Mechanism of Sangju Yin in treatment of acute lung injury based on component analysis of UHPLC-ESI-QTOF-MS/MS,network pharmacology and experimental verification
Objective To explore the mechanism of Sangju Yin in the treatment of acute lung injury(ALI).Methods The ultra-high performance liquid chromatography coupled to electrospray ionization quadrupole-time-of-flight mass spectrometry(UPLC-ESI-QTOF-MS/MS)was used to quickly identify the components of Sangju Yin absorbed in plasma.Swiss Target Prediction and GeneCards were used to screen the related targets of Sangju Yin's plasmatic components and ALI-related targets,and the potential targets of Sangju Yin's anti-ALI were confirmed by Venny.Metascape was used to analyze the pathway of gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)at the intersection target,and the protein-protein interaction network(PPI)was constructed and analyzed by String database and Cytoscape software.Based on molecular docking,the interactions between important components and targets were validated.The LPS-induced ALI rat model was conducted to clarify the regulatory effects of Sangju Yin on key targets(TNF,EGFR,STAT3,and PTGS2)in rats,using real-time fluorescent semi-quantitative polymerase chain reaction(qRT-PCR).Results A total of 38 plasmatic components of Sangju Yin were detected,and 220 drug potential targets,3 758 ALI treatment potential targets and 145 intersection targets were obtained,and 10 core components(rutin,amygdalin,liquiritin,etc.)were screened out.KEGG pathway enrichment analysis revealed that Sangju Yin may play the anti-ALI role by affecting arachidonic acid metabolism,PI3K-Akt signaling pathway and other life processes.The results of molecular docking showed that the core components such as rutin,amygdalin and liquiritin had good affinities with key targets such as TNF,EGFR and STAT3.The results of qRT-PCR further showed that Sangju Yin could significantly reverse the changes of mRNA expression of EGFR,TNF,STAT3 and PTGS2 induced by ALI(P＜0.01).Conclusion Sangju Yin may interfere with TNF,EGFR,STAT3,PTGS2 and other targets through glycyrrhizin,rutin,amygdalin and other components,then regulate arachidonic acid metabolism and PI3K-Akt signal pathways to play the crucial role in treating ALI.
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