The TCM prescription Ma-xing-shi-gan-tang inhibits Streptococcus pneumoniae pathogenesis by targeting pneumolysin

J Ethnopharmacol. 2021 Jul 15:275:114133. doi: 10.1016/j.jep.2021.114133. Epub 2021 Apr 20.

Abstract

Ethnopharmacological relevance: Ma-xing-shi-gan-tang (MXSGT), which is documented in the Treatise on Febrile Diseases and is a therapeutic drug, is a well-known classic prescription in China and has been widely studied. Previous studies have shown that MXSGT has various pharmacological activities, including anti-influenza virus activity, and ameliorates microvascular hyperpermeability and inflammatory reactions. However, no study has reported the effect of MXSGT in the treatment of bacterial pneumonia.

Aim of the study: In this study, the potential inhibition of MXSGT against the virulence of S. pneumoniae by targeting PLY was investigated.

Materials and methods: First, HPLC analysis was used to determine the main components of MXSGT. Then PLY protein was constructed and used for hemolysis assay and western blot to test the ability of MXSGT to inhibit PLY activity, production and widowed characteristics. The growth curve of S. pneumoniae was drawled with or without MXSGT treatment. In addition, the inhibition of MXSGT against PLY-mediated A549 cell death was examined by cytotoxicity assay. Finally, the mouse experiment was used to verify the effect of MXSGT on mouse lungs.

Results: This work has discovered that MXSGT, a TCM prescription, is an effective inhibitor of PLY, an important virulence factor that is essential for S. pneumoniae pathogenicity. MXSGT inhibits the oligomerization of PLY without affecting S. pneumoniae growth and PLY production. In addition, experimental MXSGT treatment was effective against S. pneumoniae infection both in vitro and in vivo.

Conclusion: These findings directly demonstrate the potential mechanism of the Chinese herbal formula MXSGT in the treatment of pneumococcal disease and provide additional evidence for promotion of the wide use of MXSGT in the clinic.

Keywords: Anti-infection; Ma-xing-shi-gan-tang; PLY; Streptococcus pneumoniae; Traditional Chinese medicine.

MeSH terms

  • A549 Cells
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / metabolism
  • Disease Models, Animal
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Hemolysis / drug effects
  • Humans
  • Lung / drug effects
  • Lung / pathology
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred BALB C
  • Sheep
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pneumoniae / pathogenicity
  • Streptolysins / antagonists & inhibitors*
  • Streptolysins / metabolism
  • Virulence / drug effects

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Drugs, Chinese Herbal
  • Streptolysins
  • ma-xing-shi-gan-tang
  • plY protein, Streptococcus pneumoniae