Network pharmacology-based identification of key pharmacological pathways of epimedium acting on hepatocellular carcinoma

Abstract

Epimedium (Epimedium Tourn. ex L.), a traditional Chinese herb, is known for its kidney-nourishing and Yang-reinforcing properties. Its flavonoids exhibit potential anticancer properties. Nevertheless, the precise mechanisms through which epimedium impacts hepatocellular carcinoma (HCC) remain unclear. To elucidate these mechanisms, we employed a network pharmacology strategy. Active ingredients of epimedium were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, whereas HCC-associated genes were extracted from five different databases. Protein-protein interaction networks were constructed using the STRING database, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses using the Database for Annotation, Visualization, and Integrated Discovery platform. Network analyses were conducted using Cytoscape 3.8.0 and R 4.0.4 with the Bioconductor package. Our findings revealed 23 active ingredients and 65 common targets in HCC, potentially modulating core targets, such as Cellular tumor antigen p53, Vascular endothelial growth factor A, RAC-alpha serine/threonine-protein kinase, Insulin-like growth factor 1 receptor, and Hepatocyte growth factor receptor. Chryseriol, luteolin, and kaempferol emerged as the top three core components affecting cancer pathways. Molecular docking studies confirmed that these ingredients effectively bind to the aforementioned targets. In summary, the therapeutic benefits of epimedium in HCC are likely attributed to bioactive ingredients such as chryseriol, luteolin, and kaempferol, which facilitate apoptosis in HCC cells. These ingredients also modulate crucial cancer-related pathways, including pidermal growth factor receptor tyrosine kinase inhibitor resistance, PI3K-Akt signaling, and vascular endothelial growth factor signaling. This study offers valuable insights into the pharmacological mechanisms underlying epimedium’s effects in HCC, highlighting its potential as a promising therapeutic agent.