Clinical and Translational Research
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 26, 2023; 11(27): 6327-6343
Published online Sep 26, 2023. doi: 10.12998/wjcc.v11.i27.6327
Exploring the pharmacological mechanism of Wuzhuyu decoction on hepatocellular carcinoma using network pharmacology
Jia-Ying Ouyang, Wei-Jie Lin, Jia-Mei Dong, Yang Yang, Hai-Kui Yang, Zhi-Ling Zhou, Rui-Qi Wang
Jia-Ying Ouyang, Wei-Jie Lin, Jia-Mei Dong, Yang Yang, Hai-Kui Yang, Zhi-Ling Zhou, Rui-Qi Wang, Department of Pharmacy, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai 519000, Guangdong Province, China
Author contributions: Ouyang JY, Lin WJ, and Dong JM primarily conducted this study; Yang Y and Yang HK provided technical support in network pharmacology and molecular docking; Zhou ZL and Wang RQ provided the concept, ideas support, and manuscript revision; All authors agree to be accountable for all aspects of work ensuring integrity and accuracy.
Supported by the Xiangshan Talented Scientific Research Project of Zhuhai People’s Hospital, No. 2021XSYC-02; and Research Start Project of Zhuhai People’s Hospital, No. 2020ycqd001.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The names of the repository/repositories and search keywords(s) can be found in the article.
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: Rui-Qi Wang, PhD, Lecturer, Department of Pharmacy, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Corning Road, Zhuhai 519000, Guangdong Province, China. wangrq2020@ext.jnu.edu.cn
Received: April 21, 2023
Peer-review started: April 21, 2023
First decision: May 19, 2023
Revised: June 24, 2023
Accepted: July 28, 2023
Article in press: July 28, 2023
Published online: September 26, 2023
Processing time: 152 Days and 9.3 Hours
Abstract
BACKGROUND

Wuzhuyu decoction, a traditional Chinese medicinal formula, is effective in treating hepatocellular carcinoma (HCC).

AIM

To explore the potential mechanism of action of Wuzhuyu decoction against HCC.

METHODS

The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform. HCC was used as a search query in GeneCards, Online Mendelian Inheritance in Man, Malacards, DisGeNET, Therapeutic Target Database, and Comparative Toxicogenomics Database. The overlapping targets of the Wuzhuyu decoction and HCC were defined, and then protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. CytoHubba was used to select hub genes, and their binding activities and key active components were verified using molecular docking.

RESULTS

A total of 764 compounds, 77 active compounds, and 204 potential target genes were identified in Wuzhuyu decoction. For HCC, 9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates. A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined, including 10 hub genes (tumor necrosis factor, interleukin-6, AKT1, TP53, caspase-3, mitogen-activated protein kinase 1, epidermal growth factor receptor, MYC, mitogen-activated protein kinase 8, and JUN). There were six main active components (quercetin, kaempferol, ginsenoside Rh2, rutaecarpine, β-carotene, and β-sitosterol) that may act on hub genes to treat HCC in Wuzhuyu decoction. Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase, p53, phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt, Janus kinase-signal transducer of activators of transcription, and Hippo signaling pathways. Further verification based on molecular docking results showed that the small molecule compounds (quercetin, kaempferol, ginsenoside Rh2, rutaecarpine, β-carotene, and β-sitosterol) contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.

CONCLUSION

This study revealed that Wuzhuyu decoction may be a latent multicomponent, multitarget, and multipathway treatment for HCC. It provided novel insights for verifying the mechanism of Wuzhuyu decoction in the treatment of HCC.

Keywords: Wuzhuyu decoction; Hepatocellular carcinoma; Network pharmacology; Pharmacological mechanism; Bioinformatics

Core Tip: Six main active components (quercetin, kaempferol, ginsenoside Rh2, rutaecarpine, β-carotene, and β-sitosterol) and ten core genes (tumor necrosis factor, interleukin-6, AKT1, TP53, caspase-3, mitogen-activated protein kinase 1, epidermal growth factor receptor, MYC, mitogen-activated protein kinase 8, and JUN) were obtained from Wuzhuyu decoction. In addition, 179 pathways were obtained from Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, which indicated that Wuzhuyu decoction is a multicomponent, multitarget, and multipathway treatment for hepatocellular carcinoma. The active components of Wuzhuyu decoction may participate in these pathways via the top 10 hub genes, which achieves the therapeutic effect on hepatocellular carcinoma.