Antiviral effects of modified dingchuan decoction against respiratory syncytial virus infection in vitro and in an immunosuppressive mouse model

J Ethnopharmacol. 2013 May 2;147(1):238-44. doi: 10.1016/j.jep.2013.03.012. Epub 2013 Mar 15.

Abstract

Ethnopharmacological relevance: Modified dingchuan decoction (MDD) is used in traditional Chinese medicine for the treatment of cough, chronic bronchitis, asthma and viral pneumonia.

Aim of the study: To investigate antiviral potentials of MDD in respiratory syncytial virus (RSV) infected mice.

Materials and methods: MDD and each component were evaluated for antiviral efficacy against RSV in vitro in cell culture. Mice were were treated with cyclophosphamide and infected with RSV. Then, treatments with MDD at doses of 1.75 g/kg, 3.5 g/kg and 7.0 g/kg, respectively, were oral administrated daily for 5 days after challenge. The levels of Eotaxin, IL-4 and IFN-γ in serum and lung tissue were detected by ELISA, viral loads in lung tissues were detected by RFQ-PCR while expressions of NF-κB and TLR4 mRNA were also detected by RFQ-PCR.

Results: A selective index of >36.8 (2.5 times greater than that observed for ribavirin) was determined in the in vitro studies for this herbal medicine. MDD exhibited significant antiviral and anti-inflammatory effects on decreasing levels of Eotaxin, IL-4 and IFN-γ in serum and lung tissue, inhibiting pneumonia, decreasing lung viral loads and reversaling RSV-induced inflammation through down-regulation of TLR4 and NF-κB mRNA expression in the lung tissue of RSV-infected mice.

Conclusions: MDD could exhibit antiviral and anti-inflammatory effects on RSV-infected mice as a suppressor of Eotaxin, IL-4 and IFN-γ. These effects appeared to be mediated by inhibitions of TLR4 and NF-κB activation. Therefore, MDD could provide an effective therapeutic approach for RSV and its subsequent viral bronchitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology*
  • Bronchiolitis, Viral / blood
  • Bronchiolitis, Viral / drug therapy*
  • Bronchiolitis, Viral / genetics
  • Bronchiolitis, Viral / immunology
  • Bronchiolitis, Viral / virology
  • Cell Line, Tumor
  • Chemokine CCL11 / blood
  • Cyclophosphamide / pharmacology
  • Disease Models, Animal
  • Down-Regulation
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology*
  • Humans
  • Immunocompromised Host*
  • Immunosuppressive Agents / pharmacology
  • Interferon-gamma / blood
  • Interleukin-4 / blood
  • Lung / drug effects*
  • Lung / immunology
  • Lung / virology
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Phytotherapy
  • Plants, Medicinal
  • RNA, Messenger / metabolism
  • Respiratory Syncytial Virus Infections / blood
  • Respiratory Syncytial Virus Infections / drug therapy*
  • Respiratory Syncytial Virus Infections / genetics
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus, Human / drug effects*
  • Respiratory Syncytial Virus, Human / growth & development
  • Toll-Like Receptor 4 / drug effects
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Viral Load

Substances

  • Antiviral Agents
  • Ccl11 protein, mouse
  • Chemokine CCL11
  • Drugs, Chinese Herbal
  • Immunosuppressive Agents
  • NF-kappa B
  • RNA, Messenger
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Interleukin-4
  • Interferon-gamma
  • Cyclophosphamide