Schisandrin A enhances pathogens resistance by targeting a conserved p38 MAPK pathway

Area of Science:

• Immunology
• Molecular Biology
• Pharmacology

Background:

• Schisandrin A (SA), a lignan from Fructus schisandrae chinensis, has demonstrated various health benefits.
• The impact of SA on innate immunity and its underlying molecular mechanisms are not well understood.

Purpose of the Study:

• To investigate the effect of SA on innate immune response and its molecular pathways.
• To explore the therapeutic potential of SA in combating infectious diseases.

Main Methods:

• Screening of conserved immune pathways in Caenorhabditis elegans.
• Assessing resistance to Gram-negative (Pseudomonas aeruginosa, Salmonella enterica) and Gram-positive (Listeria monocytogenes) pathogens.
• Measuring antibacterial peptide gene expression and PMK-1/p38 MAPK pathway activation in C. elegans and mice.

Main Results:

• SA enhanced resistance to bacterial infections by increasing host tolerance, not by reducing bacterial load.
• SA activated the PMK-1/p38 MAPK pathway, leading to increased expression of antibacterial peptide genes.
• SA treatment improved resistance to Pseudomonas aeruginosa PA14 infection in mice and increased active PMK-1 levels.

Conclusions:

• Schisandrin A promotes innate immunity through the conserved PMK-1/p38 MAPK pathway, from invertebrates to mammals.
• This study elucidates a novel mechanism for SA's immune-boosting properties, highlighting its potential for treating infectious diseases.