Multitarget and Multipathway Regulation of Zhenqi Fuzheng Granule against Non-Small Cell Lung Cancer Based On Network Pharmacology and Molecular Docking.

Abstract

Background and Objective. The morbidity and mortality rates of non-small cell lung cancer (NSCLC) remain high. Zhenqi Fuzheng (ZQFZ) granule, which consists of Astragali Radix and Ligustri Lucidi Fructus, is commonly used to improve the immunity of cancer patients. However, the mechanism of ZQFZ granule against NSCLC is still unclear. In this study, the network pharmacology and molecular docking approaches were used to investigate the potential mechanism of ZQFZ granule on NSCLC. Methods. The ingredients in the ZQFZ granule were considered in one study based on UPLC, and the potential targets were predicted in the SwissTargetPrediction database. NSCLC targets were gathered from GeneCards, OMIM, and TTD databases. The ingredient-target-NSCLC network was drawn by Cytoscape. The protein-protein interaction was obtained from the STRING database, and the gene function and biological pathways were analyzed by Metascape. AutoDock Vina was used to verify the molecular docking between the key compounds and core targets, and PyMol visualized the results. Results. 244 targets were related to 13 candidate compounds and 1904 targets were related to NSCLC, of which a total of 106 anti-NSCLC targets were predicted. The compound-target-NSCLC network indicated that sinapinic acid, ferulic acid, asiatic acid, pratensein, and glycitein might be the key components for treating NSCLC. The 41 vital targets (out of 106 targets) above the median calculated by PPI degree were selected for bioinformatics analysis. The top 10 targets out of 41 ranked by MCC were IL-6, SRC, CTNNB1, STAT3, CASP3, TNF, EGFR, MAPK8, HSP90AA1, and PTGS2. ZQFZ granule treatment for NSCLC involved many pathways through KEGG analyses, which included pathways in cancer (hsa05200), proteoglycans in cancer (hsa05205), endocrine resistance (hsa01522), microRNAs in cancer (hsa05206), PI3K-Akt signaling pathway (hsa04151), and IL-17 signaling pathway (hsa04657). Molecular docking studies revealed that sinapinic acid, ferulic acid, asiatic acid, pratensein, and glycitein had good infinity with most core targets. Conclusions. This study indicated that ZQFZ granule with multicompounds could treat NSCLC through multitargets and multipathways.