Abstract
OBJECTIVE: To investigate the effective ingredients, crucial molecular targets, and the underlying molecular mechanisms associated with Herba Epimedii (HE) that exhibits anti-cancer effects for treating thyroid cancer (TC) using the network pharmacology approach. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) public database was analysed to identify the major bioactive ingredients and target proteins associated with HE. The Human Gene (Gene Cards) database, National Center for Biotechnology Information (NCBI) gene database, and Online Mendelian Inheritance in Man (OMIM) databases were analyzed to search for the disease targets of TC. Based on the overlapped results between HE putative targets and TC targets, the "compound-disease-target" network and a protein-protein interaction (PPI) network were constructed using Cytoscape 3.8.0. The R package was used to perform the Gene Ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, the "compound-disease-pathway-target" network was drawn by integrating all the information. RESULTS: The results indicated that there were 23 effective bioactive ingredients associated with HE, covering 203 targets, 145 of which were related to TC. Through PPI network topological analysis, 53 targets (including AKT1, JUN, MAPK1, RELA, and IL6) were identified as the major targets of HE. Results recorded from GO functional analyses revealed that significant biological processes were enriched. Results from KEGG analyses revealed that the pathways, such as the TNF, IL-17, and PI3K-Akt signaling pathways, played vital roles in the HE intervention for TC. CONCLUSION: We revealed the potential mechanisms through which HE exerts anti-cancer effects in the case of TC. A holistic perspective on multiple ingredients, targets, and pathways has been presented, and the results can potentially help in developing new treatment methods for TC.