Forsythoside B, the active component of Frosythiae fructuse water extract, alleviates Streptococcus pneumoniae virulence by targeting pneumolysin

J Appl Microbiol. 2024 Oct 3;135(10):lxae251. doi: 10.1093/jambio/lxae251.

Abstract

Aims: To explore the therapeutic potential of Forsythoside B in treating Streptococcus pneumoniae (S. pneumoniae) infections, focusing on its ability to inhibit pneumolysin activity and protect cells from damage.

Methods and results: Hemolysis tests were used to evaluate Forsythoside B's inhibitory effect on pneumolysin activity, while growth curve analysis assessed its impact on S. pneumoniae growth. Western blotting and oligomerization analysis were conducted to examine its influence on pneumolysin oligomerization. Cytotoxicity assays, including LDH release and live/dead cell staining, evaluated the protective effects of Forsythoside B against pneumolysin-induced damage in A549 cells. Additionally, a mouse model was employed to test the effects on survival rates, lung bacterial load, and inflammation. The results showed that Forsythoside B significantly inhibited pneumolysin activity, reduced its oligomerization, and protected A549 cells from damage without affecting bacterial growth. In the mouse model, it improved survival rates and reduced lung inflammation, indicating its potential as a therapeutic agent against S. pneumoniae infections.

Conclusions: Forsythoside B shows potential as a therapeutic agent for treating pneumonia, particularly in infections caused by S. pneumoniae.

Keywords: Streptococcus pneumoniae; anti-infection; forsythoside b; frosythiae fructuse; pneumolysin.

MeSH terms

  • A549 Cells
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / metabolism
  • Caffeic Acids* / pharmacology
  • Disease Models, Animal
  • Glucosides / pharmacology
  • Humans
  • Mice
  • Plant Extracts* / pharmacology
  • Pneumococcal Infections / drug therapy
  • Pneumococcal Infections / microbiology
  • Streptococcus pneumoniae* / drug effects
  • Streptolysins
  • Virulence / drug effects

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • forsythoside B
  • Glucosides
  • Plant Extracts
  • plY protein, Streptococcus pneumoniae
  • Streptolysins
  • Caffeic Acids