Therapeutic mechanism of hederagenin, an active component in Guizhi Fuling Pellets, against cervical cancer in nude mice.
10.12122/j.issn.1673-4254.2025.07.08
- Author:
Yinfu ZHU
1
;
Yiran LI
1
;
Yi WANG
1
;
Yinger HUANG
2
;
Kunxiang GONG
3
;
Wenbo HAO
1
;
Lingling SUN
4
Author Information
1. School of Laboratory and Biotechnology, Southern Medical University, Guangzhou 510515, China.
2. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
3. Institute of Reproductive Health and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
4. Department of Oncology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China.
- Publication Type:Journal Article
- Keywords:
Guizhi Fuling Pellets;
HPV infection;
cervical cancer;
hederagenin;
network pharmacology
- MeSH:
Female;
Animals;
Uterine Cervical Neoplasms/pathology*;
Mice, Nude;
Humans;
Mice;
Oleanolic Acid/therapeutic use*;
Drugs, Chinese Herbal/therapeutic use*;
Molecular Docking Simulation;
Xenograft Model Antitumor Assays;
Cell Line, Tumor;
STAT3 Transcription Factor/metabolism*;
Protein Interaction Maps;
Janus Kinase 2/metabolism*
- From:
Journal of Southern Medical University
2025;45(7):1423-1433
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To explore the therapeutic mechanism of Guizhi Fuling (GZFL) Pellets against cervical cancer.
METHODS:Publicly available databases were used to identify the targets of GZFL Pellets and cervical cancer to construct the protein-protein interaction (PPI) network, followed by GO biological process and KEGG pathway enrichment analysis of the hub genes. The "Traditional Chinese Medicine-Active Ingredients-Targets-Pathways" network for GZFL Pellets in cervical cancer treatment was generated using Cytoscape v10.0.0, and molecular docking of the drug and potential targets was performed to predict the specific targets of active components in Guizhi Fuling Pellets. The inhibitory effects of hederagenin, an active ingredient in GZFL Pellets, was tested in cultured cervical cancer cells and in nude mice bearing cervical cancer xenografts.
RESULTS:GZFL Pellets contain 338 active components targeting 247 action sites. A total of 10127 cervical cancer-related targets were obtained, and among them 195 were identified as potential therapeutic targets of GZFL Pellets for cervical cancer treatment, including the key targets of GABRA1, PTK2, JAK2, HTR3A, GSR, and IL-17. Molecular docking study showed low binding energies of the active components such as hederagenin, campesterol, and stigmasterol for protein-molecule interaction. GO enrichment analysis suggested that GZFL Pellets inhibited cervical cancer primarily by regulating responses to steroid hormones, oxidative stress, and lipopolysaccharides. Among the active components of GZFL Pellets, hederagenin was found to inhibit cervical cancer cells in vitro and significantly reduced STAT3 phosphorylation level in the cancer cells. In nude mice bearing cervical cancer xenografts, hederagenin effectively inhibited tumor growth rate without causing obvious adverse effects.
CONCLUSIONS:GZFL Pellets inhibit cervical cancer cell growth through its multiple active components that target different pathways. Among these components, hederagenin inhibits tumor cell growth possibly by directly binding to JAK2 protein to inhibit STAT3 phosphorylation.
