Andrographolide protects against the intestinal barrier dysfunction and inflammatory response through modulating ETEC virulence factors in a mouse model of diarrhea

Infectious diarrhea is a common disease that endanger both human and livestock animals. However, there are limited safety strategy for preventing Enterotoxigenic Escherichia coli (ETEC) induced diarrhea. A mouse diarrhea model was established by orally administering ETEC following andrographolide pretreatment. Pretreatment with andrographolide improved the body weight losses, diarrhea, intestinal barrier dysfunction and inflammation of ETEC infected mice. Andrographolide pretreatment protected against the ETEC-induced downregulation of intestinal Na⁺/H⁺ exchange protein 3 (Nhe3) and upregulation of cystic fibrosis transmembrane conductance regulator (Cftr) mRNA expression. Andrographolide pretreatment also reduced coliform colonization in the jejunum but did not affect fecal coliform levels in infected mice. By using an in vitro model, it was shown that andrographolide downregulated the expression of virulence factors involved in ETEC k88 colonization, as well as heat-labile and heat-stable enterotoxins. These results unveil a novel finding that andrographolide protect against ETEC infection by regulating its virulence factors.