Clinical and Translational Research
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 26, 2022; 10(33): 12104-12115
Published online Nov 26, 2022. doi: 10.12998/wjcc.v10.i33.12104
Molecular mechanisms of Baihedihuang decoction as a treatment for breast cancer related anxiety: A network pharmacology and molecular docking study
Zhong-Hui Li, Guo-Hua Yang, Fang Wang
Zhong-Hui Li, Guo-Hua Yang, Fang Wang, Department of Oncology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China
Author contributions: Li ZH wrote the manuscript; Yang GH and Wang F provided key comments and revised the manuscript; all authors approved the final manuscript.
Conflict-of-interest statement: All authors declare that there is no conflict of interest regarding the publication of this paper.
Data sharing statement: Technical appendix, statistical code, and dataset available from the manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fang Wang, MD, Chief Doctor, Department of Oncology, Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6 Huajiadi Street, Chaoyang District, Beijing 100102, China. wf074500@163.com
Received: July 15, 2022
Peer-review started: July 15, 2022
First decision: August 21, 2022
Revised: September 4, 2022
Accepted: October 12, 2022
Article in press: October 12, 2022
Published online: November 26, 2022
Abstract
BACKGROUND

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.

AIM

To explore the molecular mechanisms of BD for breast cancer related anxiety treatment.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Network pharmacology, Molecular docking, Baihedihuang decoction, Breast cancer related anxiety, Mechanism of action

Core Tip: Baihedihuang decoction (BD) has significant effects on breast cancer related anxiety; however, its molecular targets in this condition remain unknown. We conducted a network pharmacology and molecular docking study to determine whether BD ingredients target molecules and signaling pathways related to breast cancer related anxiety pathogenesis. The main active ingredients identified include verbascoside, β-sitosterol, stigmasterol, and catalpol. Target genes included CDK2, TP53, HTR2A, and ESR1, which are involved in cell cycle, apoptosis, cell autophagy, blood circulation, and other biological processes. Our results confirm that BD can treat breast cancer related anxiety through multi-component, multi-target, and multi-channel synergy.