Enhanced Anti-Lung Cancer Effects of Steamed <i>Panacis Japonici Rhizoma</i>: Insights from Metabolomics, Network Pharmacology and Molecular Dynamics Simulation.

Abstract

<i>Panacis Japonici Rhizoma</i> (PJR), a medicinal and edible herb of the <i>Panax</i> genus, exhibits enhanced anti-lung cancer activity after steaming, a phenomenon consistent with other <i>Panax</i> species. However, the active constituents responsible for this improved efficacy and their underlying mechanisms remain unclear. In this study, we integrated UPLC-Q-TOF-MS-based metabolomics, network pharmacology, molecular docking, molecular dynamics simulations, and in vitro assays to identify the key metabolites and elucidate the mechanistic basis of steamed PJR against lung cancer. Metabolomic analysis revealed ten significantly upregulated metabolites following steaming. Network pharmacology analysis identified AKT1, EGFR, HSP90AA1, SRC, and STAT3 as core targets, primarily enriched in the MAPK, PI3K-Akt, and Ras signaling pathways. Molecular docking and molecular dynamics simulations further demonstrated stable interactions between major metabolites and core targets. In vitro experiments confirmed that steamed PJR exerted markedly stronger anti-tumor effects than its raw form. Collectively, these findings indicate that steamed PJR acts through a multi-target, multi-pathway mechanism mediated by multiple bioactive constituents, highlighting its therapeutic potential in lung cancer treatment.