Paeoniflorin increases the survival of Pseudomonas aeruginosa infected Caenorhabditis elegans at the immunosuppression stage by activating PMK-1, BAR-1, and EGL-1 signals

Arch Pharm Res. 2023 Jul;46(7):616-628. doi: 10.1007/s12272-023-01459-w. Epub 2023 Aug 3.

Abstract

Paeoniflorin is the major active compound of total glycoside of paeony in Paeonia lactiflora Pall. Although several aspects of beneficial effects of paeoniflorin have been described, whether the paeoniflorin treatment is helpful for inhibiting the pathogen infection-induced immunosuppression remains largely unclear. Using the immunosuppression model in Caenorhabditis elegans induced by Pseudomonas aeruginosa infection, we here examined the beneficial effect of paeoniflorin treatment against the immunosuppression induced by bacterial pathogen infection. In this immunosuppression model, we observed that the survival rate of P. aeruginosa infected nematodes at the immunosuppression stage could be significantly increased by 25-100 mg/L paeoniflorin treatment. P. aeruginosa accumulation in intestinal lumen of nematodes at the immunosuppression stage was reduced by paeoniflorin treatment. Paeoniflorin could activate the expressions of antimicrobial genes (lys-1 and lys-8) in nematodes at the immunosuppression stage. Moreover, at the immunosuppression stage, paeoniflorin treatment increased the expressions of bar-1, pmk-1, and egl-1 required for the control of innate immunity against bacterial infection. Meanwhile, RNAi of bar-1, pmk-1, and egl-1 inhibited the beneficial effect of paeoniflorin treatment in increasing the survival, reducing the P. aeruginosa accumulation in intestinal lumen, and activating the expressions of antimicrobial genes (lys-1 and lys-8) in nematodes at the immunosuppression stage. Therefore, paeoniflorin treatment could effectively inhibit the immunosuppression induced by bacterial pathogen infection in the hosts.

Keywords: Bacterial infection; C. elegans; Immunosuppression; Paeoniflorin.

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans*
  • Immunity, Innate
  • Immunosuppression Therapy
  • Pseudomonas aeruginosa / metabolism
  • Repressor Proteins / metabolism
  • Repressor Proteins / pharmacology

Substances

  • Caenorhabditis elegans Proteins
  • peoniflorin
  • EGL-1 protein, C elegans
  • Repressor Proteins