Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Bushen Hugu Decoction in the Treatment of Malignant Tumor Bone Metastases

Abstract

Purpose. To explore the active compounds of the Chinese medicine prescriptions of Bushen Hugu Decoction (BHD) and demonstrate its mechanisms against malignant tumor bone metastasis (BM) through network pharmacology and molecular docking analysis.Methods. The main components and targets of BHD were retrieved from the TCMSP database, and the targets were normalized by UniProt. The Herbs-Components-Targets network of BHD was established by Cytoscape. The main BM targets were obtained from GeneCards, TTD, DrugBank, and OMIM. STRING and Cytoscape were used to construct a PPI network and obtain hub genes. DAVID and Metascape were used for GO and KEGG enrichment analyses. According to the network topology parameters, the top 4 components were selected for molecular docking verification with the core targets. Results. Compound–target network of BHD mainly contained 51 compounds and 259 corresponding targets including 107 BHD-BM targets. PPI interaction network and subnetworks identified ten hub genes. GO enrichment analysis found 1970 terms ( $p<0.05$ ), and 164 signaling pathways ( $p<0.05$ ) were found in KEGG, including PI3K-Akt signaling pathway, proteoglycans in cancer, prostate cancer, MAPK signaling pathway, and IL-17 signaling pathway. Molecular docking analysis showed that the active components of BHD, quercetin, luteolin, kaempferol, and aureusidin have good binding activity to the core targets. Conclusion. The potential molecular target and signaling pathways were found for BHD major active components. It provides guidance for the future mechanism research of the BHD in malignant tumor bone metastasis. This study also established the foundation for the new strategy for the pharmacology study of Chinese medicine.