Abstract: Objective To explore the molecular mechanism mediating the inhibitory effect of Chuanxiong Rhizoma against brain metastasis of lung cancer using network pharmacology methods and molecular docking. Methods The chemical components of Chuanxiong Rhizoma and their targets were obtained through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The relevant targets for brain metastasis of lung cancer were screened using the GeneCards database. Clusterpro-filerR package was used to perform GO and KEGG enrichment analysis. Cytoscape and STRING database were used to construct the "active ingredient- target-disease" network and protein-protein interaction (PPI) network of Chuanxiong Rhizoma. The core components of Chuanxiong Rhizoma and their targets in the treatment of lung cancer brain metastasis were screened based on the topological parameters, and the results were verified using molecular docking and in Chuanxiong extract- treated human lung cancer PC9 cells by detecting the core target with Western blotting. Results Forty-eight active ingredients of Chuanxiong Rhizoma including (Z)-ligustilide, butylphthalide, oleic acid, and myricetone were screened, which target 49 proteins including INS, BDNF, FOS, VEGFA, PTGS2, ESR1, MAPK14, and PTGS1. These proteins participated in 57 biological functions such as nuclear receptor activity, ligand activation, and transcription factor activity, involving 40 signaling pathways such as prolactin signaling pathway, breast cancer, and etrogen signaling. The results of molecular docking showed that myricetone, butylphthalide, 4-hydroxy-3 butylphthalide, (Z)-ligustilide, and ligustalide-E, among others, had strong affinities to 7 cores targets including BDNF, FOS, PTGS2, and MAPK14. In PC9 cells, treatment with Chuanxiong Rhizoma extract resulted in significant reductions in the phosphorylation levels of PI3K, Akt and VEGF (P<0.01). Conclusion Chuanxiong Rhizoma contains multiple active ingredients against brain metastasis lung cancer, and these ingredients act on multiple targets involving multiple signal pathways and biological functions.

Key words: Chuanxiong Rhizoma; network pharmacology; molecular docking; brain metastasis of lung cancer