Cirsimaritin inhibits influenza A virus replication by downregulating the NF-κB signal transduction pathway

Virol J. 2018 May 21;15(1):88. doi: 10.1186/s12985-018-0995-6.

Abstract

Background: Artemisia scoparia Waldst and Kit is a famous traditional Chinese medicine widely distributed in Xinjiang, China. Flavonoids extracted from it exhibits inhibitory activities against several influenza virus strains. Despite this fact, the antiviral properties of CST, one of such flavonoids, against the influenza virus has not been reported. Thus, the aim of this study is to investigate the anti-influenza virus efficacy and antiviral mechanism of CST.

Methods: The inhibitory activity of CST against influenza viruses was assessed by using viral titers and performing Western blot, qRT-PCR, and immunofluorescence assays in Madin-Darby canine kidney (MDCK) cells and a human monocytic cell line (THP-1). The mechanism of CST against influenza virus was analyzed by hemagglutination inhibition (HI) assay, neuraminidase (NA) inhibition assay, and Western blot.

Results: CST reduced viral titers and influenza A virus (IAV) RNA and protein synthesis in a dose-dependent manner. Mechanistically, CST had no inhibitory effect on the attachment and release processes of the viral life cycle, as indicated by the HI and NA assays. Conversely, the CST-mediated inhibition of IAV is possibly linked to the inactivation of the NF-κB/p65 signal pathway. CST also suppressed the activation of JNK MAPK and P38 MAPK in vitro. In line with NF-κB/p65 inhibition, the expression levels of proinflammatory cytokines (TNF-α, IL-1β, IL-8, and IL-10) and the inflammation-related protein COX-2 were downregulated by CST.

Conclusions: CST inhibited IAV replication by downregulating the NF-κB signal transduction pathway. CST may be a potential agent or supplement against IAV infection.

Keywords: Antiviral activity; Cirsimaritin; Influenza a virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology*
  • Artemisia / chemistry*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Dogs
  • Dose-Response Relationship, Drug
  • Flavones / isolation & purification
  • Flavones / pharmacology*
  • Gene Expression Regulation
  • Hemagglutination Inhibition Tests
  • Host-Pathogen Interactions
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / growth & development
  • Influenza A Virus, H1N1 Subtype / metabolism
  • Influenza A Virus, H3N2 Subtype / drug effects*
  • Influenza A Virus, H3N2 Subtype / genetics
  • Influenza A Virus, H3N2 Subtype / growth & development
  • Influenza A Virus, H3N2 Subtype / metabolism
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Madin Darby Canine Kidney Cells
  • Neuraminidase / antagonists & inhibitors
  • Neuraminidase / genetics
  • Neuraminidase / metabolism
  • Plant Extracts / chemistry
  • Signal Transduction
  • THP-1 Cells
  • Transcription Factor RelA / antagonists & inhibitors
  • Transcription Factor RelA / genetics*
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Viral Load / drug effects
  • Viral Proteins / antagonists & inhibitors
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • Flavones
  • IL1B protein, human
  • Interleukin-1beta
  • Interleukin-8
  • Plant Extracts
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Viral Proteins
  • Interleukin-10
  • cirsimaritin
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Neuraminidase