The immuno-regulatory impact of orally-administered Hypericum perforatum extract on Balb/C mice inoculated with H1n1 influenza A virus

PLoS One. 2013 Sep 30;8(9):e76491. doi: 10.1371/journal.pone.0076491. eCollection 2013.


Hypericumperforatum (H. perforatum) ethanol extract has been found to inhibit lipopolysaccharide-induced production of inflammatory mediators and cytokines in cultured macrophages. Therefore, it may be able to protect the host from excessive inflammation during viral infection. In the current study, the immune-regulatory effect of H. perforatum extract was evaluated in A549 lung epithelial cells and BALB/c mice exposed to Influenza A/PR/8/34 H1N1 virus. In A549 cells, the extract (30 µg/mL) significantly inhibited influenza virus induced monocyte chemotactic protein (MCP)-1 and interferon-γ induced protein 10 kD (IP-10), but dramatically increased interleukin-6 (IL-6). In mice inoculated intranasally with 10(7.9) EID50 of Influenza A/PR/8/34 H1N1 (high dose), daily oral treatment of H. perforatum extract at a rate of 110 mg/kg of body weight increased lung viral titer, bronchoalveolar lavage (BAL) pro-inflammatory cytokine and chemokine levels, and the infiltration of pro-inflammatory cells in the lung 5 days post-inoculation, as compared to ethanol vehicle treated mice. Transcription of suppressor of cytokine signaling 3 (SOCS3) was increased by H. perforatum extract both in A549 cells and BALB/c mice, which could have interrupted anti-viral immune response and thus led to the inefficient viral clearance and increased lung inflammation. H. perforatum treatment resulted in minor reduction in viral titer without affecting body weight when mice were inoculated with a lower dose (~10(5.0) EID50) and H. perforatum was applied in the later phase of infection. Mice challenged intranasally with high dose of influenza virus (10(7.9) EID50) suffered from a higher mortality rate when dosed with H. perforatum extract. In conclusion, the current study showed that SOCS3 elevation by H. perforatum may cause impaired immune defense against influenza virus infection and lead to higher mortality.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cell Line
  • Chemokine CXCL10 / antagonists & inhibitors
  • Chemokines / analysis
  • Cytokines / analysis
  • DNA Primers / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / drug effects*
  • Humans
  • Hypericum / chemistry*
  • Influenza A Virus, H1N1 Subtype*
  • Interleukin-6 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Monocyte Chemoattractant Proteins / antagonists & inhibitors
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / immunology*
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism


  • Chemokine CXCL10
  • Chemokines
  • Cxcl10 protein, mouse
  • Cytokines
  • DNA Primers
  • Interleukin-6
  • Monocyte Chemoattractant Proteins
  • Plant Extracts
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins