Protostemonine alleviates heat-killed methicillin-resistant Staphylococcus aureus-induced acute lung injury through MAPK and NF-κB signaling pathways

Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) caused by gram-positive bacteria threatens human life because effective treatments and medicines is unavailable. Protostemonine (PSN), an active alkaloid mainly isolated from the roots of Stemona sesslifolia, has anti-inflammatory effects on asthma and gram-negative bacteria-induced ALI. Here, we found that PSN exhibits anti-inflammatory effects and alleviates heat-killed methicillin-resistant Staphylococcus aureus (HKMRSA)-induced pneumonia. PSN treatment significantly attenuated HKMRSA-induced pathological injury, pulmonary neutrophil infiltration, tissue permeability and the production of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in murine ALI model. In addition, PSN decreased the content of TNF-α, IL-1β, IL-6 and the expression of iNOS, as well as the production of NO in HKMRSA-induced bone marrow derived macrophages (BMDMs). Furthermore, treatment with PSN suppressed the activation of MAPKs (e.g. p38 MAPK, JNK and ERK) and NF-κB. Collectively, our results suggest that PSN ameliorates gram-positive bacteria-induced ALI in mice by inhibition of the MAPK and NF-κB signaling pathways, and our studies suggest that PSN might be a novel candidate for treating ALI/ARDS.