Network Pharmacology-based Investigation of the Mechanism of the Chaihu-Baizhu Herb Pair in Treating Liver Cancer

Abstract

Objective: To explore the potential active ingredients, targets, and signaling pathways of the Bupleuri Radix-Atractylodis Macrocephalae Rhizoma (Chaihu-Baizhu) herb pair in the treatment of liver cancer using network pharmacology, and to provide a theoretical basis for its molecular mechanism. Methods: Active ingredients of the Chaihu-Baizhu herb pair were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) with screening criteria of drug-likeness (DL) ≥ 0. 18 and oral bioavailability (OB) ≥ 30%, and corresponding targets were obtained. Liver cancer-related targets were acquired from the GeneCards and OMIM databases. Intersection targets were identified and visualized by a Venn diagram. A “compound-target” network was constructed using Cytoscape 3. 10. 1 software. A protein-protein interaction (PPI) network was built via the STRING platform and Cytoscape to screen core targets. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using R 4. 4. 1 software. Results: A total of 23 potential active ingredients of the Chaihu-Baizhu herb pair were screened, corresponding to 190 targets. The intersection between liver cancer-related targets and drug targets yielded 108 common targets. Core PPI network targets included TP53, BCL2, JUN, CCND1, ESR1, and MAPK1. GO enrichment analysis showed that the key targets were primarily enriched in biological processes such as “response to oxygen levels”, “response to hypoxia”, and “response to oxidative stress”. KEGG pathway enrichment analysis identified over 120 pathways, with significantly enriched pathways including the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and MAPK signaling pathway. Conclusion: The Chaihu-Baizhu herb pair may exert anti-liver cancer effects through active ingredients such as quercetin, kaempferol, and isorhamnetin, acting on core targets including TP53, BCL2, and MAPK1, and regulating multiple signaling pathways such as HIF-1α/VEGF. This study provides a preliminary network pharmacology basis for the modern scientific interpretation of the “Treating liver by strengthening the spleen” theory.