Modulation of Pseudomonas aeruginosa-induced avoidance behavior by Shen Qi pills via mitogen-activated protein kinase PMK-1 and forkhead box protein O DAF-16 in Caenorhabditis elegans

Background: Avoidance behavior is one of the core features of anxiety and related in-depth study can help to reveal the biological basis of these disorders. In recent years, traditional Chinese medicine has incorporated Shen Qi pills to treat neuropsychiatric disorders, such as depression and post-traumatic stress, and has achieved significant therapeutic effects. However, its specific mechanism of action is still unclear. Purpose: The aim of this study was to link the avoidance phenotype to psychiatric disorders by utilizing the Caenorhabditis elegans as a biological model, revealing the potential common mechanisms underlying the treatment of these disorders with Shen Qi pills. Methods: Avoidance behavior and immunity of C. elegans as a phenotypic entry point to explore the molecular mechanisms by which Shen Qi pills affects avoidance behavior with the help of pmk-1 and daf-16 mutants and RNA interference techniques. Results: We found that the intervention of Shen Qi pills can delay the avoidance behavior of C. elegans to P. aeruginosa, improve the immunity level, and reduce the up-regulation of pmk-1 and daf-16 genes induced by P. aeruginosa. Shen Qi pills did not improve the immunity of pmk-1 mutant but could still enhance the immunity of daf-16 mutant. After daf-16 knockout, Shen Qi pills could not delay its avoidance behavior, which was consistent with the results shown in the neuron-specific silencing of daf-16 C. elegans. Conclusion: These findings reveal the conclusion that Shen Qi pills regulate the avoidance behavior of C. elegans induced by P. aeruginosa via PMK-1 and DAF-16, with the latter acting directly on neurons independent of immune pathways.