Exploring mechanism of Zilongjin in treating lung adenocarcinoma based on network pharmacology combined with experimental verification

Objective: Zilongjin (ZLJ) is a common Traditional Chinese medicine for lung adenocarcinoma (LUAD) treatment. However, its mechanisms of action remain to be elucidated. Network pharmacology was used to explore underlying mechanisms of ZLJ on LUAD. Methods: The disease-related targets were found out from the GeneCards and DisGeNET databases. Active compounds and targets of ZLJ were obtained from the HIT, TCMSP, and TCMID databases. Then, the protein-protein interaction (PPI) network was built by STRING database to identify core-hub targets of ZLJ in LUAD. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to analyze the enriched regulatory pathways of targets. Molecular docking analysis were used to evaluate interactions between potential targets and active compounds. Finally, qRT-PCR method was further to verify the results of network pharmacology. Results: A total of 124 LUAD-related targets of ZLJ and 5 active compounds of ZLJ from the relevant databases were screened out. Among these target proteins, JUN, CDH1, PPARG, and FOS were core-hub genes in PPI network. GO and KEGG pathway enrichment analysis indicated that these targets might regulate the PPAR signaling pathway in LUAD. JUN, PPARG, and FOS levels were upregulated, while CDH1 level was downregulated in LUAD cells. Conclusion: This study discerned that ZLJ may target genes such as JUN, FOS, PPARG, and CDH1 via the PPAR signaling pathway in LUAD, offering foundational insights for further exploration of ZLJ in clinical applications.