Andrographolide exerts anti-respiratory syncytial virus activity by up-regulating heme oxygenase-1 independent of interferon responses in human airway epithelial cells

作者全名："Che, Siyi; Zhou, Na; Liu, Ying; Xie, Jun; Liu, Enmei"

作者地址："[Che, Siyi; Zhou, Na; Xie, Jun; Liu, Enmei] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Resp Med, Minist Educ,Key Lab Child Dev & Disorders,Children, Chongqing 400014, Peoples R China; [Liu, Ying] Jiangxi Qingfeng Pharmaceut Co Ltd, State Key Lab Innovat Nat Med & TCM Inject, Ganzhou 341000, Peoples R China"

通信作者："Xie, J; Liu, EM (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Resp Med, Minist Educ,Key Lab Child Dev & Disorders,Children, Chongqing 400014, Peoples R China."

来源：MOLECULAR BIOLOGY REPORTS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000949717700002

JCR分区：Q4

影响因子：2.8

年份：2023

卷号：50

期号：5

开始页：4261

结束页：4272

文献类型：Article

关键词：Andrographolide; Respiratory syncytial virus; Heme oxygenase-1; Antivirus

摘要："BackgroundRespiratory syncytial virus (RSV) is the leading cause of mortality and morbidity in children under the age of five. Despite this, there is still a lack of safe and effective vaccines and antiviral agents for clinical use. Andrographolide exerts antiviral functions against a variety of viruses, but whether (and how) it exerts antiviral effects on RSV remains unclear.Methods and resultsIn vitro RSV infection models using A549 and 16HBE cell lines were established, and the effects of andrographolide on RSV were analyzed via RSV N gene load and proinflammatory cytokine levels. The RNA transcriptome was sequenced, and data were analyzed by R software. Andrographolide-related target genes were extracted via network pharmacology using online databases. Lentiviral transfection was applied to knockdown the heme oxygenase-1 gene (Hmox1, HO-1). Results showed that andrographolide suppressed RSV replication and attenuated subsequent inflammation. Network pharmacology and RNA sequencing analysis indicated that the hub gene HO-1 may play a pivotal role in the anti-RSV effects of andrographolide. Furthermore, andrographolide exerted antiviral effects against RSV partially by inducing HO-1 but did not activate the antiviral interferon response.ConclusionOur findings demonstrated that andrographolide exerted anti-RSV activity by up-regulating HO-1 expression in human airway epithelial cells, providing novel insights into potential therapeutic targets and drug repurposing in RSV infection."

基金机构：Open Project of the State Key Laboratory of Innovative Natural Medicine and TCM Injections [QFSKL2020020]; Leading Talents Project of Chongqing

基金资助正文：This research was funded by the Open Project of the State Key Laboratory of Innovative Natural Medicine and TCM Injections (QFSKL2020020) and Leading Talents Project of Chongqing.