AUTHOR=Zhang Le , Wang Yuxing , Cao Chang , Zhu Yike , Huang Wei , Yang Yi , Qiu Haibo , Liu Songqiao , Wang Dayong 

TITLE=Beneficial effect of Xuebijing against Pseudomonas aeruginosa infection in Caenorhabditis elegans

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.949608

DOI=10.3389/fphar.2022.949608

ISSN=1663-9812

ABSTRACT=<p>In the clinical intensive care units (ICU), the traditional Chinese medicine (TCM) formulation of Xuebijing has been frequently used for treating sepsis. Nevertheless, the underlying pharmacological mechanisms of Xuebijing remain largely unclear. <italic>Caenorhabditis elegans</italic> is an important experimental host for bacterial infections. Using <italic>C. elegans</italic> as an animal model, we here examined the potential of Xuebijing treatment against bacterial infection and the underlying mechanisms. Xuebijing treatment could inhibit the reduction tendency of lifespan caused by <italic>Pseudomonas aeruginosa</italic> infection. For the cellular mechanisms of this antibacterial infection property, we found that Xuebijing treatment rescued <italic>C. elegans</italic> lifespan to be against <italic>P. aeruginosa</italic> infection by inhibiting <italic>Pseudomonas</italic> colonization in the intestinal lumen. Meanwhile, the increase in the expression of antimicrobial genes induced by <italic>Pseudomonas</italic> infection was also suppressed by Xuebijing treatment. Moreover, the beneficial effect of Xuebijing against <italic>Pseudomonas</italic> infection depended on insulin, p38 MAPK, Wnt, DBL-1/TGF-β, ELT-2, and programmed cell death (PCD)-related signals. Although Xuebijing did not show obvious antibacterial activity, Xuebijing (100%) treatment could inhibit the <italic>Pseudomonas</italic> biofilm formation and decrease the expression of virulence genes (<italic>lasA</italic>, <italic>lasB</italic>, <italic>rhlA</italic>, <italic>rhlC</italic>, <italic>phzA</italic>, <italic>phzM</italic>, <italic>phzH</italic>, and <italic>phzS</italic>) and quorum sensing (QS)-related genes (<italic>lasI</italic>, <italic>lasR</italic>, <italic>rhlI</italic>, <italic>rhlR, pqsA</italic>, and <italic>pqsR</italic>). Our results support the potential role of Xuebijing treatment against bacterial infection in hosts.</p>