Brevilin A enhances innate immunity and the resistance of oxidative stress in Caenorhabditis elegans via p38 MAPK pathway

作者:Zhu, Xinting; Liu, Fang; Wu, Qinyi; Li, Sanhua; Ruan, Guoyong; Yang, Jianbo; Yu, Changyan; Jiang, Nian; Xiao, Yi*; Liu, Yun*
来源:International Immunopharmacology, 2022, 113: 109385.
DOI:10.1016/j.intimp.2022.109385

摘要

The conserved p38/PMK-1 pathway that is an evolutionarily conserved module used by mammals and nema-todes in immune response against bacterial infections. Brevilin A (BA), a sesquiterpene lactone compound of Centipeda minima has been shown to exhibit activities such as anti-tumor, anti-bacterial and anti-protozoal. However, whether the Brevilin A influences the immune response and the underlying molecular mechanisms remain obscure. We find that 10 mu M Brevilin A increases resistance to not only the Gram-negative pathogens Pseudomonas aeruginosa and Salmonella enterica but also the Gram-positive pathogens Enterococcusfaecalis and Staphylococcus aureus. Meanwhile, Brevilin A enhances the resistance to pathogens by reducing the bacterial burden in the intestine. Through the genetic screening in C. elegans, we find that Brevilin A promotes innate immunity via p38 MAPK pathway. Furthermore, Brevilin A activates the p38/PMK-1 in the intestine for innate immune response. In addition, we also find that Brevilin A increases the resistance of oxidative stress and extends lifespan through p38 MAPK pathway. Our work suggests that Brevilin A may be a viable candidate for the treatment of infectious diseases.

  • 单位
    y; 云南大学