<i>Codonopsis pilosula</i>polysaccharides attenuate<i>Escherichia coli</i>-induced acute lung injury in mice

Abstract

Acute lung injury (ALI) is an inflammatory lung disease that is caused by bacterial infection. Lipopolysaccharide (LPS), a prototype pathogen-associated molecular pattern (PAMP) from Gram-negative bacteria such as <i>Escherichia coli</i> (<i>E. coli</i>), is an essential risk factor for ALI. LPS and <i>E. coli</i> induced the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappaB (NF-κB) signaling pathways, which led to the increasing immune molecule transcription, including pro-inflammatory cytokine and chemokine secretion. <i>Codonopsis pilosula</i> polysaccharides (CPPS) exhibit various biological activities and pharmacological effects. However, the effect of CPPS on ALI caused by LPS stimulation or <i>E. coli</i> infection remains unclear. Our results showed that CPPS (6.25, 12.5, 25, or 50 μg mL^-1) could attenuate the secretion of TNF-α and IL-1β and impair the phosphorylation of ERK, p38 and p65 in <i>E. coli</i>-infected macrophages without causing toxic reactions. In addition to regulating the secretion of pro-inflammatory cytokines and the activation of MAPK and NF-κB signaling pathways, CPPS could enhance bacterial phagocytosis and intracellular killing in macrophages, and inhibit the bacterial growth of <i>E. coli</i>. <i>In vivo</i> experiments showed that CPPS attenuated LPS- and <i>E. coli</i>-induced lung damage in mice, which was characterized by decreased pro-inflammatory cytokine (TNF-α, IL-1β and IL-6) and chemokine (RANTES) production and production of the biomarkers of tissue damage (HABP2 and HMGB1) in the lungs. Altogether, this study demonstrated that CPPS have a protective effect on the lungs in LPS- and <i>E. coli</i>-induced ALI mouse models, suggesting that CPPS could be a potential drug for the treatment of ALI.