response should be considered in the development of therapeutic drugs for influenza A virus (IAV). In this study, an extract of (SBE) containing seven flavonoids was identified to exert both antiviral and anti-inflammatory effects in macrophages infected with IAV. We performed transcriptome analysis using high-throughput RNA sequencing and identified 315 genes whose transcription levels were increased after IAV infection but were able to be decreased after SBE intervention. Combined with Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, these genes were mainly involved in TLR3/7/8, RIG-I/MDA5, NLRP3 and cGAS pattern recognition receptor (PRR)-mediated signaling pathways. SBE inhibited the transcription of essential genes in the above pathways and nuclear translocation of NF-κB p65 as confirmed by RT-qPCR and immunofluorescence, respectively, indicating that SBE reversed PR8-induced over-activation of the PRR signaling pathway and inflammation in macrophages. This study provides an experimental basis for applying and its main effects in the clinical treatment of viral pneumonia. It also provides novel targets for screening and developing novel drugs to prevent and treat IAV infectious diseases.
在开发抗甲型流感病毒 (IAV) 的治疗药物时,应考虑抑制病毒生命周期和减少宿主炎症反应的双重策略。本研究鉴定出含有七种类黄酮的 (SBE) 提取物,可在感染 IAV 的巨噬细胞中发挥抗病毒和抗炎作用。我们使用高通量 RNA 测序进行转录组分析,发现 315 个基因的转录水平在 IAV 感染后增加,但在 SBE 干预后能够降低。结合基因本体论 (GO) 和京都基因与基因组百科全书 (KEGG) 富集分析,这些基因主要参与 TLR3/7/8、RIG-I/MDA5、NLRP3 和 cGAS 模式识别受体 (PRR) 介导的信号通路。SBE 通过 RT-qPCR 和免疫荧光分别抑制了上述通路中必需基因的转录和 NF-κB p65 的核易位,表明 SBE 逆转了 PR8 诱导的 PRR 信号通路和巨噬细胞炎症的过度激活。本研究为应用 和其主要作用在病毒性肺炎的临床治疗提供了实验依据。它还为筛选和开发预防和治疗 IAV 传染病的新型药物提供了新的靶点。