Molecular mechanisms of Baihedihuang decoction as a treatment for breast cancer related anxiety: A network pharmacology and molecular docking study.

Abstract

The therapeutic effects of a combination of Chinese medicines called Baihedihuang decoction (BD) have been clinically verified, although its molecular targets in breast cancer related anxiety remain unknown. To explore the molecular mechanisms of BD for breast cancer related anxiety treatment. We used the Traditional Chinese Medicine Systems Pharmacology database to screen the active ingredients and potential targets of BD, and constructed the "drug-ingredient-target" network map with the help of Cytoscape 3.8 software. Also, we used the Online Mendelian Inheritance in Man, DrugBank, and Gencards databases to collect the disease targets of breast cancer related anxiety, and used the STRING platform to perform protein interaction analysis and construct the protein-protein interaction network. Metascape platform was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of key targets. Molecular docking technology was used to verify the drug component/target disease network. We screened 16 active ingredients of BD for breast cancer related anxiety, with 113 target proteins. There are 931 disease targets of breast cancer related anxiety, and finally, 43 key targets and 305 Kyoto Encyclopedia of Genes and Genomes pathways were generated. The main active ingredients of BD for breast cancer related anxiety are verbascoside, β-sitosterol, stigmasterol, catalpol, etc. CDK2, TP53, HTR2A, ESR1, etc. are its key targets, and the main involved signaling pathways may include neuroactive ligand-receptor interaction pathway, 5-hydroxytryptaminergic synapse, P53 signaling pathway, cGMP-PKG signaling pathway, the cAMP signaling pathway, etc. Finally, molecular docking was performed with Vina software to validate the key active ingredients in BD with the selected key action targets. The molecular docking results showed that verbascoside, β-sitosterol, stigmasterol and CDK2 could stably bind and interact through amino acid residues SER249, ARG260, PRO228, ALA282, SER276, LYS273, ASN272, etc. The therapeutic effect of BD for breast cancer related anxiety is multi-level, multi-target, and multi-pathway. The findings of this study provide ideas and basis for further research.