The molecular mechanism of spleen-strengthening and moisture-nourishing liver prescription in treatment of acute-on-chronic liver failure based on network pharmacology and experimental verification

Abstract

<p>Aim <br></p><p>To explore the mechanism of spleen-strengthening and moisture-nourishing liver prescription(JPLSYGF)in the treatment of acute-on-chronic liver failure using network pharmacology and the molecular docking. <br></p><p>Methods <br></p><p>Relying on TCMSP and GeneCards and other databases, the relevant targets of JPLSYGF in the treatment of acute-on-chronic liver failure were obtained. String and Cytoscape were used to construct PPI networks of targets, core targets were screened out, and DAVID was used for GO function annotation and KEGG pathway enrichment analysis. The main active ingredients of the traditional Chinese medicine compound formula for JPLSYGF were selected with a bioavailability OB value of ≥ 30% and a drug-like DL≥0.18 as the screening conditions, and the molecular docking and in vivo tests were carried out on the affinity of the main active ingredient with the core target. <br></p><p>Results <br></p><p>A total of 536 active ingredients were obtained for the treatment of acute-on-chronic liver failure, and 244 intersecting target genes and 7 core target genes were screened. Molecular docking showed that the core target genes AKT1, SRC, VEGFA, STAT3, EGFR, MAPK3, HRAS had good affinity with quercetin, the main active component in the JPLSYGF, and had strong binding activity. In addition, in vivo tests verified that the JPLSYGF could reduce the expression of HRAS, EGFR, STAT3, SRC, and VEGFA, to delay the progression of acute-on-chronic liver failure. <br></p><p>Conclusions <br></p><p>JPLSYGF may act on core targets such as HRAS, EGFR, STAT3, SRC, VEGFA and so on, to achieve the effect of treating acute-on-chronic liver failure.</p>