Effects and mechanisms of Feiyan Chuansou Oral Liquid in acute pulmonary inflammation based on TNF/NF-κB/NLRP3 signaling pathway

OBJECTIVE To investigate the protective effects and molecular mechanisms of the hospital preparation Feiyan Chuansou Oral Liquid (FYCS) on acute pulmonary inflammation.

METHODS Potential targets and pathways were identified through network pharmacology, and molecular docking was used to validate interactions between active compounds and targets. The anti-inflammatory effects of FYCS were evaluated with a lipopolysaccharide (LPS)-induced acute pulmonary inflammation mouse model and a RAW264.7 cell inflammation model. In animal experiments, the wet-to-dry weight ratio of lung tissue and the pathological changes were measured to assess FYCS′s intervention effects on acute pulmonary inflammation. Enzyme-linked immunosorbent assay (ELISA), western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were employed to detect signaling pathway-related proteins and factors in animal and cell samples.

RESULTS Based on molecular complex detection (MCODE), gene ontology (GO) annotation and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, the tumor necrosis factor(TNF)/nuclear factor kappa B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammatory pathway was identified. Experiments demonstrated that FYCS alleviated LPS-induced pulmonary edema in mice, improved pathological damage in acute pulmonary inflammation, and reduced the secretion levels of inflammatory cytokines TNF-α and interleukin-1β (IL-1β). Western blot and RT-qPCR results showed that, compared with the control group, the expression levels of NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1, IL-1β, phosphorylated NF-κB (p-NF-κB) and TNF-α were significantly increased in the model group. However, this increase was effectively suppressed in the FYCS-treated group, exhibiting effects similar to those of dexamethasone and MCC950.

CONCLUSION FYCS exerts multi-component and multi-target effects, primarily alleviating acute pulmonary inflammation by inhibiting the TNF/NF-κB/NLRP3 pathway, providing a basis for the development of traditional Chinese medicine for pediatric acute pulmonary inflammation.