Based on network pharmacology and molecular docking technology to explore the pharmacodynamic components and mechanism of Gynostemmae Pentaphylli Herba reversing Cervical intraepithelial neoplasia.

Objective: To investigate the pharmacodynamic components of Gynostemmae Pentaphylli Herba reversing Cervical intraepithelial neoplasia (CIN) were investigated by network pharmacology, and the mechanism of action was analyzed by molecular docking technology.

Methods: The effective components and targets of Gynostemmae Pentaphylli Herba and the disease target of CIN were searched in TCMSP, Pubchem, Swiss Target Prediction, GenCards, WebGestalt, and STRING. Based on the above data and the Cytoscape software, we mapped the protein-protein interaction (PPI) co-expression network. The mechanism of Gynostemmae Pentaphylli Herba CIN treatment was identified from the enrichment analysis perspective. We performed molecular docking on the AutoDock. Finally, we carried out cell experiments for verification.

Results: Eighty-five targets matching the active ingredients of Gynostemmae Pentaphylli Herba, and 2512 CIN-related action targets were obtained. The nodal degree values of five components and the target of Gynostemmae Pentaphylli Herba in the top 5 were IL6, IL1β, TNF, TP53, and PTGS2. There were 52 intersection targets of the effective active ingredient of Gynostemmae Pentaphylli Herba and CIN. The PPI network map suggested that the main active ingredient MOL000098 (Quercetin) had the most targets (40), followed by MOL000351 (Rhamnazin) (17). Gene Ontology (GO) analysis yielded the regulation of transcription from RNA polymerase II promoter, cytoplasm, extracellular space and enzyme binding, zinc ion binding, etc. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway identified 114 signaling pathways. These pathways were mainly enriched in positive regulation of transcription from RNA polymerase II promoter, positive regulation of gene expression, cytoplasm, extracellular space, enzyme binding, zinc ion binding, Pathways in cancer, Fluid shear stress and atherosclerosis, etc. The binding energies of IL6, IL1β, TNF, TP53, and PTGS2 with Quercetin, Rhamnazin, Gypenoside XXVII_qt and Gypenoside XXVIII_qt were all less than -5 kcal·mol^-1, respectively. The messenger ribonucleic acid (mRNA) expressions of IL6, IL1β, TNF, and PTGS2 in the experimental group were higher (t = 105.700, 32.450, 18.190, and 100.400, all P < 0.001), and the mRNA expressions of TP53 was lower compared with the control group (t = 8.362, all P = 0.001).

Conclusion: Gynostemmae Pentaphylli Herba may reverse CIN through targeted action of Quercetin, Rhamnazin, and gypenosides, as well as various pathways. Our study preliminarily explored the pharmacodynamic components and mechanism of the reversal of CIN by Gynostemmae Pentaphylli Herba and verified the possible mechanism of action through cell and molecular biology experiments to understand the pharmacological mechanism of Gynostemmae Pentaphylli Herba in CIN and provide data reference for new drugs and clinical trials research, which will be of great significance for clinical treatment decisions.