Preliminary study of Yinhuapinggan granule against H1N1 influenza virus infection in mice through inhibition of apoptosis

Pharm Biol. 2020 Dec;58(1):979-991. doi: 10.1080/13880209.2020.1818792.

Abstract

Context: Yinhuapinggan granule (YHPG) is frequently used for treating fever, cough, and viral pneumonia in traditional Chinese medicine.

Objective: This study investigated the antiviral effects of YHPG in H1N1 influenza virus (IFV)-infected mice and its possible mechanism.

Materials and methods: ICR mice were intranasally infected with 10 LD50 viral dose of IFV and then oral administration of YHPG (6, 12, and 18 g/kg) or oseltamivir (positive control) once a day for 2 or 4 consecutive days, six mice in each group. The lung, spleen and thymus indexes of IFV-infected mice, the expression of viral loads and pathological changes in lung tissues were performed to evaluate the antiviral effects of YHPG. Real-time PCR, immunohistochemistry and western blot assays were used to determine the expression of Bax, Bcl-2 and caspase-3.

Results: LD50 in mice was 10-3.5/0.02 mL. YHPG (6, 12, and 18 g/kg) dose-dependently decreased the lung index and viral load; the inhibition ratio of lung index was 5.31, 18.22, and 34.06%, respectively. Further detection revealed that YHPG (12 and 18 g/kg) significantly attenuated lung pathological changes, and increased the spleen and thymus indexes. Moreover, YHPG significantly down-regulated the mRNA and protein expression of Bax and caspase-3 in lung tissues of mice infected with IFV, and up-regulated the expression of Bcl-2.

Conclusions: YHPG has significant antiviral effects in IFV-infected mice, partially by inhibiting influenza virus replication and regulating the occurrence of apoptosis induced by influenza virus infection, suggesting that YHPG may be a promising antiviral agent with potential clinical application prospects.

Keywords: Traditional Chinese medicine; apoptosis signalling pathway.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Apoptosis / drug effects
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / isolation & purification
  • Male
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred ICR
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / virology
  • Viral Load / drug effects
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Drugs, Chinese Herbal
  • yinhuapinggan

Grants and funding

This work was supported by National Science Foundation of China [grant number 81930111], [grant number 81603531], [grant number 81573868], [grant number 81630105]; Zhejiang Provincial Natural Science Foundation [grant number LZ17H270001]; and was sponsored by Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents.