Abstract
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common severe lung disease with high morbidity and mortality. Yi-Qi-Xuan-Fei-Hua-Tan decoction (YQXFHT) is based on the classical formula of Ma-Xing-Shi-Gan decoction with flavor addition. METHODS: First, a global view of the potential compound-target-pathway network based on network pharmacology was constructed to provide a preliminary understanding of active compounds. Subsequently, the in vivo efficacy of YQXFHT was verified in a mouse model. Meanwhile, the metabolic mechanism of YQXFHT in the treatment of ARDS was explored using the corresponding metabolomic profiles. RESULTS: Five active components of YQXFHT and 10 core targets for the treatment of ARDS were obtained through network pharmacological studies. Potential activities include isorhamnetin, jaranol, medicarpin, quercetin, and mandneol, and core targets include STAT3, PIK3CA, PIK3CD, NRAS, AKT1, PTPN11, JAK1, EGFR, IL-6, and CTNNB1. Besides, 10 pathways were analyzed by Kyoto Gene and Genome Encyclopedia enrichment analysis, mainly including estrogen, IL-17, TNF, FoxO, PI3k-Akt, and HIF-1 signaling pathways, etc. It was shown that the docking model between the core target and its corresponding components was stable by molecular docking. Finally, in metabolomics, it was concluded that YQXFHT can be activated by unsaturated fatty acid synthesis, linoleic acid metabolism, lysine degradation, arginine proline metabolism, and drug metabolism-cytochrome P450 metabolic pathways to exert effects on ARDS. CONCLUSION: This study highlighted the reliability and validity of the metabolomics and network pharmacology-based approach that identified and validated complexes of natural components in YQXFHT to elucidate the therapeutic mechanisms of ARDS.