Exploring the mechanism of Inula japonica Thunb. against non-small cell lung cancer using a computer-aided drug design approach.

In China, Inula japonica Thunb. (IJT) is extensively used for the treatment of non-small cell lung cancer (NSCLC). However, further research is required to understand the pharmacological mechanisms of IJT owing to the complicated of the chemicals and targets. To investigate the anti-NSCLC mechanisms of IJT, network pharmacology, molecular docking, and molecular dynamics simulation were used. In network pharmacology, the TCMSP, Swiss Target Prediction, DisGeNet, and therapeutic target database databases were utilized to predict the active ingredients of IJT and their targets for the treatment of NSCLC. The DAVID database was used for gene ontology enrichment and the Kyoto encyclopedia of genes and genomes enrichment analysis of its core NSCLC-related targets. Quercetin and luteolin were selected as major compounds and 23 putative targets of IJT against NSCLC were picked out as the primary hubs. The major targets just modulated the NSCLC-pathway, which included Ras, ERBB, MAPK, PI3K-Akt, calcium, p53, and JAK-STAT signaling sub-pathways. The molecular docking results showed that all major compounds with NSCLC-pathway-relevant targets of IJT exhibited effective binding. Further, molecular dynamics simulations revealed that the luteolin-AKT1 and quercetin-AKT1 complexes possessed a steady state and bound extremely stably during molecular docking. The study demonstrates that the "multi-compounds, multi-targets and multi-pathways" mechanisms of IJT in treating NSCLC are elucidated clearly by network pharmacology, laying the foundation for the subsequent clinical application of traditional Chinese medicine.