Re-Du-Ning injection ameliorates LPS-induced lung injury through inhibiting neutrophil extracellular traps formation

Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening diseases and could occur in severe COVID-19 patients. Re-Du-Ning injection (RDN) is a tradition Chinese medicine preparation which has been clinically used for treatment of respiratory diseases including COVID-19. Purpose: To elucidate the potential mechanisms of RDN for the treatment of ALI. Methods: Female C57BL/6J mice were used to establish ALI model by intraperitoneal injection 10 mg/kg LPS, and RDN injection was intraperitoneally administered with the dose of 5 and 10 ml/kg. The cytokines were measured by ELISA and qPCR. The data related to NETs were analyzed by ELISA, immunofluorescence, Western blotting and network pharmacological approach. Results: RDN robustly alleviated LPS-induced ALI. Meanwhile, RDN downregulated the expression of pro-inflammatory cytokines, such as IL-1 beta, IL-6 and TNF-alpha. Specifically, RDN treatment inhibited the formation of neutrophil extracellular traps (NETs) and remarkably suppressed the protein of PAD4. The active compound from RDN decreased the phosphorylation of ERK1/2. Conclusion: These findings demonstrate that RDN ameliorates LPS-induced ALI through suppressing MAPK pathway to inhibit the formation of NETs.

Automated summary

The study found that Re-Du-Ning injection (RDN) can alleviate LPS-induced acute lung injury (ALI) by inhibiting the MAPK pathway to reduce the formation of neutrophil extracellular traps (NETs).