Mechanism of polygonum capitatum intervention in pulmonary nodule based on network pharmacology and molecular docking technology.

Abstract

The present study utilizes network pharmacology and molecular docking methodologies to investigate the mechanism of action behind the intervention of Polygonum capitatum Buch.-Ham.ex D. Don (THL) in treating pulmonary nodules (PN). This research aims to provide a theoretical foundation for broadening the clinical application of THL. Active components of THL were identified and screened through an extensive literature review and the PharmMapper database, followed by an analysis of their target interactions. Relevant targets associated with PN were selected using databases such as OMIM and GeneCards, with an intersection of the two sets being determined. STRING11.5 facilitated the acquisition of protein-protein interaction data, which was then imported into Cytoscape 3.7.2 to establish a protein interaction network topology. This enabled the identification of pivotal targets affected by THL intervention in PN. The study further employed the Metascape database to conduct GO and KEGG bioinformatics enrichment analyses, which illuminated core pathways involved in THL's therapeutic effects on PN. A comprehensive component-target-pathway diagram was constructed utilizing Cytoscape 3.7.2 software, with molecular docking validations carried out via Maestro software. A total of 49 active THL ingredients were discerned, implicating 67 PN-relevant targets. Subsequent software analysis pinpointed 10 key targets, including ALB, EGFR, and SRC. Molecular docking studies indicated strong binding affinities for most protein-compound pairs, with 44 out of 60 docking results exhibiting binding energies below -5 kcal/mol. Enrichment analysis highlights that key targets are mainly involved in pathways such as cancer, lipid metabolism and atherosclerosis, estrogen signaling, IL-17 signaling, complement and coagulation cascades, and chemical carcinogenesis through receptor activation. Through comprehensive network pharmacological approaches, this research delineates the synergy of THL's multiple components, targets, and pathways in mitigating PN. It posits that primary active ingredients of THL - quercetin, salidroside, and oleanolic acid - may exert effects on targets like ALB, EGFR, SRC, potentially modulating pathways associated with cancer, lipid and atherosclerosis, and IL-17 signaling in the context of PN intervention.