AUTHOR=Tang Huaqiao , Yang Dan , Zhu Ling , Shi Fei , Ye Gang , Guo Hongrui , Deng Huidan , Zhao Ling , Xu Zhiwen , Li Yinglun 

TITLE=Paeonol Interferes With Quorum-Sensing in Pseudomonas aeruginosa and Modulates Inflammatory Responses In Vitro and In Vivo

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.896874

DOI=10.3389/fimmu.2022.896874

ISSN=1664-3224

ABSTRACT=<p>Developing quorum-sensing (QS) based anti-infection drugs is one of the most powerful strategies to combat multidrug-resistant bacteria. Paeonol has been proven to attenuate the QS-controlled virulence factors of <italic>P. aeruginosa</italic> by down-regulating the transcription of QS signal molecules. This research aimed to assess the anti-virulence activity and mechanism of paeonol against <italic>P. aeruginosa</italic> infection <italic>in vitro</italic> and <italic>in vivo</italic>. In this study, paeonol was found to reduce the adhesion and invasion of <italic>P.aeruginosa</italic> to macrophages and resist the cytotoxicity induced by <italic>P.aeruginosa</italic>. Paeonol reduced the expression of virulence factors of <italic>P.aeruginosa</italic> by inhibiting QS, thereby reducing the LDH release and damage of <italic>P.aeruginosa</italic>-infected macrophages. Paeonol can inhibit bacterial virulence and enhance the ability of macrophages to clear <italic>P.aeruginosa</italic>. In addition, paeonol exerts anti-inflammatory activity by reducing the expression of inflammatory cytokines and increasing the production of anti-inflammatory cytokines. Paeonol treatment significantly inhibited the activation of TLR4/MyD88/NF-κB signaling pathway and decreased the inflammation response of <italic>P. aeruginosa</italic>-infected macrophages. Paeonol also significantly reduced the ability of <italic>P.aeruginosa</italic> to infect mice and reduced the inflammatory response. These data suggest that paeonol can inhibit the virulence of <italic>P.aeruginosa</italic> and decrease the inflammation response in <italic>P.aeruginosa</italic>-infected macrophages and mice, which can decrease the damage induced by <italic>P.aeruginosa</italic> infection and enhance the ability of macrophages to clear bacteria. This study supports the further development of new potential anti-infective drugs based on inhibition of QS and virulence factors.</p>