Inhibitory Effect of the Traditional Chinese Medicine Ephedra sinica granules on Streptococcus pneumoniae Pneumolysin

Biol Pharm Bull. 2020;43(6):994-999. doi: 10.1248/bpb.b20-00034.

Abstract

Streptococcus pneumoniae (S. pneumoniae) is an opportunistic pathogen that causes pneumonia, meningitis and bacteremia in humans and animals. Pneumolysin (PLY), a major pore-forming toxin that is important for S. pneumoniae pathogenicity, is a promising target for the development of anti-infective agents. Ephedra sinica granules (ESG) is one of the oldest medical preparation with multiple biological activities (such as a divergent wind and cold effect); however, the detailed mechanism remains unknown. In this study, we found that ESG treatment significantly inhibited the oligomerization of PLY and then reduced the activity of PLY without affecting S. pneumoniae growth and PLY production. In a PLY and A549 cell co-incubation system, the addition of ESG resulted in significant protection against PLY-mediated cell injury. Furthermore, S. pneumoniae-infected mice showed decreased mortality, and alleviated tissue damage and inflammatory reactions following treatment with ESG. Our results indicate that ESG is a potential candidate treatment for S. pneumoniae infection that targets PLY. This finding partially elucidates the mechanism of the Chinese herbal formula ESG in the treatment of pneumococcal disease.

Keywords: Ephedra sinica granules; Streptococcus pneumoniae; anti-infection; pneumolysin; target.

MeSH terms

  • A549 Cells
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / metabolism
  • Bronchoalveolar Lavage Fluid / immunology
  • Ephedra sinica*
  • Female
  • Humans
  • Interleukin-6 / immunology
  • Lung / drug effects
  • Lung / pathology
  • Medicine, Chinese Traditional
  • Mice, Inbred BALB C
  • Plant Preparations / pharmacology
  • Plant Preparations / therapeutic use*
  • Pneumococcal Infections / drug therapy*
  • Pneumococcal Infections / immunology
  • Pneumococcal Infections / pathology
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / growth & development
  • Streptolysins / antagonists & inhibitors*
  • Streptolysins / metabolism
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Interleukin-6
  • Plant Preparations
  • Streptolysins
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • plY protein, Streptococcus pneumoniae