Network Pharmacology Prediction and Molecular Docking Analysis Reveal the Mechanism of XueFu ZhuYu Decoction on Malignant Pleural Effusion

Abstract

Background: XueFu ZhuYu Decoction (XFZYD) is a classic herbal formula that shows promise in the treatment of malignant pleural effusion (MPE). However, its primary components and the underlying mechanisms of action remain unclear. Therefore, the objective of this study is to preliminarily elucidate the potential mechanisms by which XFZYD may treat MPE through network pharmacology and molecular docking.

Methods: The effective components and their corresponding targets of XFZYD were identified using the traditional chinese medicine (TCM) systems Pharmacology database, and a related network was constructed utilizing Cytoscape. Subsequently, the targets associated with MPE were retrieved from the Online Mendelian Inheritance in Man (OMIM) and GeneCards databases. We then determined the intersection between compound targets and disease targets, constructing a protein–protein interaction (PPI) network by importing these into the STRING database. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses were performed through the Metascape database. Finally, molecular docking studies between core targets and effective compound molecules were conducted.

Result: Quercetin, kaempferol, and luteolin were identified as the compounds with the highest values. The primary common targets of XFZYD in relation to MPE included STAT3, MAPK1, and MAPK3. Furthermore, GO and KEGG analyses indicated that XFZYD treatment for MPE was associated with responses to lipopolysaccharide, vesicle lumen dynamics, and protein kinase activity overall. The signaling pathways predominantly involved were the AGE-RAGE pathway, IL-17 signaling pathway, and P13K-Akt signaling pathway. Molecular docking demonstrated high affinities between the lead compounds and their target proteins.

Conclusions: The active ingredients Quercetin, kaempferol, and luteolin in XFZYD exert therapeutic effects against MPE via the PI3K-Akt signaling pathway, with key targets involving STAT3, MAPK1, and MAPK3.