Baicalein attenuates the quorum sensing-controlled virulence factors of Pseudomonas aeruginosa and relieves the inflammatory response in P. aeruginosa-infected macrophages by downregulating the MAPK and NFκB signal-transduction pathways

Drug Des Devel Ther. 2016 Jan 7;10:183-203. doi: 10.2147/DDDT.S97221. eCollection 2016.

Abstract

Burgeoning antibiotic resistance and unfavorable outcomes of inflammatory injury after Pseudomonas aeruginosa infection have necessitated the development of novel agents that not only target quorum sensing (QS) but also combat inflammatory injury with the least risk of resistance. This study aimed to assess the anti-QS and anti-inflammatory activities of baicalein, a traditional herbal medicine that is widely used in the People's Republic of China, against P. aeruginosa infection. We found that subminimum inhibitory concentrations of baicalein efficiently interfered with the QS-signaling pathway of P. aeruginosa via downregulation of the transcription of QS-regulated genes and the translation of QS-signaling molecules. This interference resulted in the global attenuation of QS-controlled virulence factors, such as motility and biofilm formation, and the secretion into the culture supernatant of extracellular virulence factors, including pyocyanin, LasA protease, LasB elastase, and rhamnolipids. Moreover, we examined the anti-inflammatory activity of baicalein and its mode of action via a P. aeruginosa-infected macrophage model to address its therapeutic effect. Baicalein reduced the P. aeruginosa-induced secretion of the inflammatory cytokines IL-1β, IL-6, IL-8, and TNFα. In addition, baicalein suppressed P. aeruginosa-induced activation of the MAPK and NFκB signal-transduction pathways in cocultured macrophages; this may be the mechanism by which baicalein inhibits the production of proinflammatory cytokines. Therefore, our study demonstrates that baicalein represents a potential treatment for P. aeruginosa infection because it clearly exhibits both antibacterial and anti-inflammatory activities.

Keywords: Pseudomonas aeruginosa; baicalein; inflammatory cytokines; quorum sensing; signal transduction; virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Inflammatory Agents / pharmacology
  • Cytokines / metabolism
  • Down-Regulation / drug effects
  • Flavanones / pharmacology*
  • Inflammation / drug therapy
  • Inflammation / microbiology
  • MAP Kinase Signaling System / drug effects
  • Macrophages / drug effects
  • Macrophages / microbiology
  • Male
  • Microbial Sensitivity Tests
  • NF-kappa B / metabolism
  • Pseudomonas Infections / drug therapy
  • Pseudomonas aeruginosa / drug effects*
  • Quorum Sensing / drug effects*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Virulence Factors / metabolism

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Cytokines
  • Flavanones
  • NF-kappa B
  • Virulence Factors
  • baicalein