Background: As a well-known herb used in the treatment of colon adenocarcinoma (COAD), Spica Prunellae (SP) shows favorable clinical effect and safety in China for many years, but its active ingredients and therapeutic mechanisms against COAD remain poorly understood. Therefore, this study aims to uncover active ingredients and mechanisms of SP in the treatment of COAD using a combined approach of network pharmacology and bioinformatics.

Methods: A comprehensive approach mainly comprised of target prediction, network construction, pathway and functional enrichment analysis, and hub genes verification was adopted in the current study.

Results: We collected 102 compounds-related genes and 3549 differently expressed genes (DEGs) following treatment with SP, and 64 disease-drug target genes between them were recognized. In addition, a total of 25 active ingredients in SP were identified. Pathway and functional enrichment analyses suggested that the mechanisms of SP against COAD might be to induce apoptosis of colon cancer cells by regulating PI3K-Akt and TNF signaling pathways. Recognition of hub genes and core functional modules was performed by constructing protein-protein interaction (PPI) network, from which TP53, MYC, MAPK8 and CASP3 were found as the hub target genes that might play an important part in therapy for COAD. Subsequently we further compared the differential expression level and assessed the prognostic value of these four hub genes. These result of verification suggested that SP exerted therapeutic effects against COAD via a PPI network involving TP53, MYC, MAPK8 and CASP3.

Conclusion: In this study, active ingredients and mechanisms of SP in the treatment of COAD were systematically discussed, which provided the foundation for further experimental studies and might act to promote its appropriate clinical application.