This study aimed to explore the mechanisms of Feiyanning formula (FYN) on acute lung injury (ALI) using pharmacokinetics combined with network pharmacology strategy. Firstly, pharmacokinetic studies of 13 major bioactive components in normal and ALI mice were conducted using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS). Secondly, metabolomics was utilized to explore the metabolites affected by FYN. Finally, the network pharmacology was used to analyze the pharmacological mechanism of FYN's pharmacokinetic target components in ALI treatment, with western blotting (WB) experiment performed for verification. The pharmacokinetic results showed that compared to normal mice, the Cmax and AUC0-t of wogonin, oroxylin A, liquiritigenin, tetrandrine, and fangchinoline were significantly increased in ALI mice. The results of the lung tissue distribution showed that compared to normal mice, the AUC0-t of wogonin and oroxyloside was significantly increased in ALI mice; the Cmax of wogonoside and norwogonin was significantly increased in ALI mice. Metabolomics analysis showed that FYN may alleviate LPS-induced lung inflammation in mice by regulating related pathways including purine metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis in both serum and lung tissue. Network pharmacology identified 110 overlapping genes between the 13 absorbed components and ALI-related targets. In KEGG enrichment analysis, the PI3K/AKT signaling pathway was identified as a significant pathway. WB experiment confirmed that FYN reduced the expression ratios of p-PI3K/PI3K, p-AKT1/AKT1, p-EGFR/EGFR, and TLR4 levels in lung tissue of ALI mice. This study might offer a solid foundation for evaluating the clinical efficacy of FYN.
Keywords: Acute lung injury; Feiyanning formula (FYN); Metabolomics; Network pharmacology; Pharmacokinetics.
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