Andrographolide inhibits influenza A virus-induced inflammation in a murine model through NF-κB and JAK-STAT signaling pathway

Microbes Infect. 2017 Dec;19(12):605-615. doi: 10.1016/j.micinf.2017.08.009. Epub 2017 Sep 7.


Influenza viruses, the main cause of respiratory tract diseases, cause high morbidity and mortality in humans. Excessive inflammation in the lungs is proposed to be a hallmark for the severe influenza virus infection, especially influenza A virus infection. Strategies against inflammation induced by influenza A virus infection could be a potential anti-influenza therapy. Here, lethal dose of mouse-adapted H1N1 strain PR8A/PR/8/34 was inoculated C57BL/6 mice to detect the anti-influenza activity of andrographolide, the active component of traditional Chinese medicinal herb Andrographis paniculata, with or without influenza virus entry inhibitor CL-385319. Treatment was initiated on 4 days after infection. The survival rate, body weight, lung pathology, viral loads, cytokine expression were monitored in 14 days post inoculation. The combination group had the highest survival rate. Andrographolide treatment could increase the survival rate, diminish lung pathology, decrease the virus loads and the inflammatory cytokines expression induced by infection. Mechanism studies showed the NF-κB and JAK-STAT signaling pathway were involved in the activity of andrographolide. In conclusion, combination of virus entry inhibitor with immunomodulator might be a promising therapeutic approach for influenza.

Keywords: Andrographolide; Immunomodulator; Influenza viruses; JAK-STAT signaling pathway; NF-κB; Virus entry inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Andrographis / chemistry
  • Animals
  • Benzamides / therapeutic use
  • Cell Line
  • Cytokines / metabolism
  • Disease Models, Animal
  • Diterpenes / therapeutic use*
  • Dogs
  • Drug Therapy, Combination
  • Female
  • Humans
  • Inflammation / drug therapy
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Janus Kinases / metabolism*
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism*
  • Orthomyxoviridae Infections / drug therapy*
  • Piperidines / therapeutic use
  • STAT1 Transcription Factor / metabolism*
  • STAT2 Transcription Factor / metabolism*
  • Virus Internalization / drug effects


  • 3-fluoro-N-(2-(1-piperidinyl)ethyl)-5-(trifluoromethyl)benzamide
  • Benzamides
  • Cytokines
  • Diterpenes
  • NF-kappa B
  • Piperidines
  • STAT1 Transcription Factor
  • STAT2 Transcription Factor
  • Stat1 protein, mouse
  • Stat2 protein, mouse
  • andrographolide
  • Janus Kinases