Retrospective Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 6, 2023; 11(19): 4553-4566
Published online Jul 6, 2023. doi: 10.12998/wjcc.v11.i19.4553
Network pharmacology and molecular docking-based analyses to predict the potential mechanism of Huangqin decoction in treating colorectal cancer
Ying-Jie Li, Dong-Xin Tang, Hong-Ting Yan, Bing Yang, Zhu Yang, Feng-Xi Long
Ying-Jie Li, Guizhou University of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550005, Guizhou Province, China
Dong-Xin Tang, Bing Yang, Digestive Department, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, Guizhou Province, China
Hong-Ting Yan, Zhu Yang, Guizhou University of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550001, Guizhou Province, China
Feng-Xi Long, Guizhou University of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Gui Yang 550001, Guizhou Province, China
Author contributions: Li YJ and Tang DX contributed equally to this work; Yan HT designed the study; Yang B contributed to the analysis of the manuscript; Yang Z and Long FX were involved in the data acquisition and writing of this article; All authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 82260957; No. 82274610; No. 81860819; No. 81860819; and No. 81960818; Guizhou Provincial Science and Technology Program (Qian Kehe Foundation-ZK[2022] General 498, Qian Kehe Foundation-ZK [2022] General 487, Qian Kehe Support [2021] General 095, Qian Kehe Platform Talent [2020]5013); National Key R&D Program Project (2019YFC1712504); Guizhou Traditional Chinese Medicine Tumor Inheritance and Science and Technology Innovation Talent Base (No. Deaf leader-[2018] No. 3); Guizhou high-level innovative talent training plan (100 levels) (No. Qian Kehe Talents [2016] No. 4032); Yang Zhu, Guizhou Province, “Traditional Chinese Medicine Oncology” Graduate Tutor Studio (No. Teaching and research GZS-[2016]08).
Institutional review board statement: The study was reviewed and approved by the Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China, Institutional Review Board.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
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: Dong-Xin Tang, MD, Doctor, Digestive Department, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 71 Baoshan North Road, Nanming District, Guiyang 550001, Guizhou Province, China. tangdongxin@sina.com
Received: April 24, 2023
Peer-review started: April 24, 2023
First decision: May 8, 2023
Revised: May 27, 2023
Accepted: June 13, 2023
Article in press: June 13, 2023
Published online: July 6, 2023
Processing time: 67 Days and 4.8 Hours
Abstract
BACKGROUND

To analyze the potential action mechanism of Huangqin decoction (HQD) in colorectal cancer (CRC) treatment on the basis of network pharmacology and molecular docking.

AIM

To investigate the molecular mechanisms of HQD for CRC treatment by using network pharmacology and molecular docking.

METHODS

All HQD active ingredients were searched using the Systematic Pharmacology and Traditional Chinese Medicine Systems Pharmacology databases and the Bioinformatics Analysis Tool for Molecular Mechanisms in traditional Chinese medicine. Then, the targets of the active ingredients were screened. The abbreviations of protein targets were obtained from the UniProt database. A “drug–compound–target” network was constructed to screen for some main active ingredients. Some targets related to the therapeutic effect of CRC were obtained from the GeneCards, DisGeNET, Therapeutic Target Database, and Online Mendelian Inheritance in Man databases. The intersection of targets of Chinese herbs and CRC was taken. A Venn diagram was drawn to construct the intersection target interactions network by referring to the STRING database. Topological analysis of the protein interaction network was performed using Cytoscape 3.7.2 software to screen the core HQD targets for CRC. The core targets were imported into the DAVID 6.8 analysis website for gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses and visualization. Finally, molecular docking was performed using AutoDockTool and PyMOL for validation.

RESULTS

In total, 280 potential drug-active ingredients were present in HQD, including 1474 targets of the drug-active ingredients. The main active ingredients identified were betulin, tetrahydropalmatine, and quercetin. In total, 10249 CRC-related targets and 1014 drug-disease intersecting targets were identified, including 28 core targets of action such as Jun proto-oncogene, AP-1 transcription factor subunit, signal transducer and activator of transcription 3, tumor protein p53, vascular endothelial growth factor, and AKT serine/threonine kinase 1. The gene ontology enrichment functional analysis yielded 503 enrichment results, including 406 biological processes that were mainly related to the positive regulation of both gene expression and transcription and cellular response to hypoxia, etc. In total, 38 cellular components were primarily related to polymer complexes, transcription factor complexes, and platelet alpha granule lumen. Then, 59 molecular functions were closely related to the binding of enzymes, homologous proteins, and transcription factors. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis yielded 139 enrichment results, involving epidermal growth factor receptor tyrosine kinase inhibitor resistance and HIF-1 and mitogen-activated protein kinase signaling pathways.

CONCLUSION

HQD can play a role in CRC treatment through the “multi-component-target–pathway”. The active ingredients betulin, tetrahydropalmatine, and quercetin may act on targets such as Jun proto-oncogene, AP-1 transcription factor subunit, signal transducer and activator of transcription 3, tumor protein p53, vascular endothelial growth factor, and AKT serine/threonine kinase 1, which in turn regulate HIF-1 and mitogen-activated protein kinase signaling pathways in CRC treatment. The molecular docking junction clarified that all four key target proteins could bind strongly to the main HQD active ingredients. This indicates that HQD could slow down CRC progression by modulating multiple targets and signaling pathways.

Keywords: Huangqin decoction; Colorectal cancer; Network pharmacology

Core Tip: Huangqin decoction may treat colorectal cancer through multi-component targeting and modulation of multiple signaling pathways.