Network Pharmacology and Molecular Docking to Explore the Pharmacological Mechanism of the Zuojin Pill in Treating CAG

Abstract

Background: Zuojin Pill is a widely recognized Traditional Chinese Medicine (TCM) prescription used to treat chronic atrophic gastritis (CAG). However, its mechanisms of action are not fully understood. Objectives: This study utilized a combination of network pharmacology and molecular docking to investigate the pharmacological mechanism of Zuojin Pill in the treatment of CAG. Methods: To identify the pharmacologically active ingredients of the Zuojin Pill and predict potential targets, we used the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. We obtained CAG-related targets from the Online Mendelian Inheritance in Man (OMIM) database and Genecards database. A protein-protein interaction network was established in the STRING database to explore the interactions between Zuojin Pill potential targets and CAG-related targets. Topological parameters were then calculated to identify key targets (main targets in the protein-protein interaction (PPI) network) of the Zuojin Pill for CAG treatment. The network of active ingredients and targets of Zuojin Pill in CAG treatment was visualized using Cytoscape. Additionally, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the key targets were conducted using Database for Annotation, Visualization and Integrated Discovery (DAVID). Finally, molecular docking was performed to verify the binding of active compounds with the core targets. Results: A total of 29 active ingredients corresponding to 32 key targets were identified. GO and KEGG enrichment analysis indicated that the targets of Zuojin Pill in CAG treatment primarily involve various biological processes associated with inflammation and apoptosis, as well as related pathways such as mitogen-activated protein kinases (MAPK), tumour necrosis factor (TNF) , PI3K-AKT, and others. The molecular docking results showed that isorhamnetin, quercetin, rutaecarpine, and sitosterol exhibited strong binding affinities for TNF, MAPK1, and RAC-alpha serine/threonine-protein kinase (AKT1). Among them, the binding energy between AKT1 and sitosterol was the lowest (–7 kcal/mol), indicating that it was the most stable receptor-ligand pair. Conclusions: This study used network pharmacology and molecular docking to investigate the pharmacological mechanism of Zuojin Pill in treating various pathological factors of CAG, including inflammatory reactions and apoptosis. The process involved the use of diverse factors and a “multi-pathways and multi-targets” approach. The findings of this study provide a novel perspective and theoretical basis for the clinical treatment of CAG.