Identification of potential targets for the treatment of liver cancer with salidroside based on network pharmacology

Background: Liver cancer is a major cause of cancer-related mortality worldwide, and effective therapeutic strategies remain limited. Salidroside, a bioactive compound derived from Rhodiola rosea, has demonstrated anti-inflammatory and anticancer properties; however, its molecular mechanisms in liver cancer remain unclear. Methods: Keywords for “liver,” “liver cancer,” and “salidroside” were identified using the PubMed MeSH database. Protein-coding target genes were retrieved from the GeneCards, Traditional Chinese Medicine Systems Pharmacology (TCMSP), UniProt, HERB, and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases. Intersection genes were identified using Venn analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed in Metascape (Homo sapiens, p < 0.05). Protein-protein interaction (PPI) networks were constructed via STRING and analyzed with Cytoscape using the Maximal Clique Centrality algorithm to identify hub genes. Finally, an integrative “liver-liver cancer-salidroside-target-signaling pathway” network was generated to visualize potential mechanisms. Results: Venn analysis identified 73 intersection genes among liver, liver cancer, and salidroside targets. GO enrichment revealed roles in cellular stress response, apoptosis regulation, and mitochondrial function, while KEGG analysis highlighted pathways including PI3K-Akt signaling, apoptosis, and cancer-related pathways. PPI analysis identified key hub genes, including KT Serine/Threonine Kinase 1 (AKT1), Hypoxia-Inducible Factor 1-Alpha (HIF1A), and B-cell lymphoma 2 (BCL2), etc. The integrated network elucidated potential interactions between salidroside, target genes, and enriched pathways. Conclusions: Salidroside may exert anti-liver cancer effects by modulating apoptosis, oxidative stress, and cancer signaling pathways via hub genes like AKT1 and HIF1A. This study provides novel insights into salidroside’s therapeutic potential, warranting further experimental validation.