Exploring the Mechanisms of Action of Quercetin for the Treatment of Cervical High-Risk-Human Papilloma Virus Using Network Pharmacology and Molecular Docking

Abstract

Objective Our objective was to investigate the therapeutic mechanism of quercetin in the management of cervical HR-HPV through the integration of network pharmacology and molecular docking techniques.

Methods The GeneCard database was utilized to analyze and identify potential therapeutic targets in HR-HPV. Subsequently, a protein–protein interaction (PPI) network was constructed by employing the String database. The visualization and construction of PPI networks were accomplished using Cytoscape. The R language was utilized to conduct Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.

Results A total of 154 active constituents of quercetin were identified through screening. Additionally, 139 target genes associated with the effects of quercetin on cervical HR-HPV were predicted. PPI analyses revealed that threonine kinase Akt1, mitogen-activated protein kinase1, human IL-6 protein, signal transducer and activator of transcription 3, and epidermal growth factor receptor (EGFR) may serve as potential targets for quercetin in the treatment of cervical HR-HPV. Furthermore, GO and KEGG analyses demonstrated that quercetin is involved in various functional pathways, biological processes, molecular categories, including the Th17 signaling pathway, tumor necrotizing factor (TNF) signaling pathway, EGFR signaling pathway, PI3K-Akt signaling pathway, among others.

Conclusion Quercetin exhibits multifaceted characteristics, targeting multiple components, pathways, and targets, in the therapeutic intervention of HR-HPV, primarily by modulating inflammatory responses, oxidation reactions, and apoptotic processes.

Keywords

HR-HPV - quercetin - network pharmacology - molecular docking

CRediT Authorship Contribution Statement

Shanyun Wang: Visualization, funding acquisition, data curation, project administration, and writing-original draft. Jing Xiao: Resources. Jianfeng Zeng: Supervision, writing-review and editing. Huisi Hong: Formal analysis. Yiming Yuan: Mehtodology. Yinhao Yin: Validation and writing-review & editing.

Publication History

Received: 02 November 2023

Accepted: 22 December 2023

Article published online:
30 March 2024

• References

• 1 Bosch FX, Broker TR, Forman D. et al. authors of ICO Monograph Comprehensive Control of HPV Infections and Related Diseases Vaccine Volume 30, Supplement 5, 2012. Comprehensive control of human papillomavirus infections and related diseases. Vaccine 2013; 31 (Suppl. 07) H1-H31
• 2 Zhang YL, Shi XP, Wei JB. et al. The distribution of human papillomavirus infection and genotypes in males. Chin J Androl 2018; 24 (07) 666-668
• 3 Xu SY. Analysis of the characteristics of male human papillomavirus infection in Hangzhou area. Med Inform (Lond) 2020; 33 (05) 137-139
• 4 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68 (06) 394-424
• 5 Sung H, Ferlay J, Siegel RL. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71 (03) 209-249
• 6 Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65 (02) 87-108
• 7 Xu X, Wang Z. Research progress on risk factors of human papillomavirus infection in cervix. Chin J. Clin Physiol 2019; 13 (04) 308-311
• 8 Wu W, Li R, Li X. et al. Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry. Viruses 2015; 8 (01) 6
• 9 Cheng Z, Sun G, Guo W. et al. Inhibition of hepatitis B virus replication by quercetin in human hepatoma cell lines. Virol Sin 2015; 30 (04) 261-268
• 10 Ren BC, Zhang YF, Liu SS. et al. Curcumin alleviates oxidative stress and inhibits apoptosis in diabetic cardiomyopathy via Sirt1-Foxo1 and PI3K-Akt signalling pathways. J Cell Mol Med 2020; 24 (21) 12355-12367
• 11 Welcker M, Orian A, Jin J. et al. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc Natl Acad Sci U S A 2004; 101 (24) 9085-9090
• 12 Mclaurin JD, Weiner OD. Multiple sources of signal amplification within the B-cell Ras/MAPK pathway. Mol Biol Cell 2019; 30 (13) 1610-1620
• 13 Zhu RR, Dai L, Dai W. The value of a combination of high-risk human papillomavirus and colposcopic cervical biopsy in the diagnosis of CIN and early invasive carcinoma. Hainan Medicine 2017; 28 (03) 423-425
• 14 Yang GL. IL-6, IL-17, IFN in vaginal lavage fluid-γ、TGF- β The clinical significance of detection in high-risk cervical HPV infection patients. Chin J Mod Med 2020; 22 (07) 23-26
• 15 Hou Y, Li Y, Li X. et al. The relationship between HPV infection and immune imbalance and abnormal cell proliferation in patients with cervical lesions. Hebei Med 2023 ;29(08)
• 16 Zhang D. Study on the relationship between the pathogenicity of HR-HPV infection and the local vaginas, Il-17, Il-23. Electron J Pract Gynecol Endocrinol 2020; 7 (32) 2-3
• 17 Shen XX, Dou BB, Hua T. et al. The expression of TNF-α, Il-12 and Il-10 in high-risk HPV 16 infected vaginal lavage fluid was correlated with the grade of cervical intraepithelial neoplasia. Chin J Hosp Infect 2021; 31 (09) 1419-1422
• 18 Fan JY, Liu YL, Tai GX. et al. The relationship between the levels of Th17/Treg cells and inflammatory factors in peripheral blood and the degree of cervical lesion and HPV risk classification. Shandong Medicine 2017; 57 (29) 41-43
• 19 Yano S, Kondo K, Yamaguchi M. et al. Distribution and function of EGFR in human tissue and the effect of EGFR tyrosine kinase inhibition. Anticancer Res 2003; 23 (5A): 3639-3650
• 20 Wang J, Kuropatwinski K, Hauser J. et al. Colon carcinoma cells harboring PIK3CA mutations display resistance to growth factor deprivation induced apoptosis. Mol Cancer Ther 2007; 6 (03) 1143-1150