4.7 Article

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

Journal

INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 113, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.intimp.2022.109385

Keywords

Brevilin A; Innate immunity; p38 MAPK pathway; C; elegans; Oxidative stress

Funding

  1. National Natural Science Foundation of China
  2. [32060033]
  3. [32160037]

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The compound Brevilin A has been found to enhance innate immunity and resistance to pathogens through the p38 MAPK pathway. It also increases resistance to oxidative stress and extends lifespan through the same pathway. These findings suggest that Brevilin A may have potential implications in the treatment of infectious diseases.
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.

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