Network Pharmacology-based Mechanistic Study on Prunellae Spica for the Treatment of Endometrial Cancer

Abstract Ethnopharmacological relevance: Prunellae spica belongs to the Labiatae family and it clears the liver and purges fire, improves vision, and disperses swelling. Clinically, Prunellae spica plays diverse antibacterial, antiviral, and anti-cancer roles and is involved in immune regulation but its mechanism of action is unknown for exerting the therapeutic effects. This study comprehensively analyzes the mechanism of Prunellae Spica for Endometrial cancer (EC) based on multiple databases such as Network Pharmacology and TCGA, which will help to provide new ideas for targeted therapy for EC. Materials and methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), together with Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM), and GeneCards were employed to retrieve Prunellae spica-related active components and corresponding targets, along with the target genes related to EC. A protein-protein interaction (PPI) network was constructed after the shared target genes were screened. Subsequently, functional annotations were obtained through Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A drug component-target-disease network was established to visualize the overall pharmacological effects exerted by Prunellae spica on EC. Bioinformatics analyses for the genes of interest and common genes targeted by traditional Chinese medicine (TCM) were performed. Molecular docking inferred the possibility of treating EC using Prunellae spica. Results Eleven active components related to Prunellae spica were identified from the screen. By converting their names in the UniProt database, 185 target genes of Prunellae spica were retrieved, 83 of which could interact with EC cells. Bioinformatics analysis inferred that the pharmacological effects of Prunellae spica on EC involved the positive and negative regulation of apoptosis, positive regulation of gene expression, and cell cycle regulation, along with a strong association with DNA synthesis. Quercetin, kaempferol, and luteolin were the active components of Prunellae spica, which could bind well to TP53, AKT1, JUN, BCL2, Myc, TNF, and CASP3, according to the molecular docking study. Conclusions The mechanistic underpinning of Prunellae spica for treating EC involves multiple targets and signaling pathways. In summary, the plausible mechanisms of Prunellae spica demonstrated pharmacologically in this study provide a rationale for TCM as EC treatment. However, experiments are further needed to strengthen the evidence for using Prunellae spica, a promising candidate for treating EC.