Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of RSG and Phellodendron against HPV infection

Background: Human papillomavirus (HPV) is a double-stranded circular DNA virus that mainly infects the human epidermis and mucosal squamous epithelium. We aimed to explore the mechanism of the Rhizoma Smilacis Glabrae (RSG) and Phellodendron compound in the treatment of HPV by network pharmacology and molecular docking. Methods: : Potential targets and active compounds of RSG and Phellodendron, as well as HPV-related targets, were retrieved from public databases. First, the key targets were obtained by intersection of the differentially expression genes (DEGs) between HPV (+)and HPV (-)tissue samples from GSE3292 dataset and top 10 proteins from protein-protein interaction (PPI) network according to Degree. Gene set enrichment analysis (GSEA) of key targets was analyzed. Subsequently, immune microenvironmentwas explored by CIBERSORT algorithm. The competing endogenouse RNA (ceRNA) network of key targets was created. Lastly, molecular docking was performed to predict the binding activityof active ingredients with key targets. Results: : A total of 37 bioactive ingredients of RSG and Phellodendron, and 59 RSG and Phellodendron-HPV-related targets were screened. GSEA showed (ESR1, EGFR and PTEN) were associated with PI3K-AKT signaling pathway. Immune infiltration analysis showed that CD8 T cells were found more abundant in the HPV (+) groups. Moreover, lncRNA-miRNA-mRNA network containing 20 nodes (3 key targets, 13 miRNAs and 4 lncRNAs) and 29 edges was constructed. Finally, molecular docking suggested that quercetin combined well with EGFR and PTEN, and palmatine had the strong affinity with ESR1. Conclusion: 3 key targets ( ESR1 , EGFR and PTEN ) and 2 bioactive ingredients (quercetin and palmatine) were successfully identified for RSG and Phellodendron against HPV, which provided theoretical basis for the clinical application of traditional Chinese medicine compound and the molecular mechanism of human papillomavirus infection.