Exploring the Mechanism of Inula japonica Thunb. against Non-small Cell Lung Cancer using a computer-aided drug design approach

Abstract

Abstract Context:Inula japonica Thunb. (IJT) is widespread to treat non-small cell lung cancer (NSCLC) in China with antiasthma, antitussive, and expectorant effect. However, due to the complexity of compounds and targets, the pharmacological mechanisms of IJT needs further research. The study explores the mechanisms of IJT against NSCLC through network pharmacology, molecular docking and molecular dynamics (MD) simulation. The results showed that quercetin and luteolin were selected as major compounds, and 23 putative targets of IJT against NSCLC were picked out as major hubs. The major targets just modulated the NSCLC pathway, which included Ras, ERBB, MAPK, PI3K-Akt, calcium, and p53 signaling sub-pathways. Moreover, they involved in apoptosis, cell cycle, tumor progression, proliferation, and many other significant biological processes. The molecular docking simulation showed that all the major compounds with NSCLC pathway-relevant targets of IJT had effective binding. Further, MD simulations revealed that the lutolin-AKT1 and quercetin-AKT1 complexes possessed a steady state and bound extremely stably during molecular docking. Methods: In the present study, the ingredients and targets prediction, compound-target (C-T), and protein-protein interaction (PPI) networks analysis, molecular docking, and MD simulations were applied to mine the anti-NSCLC mechanisms of IJT.