Echinacoside attenuates Klebsiella pneumoniae-induced pneumonia via inhibition of the TLR4/NF-κB signaling

APMIS. 2025 Jan;133(1):e13507. doi: 10.1111/apm.13507.

Abstract

The Gram-negative bacterium Klebsiella pneumoniae (K. pneumoniae) is one major causative agent of community- and hospital-acquired pneumonia. Echinacoside (ECH) is a phenylethanoid glycoside isolated from Cistanche deserticola that possesses anti-inflammatory activity. Our research aimed to confirm whether ECH alleviates K. pneumoniae-induced pneumonia and explore the underlying regulatory mechanisms. BEAS-2B cells and BALB/c mice were infected by K. pneumoniae to establish the cellular and animal models, respectively, followed by ECH treatment. Inflammatory cytokine levels were detected by RT-qPCR and ELISA. The lung wet/dry (W/D) weight ratio and the myeloperoxidase (MPO) activity in lung tissues were examined. The pulmonary histopathologic changes were observed through hematoxylin and eosin (H&E) staining. The levels of TLR4/NF-κB pathway-associated molecules were estimated through western blotting, immunohistochemical, and immunohistochemical staining. K. pneumoniae infection caused lung histopathologic damage, enhanced MPO activity, elevated lung W/D weight ratio, and upregulated inflammatory cytokine levels in mice and promoted inflammatory cytokine expression in BEAS-2B cells, which were reversed by ECH treatment. K. pneumoniae infection-induced upregulation in TLR4, phosphorylated (p)-p65, and p-IκBα levels, and downregulation in IκBα levels in BEAS-2B cells and pneumonia mice were overturned by ECH treatment. ECH ameliorates K. pneumoniae-induced pneumonia through suppressing the TLR4/NF-κB pathway.

Keywords: Echinacoside; Klebsiella pneumoniae; TLR4/NF‐κB signaling pathway; inflammation; pneumonia.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Cell Line
  • Cistanche / chemistry
  • Cytokines / metabolism
  • Disease Models, Animal*
  • Glycosides* / pharmacology
  • Glycosides* / therapeutic use
  • Humans
  • Klebsiella Infections* / drug therapy
  • Klebsiella Infections* / microbiology
  • Klebsiella pneumoniae* / drug effects
  • Lung* / drug effects
  • Lung* / metabolism
  • Lung* / microbiology
  • Lung* / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C*
  • NF-kappa B* / metabolism
  • Pneumonia, Bacterial* / drug therapy
  • Pneumonia, Bacterial* / microbiology
  • Pneumonia, Bacterial* / pathology
  • Signal Transduction* / drug effects
  • Toll-Like Receptor 4* / metabolism

Substances

  • Toll-Like Receptor 4
  • NF-kappa B
  • echinacoside
  • Glycosides
  • Cytokines
  • Tlr4 protein, mouse
  • Anti-Inflammatory Agents