Objective: This study aimed to determine the active ingredients of Huang Qi Si Jun Zi Tang and the targets in treating cancer-related fatigue so as to investigate the treatment mechanism of Huang Qi Si Jun Zi Tang for cancer-related fatigue.
Methods: This study adopted the method of network pharmacology. The active ingredients and targets of Huang Qi Si Jun Zi Tang were retrieved, and the targets of Huang Qi Si Jun Zi Tang in treating cancer-related fatigue were obtained using a Venn diagram. Next, a protein-protein interaction (PPI) network was constructed using the String database. The core targets of Huang Qi Si Jun Zi Tang in treating cancer-related fatigue were identified through topological analysis, and functional annotation analysis and pathway enrichment analysis were carried out. Subsequently, a compound-disease-target regulatory network was constructed using Cystoscape 3.8.0 software.
Results: A total of 250 targets of Huang Qi Si Jun Zi Tang ingredients, 1447 CRF-related genes, and 144 common targets were obtained. Through topological analysis, 61 core targets were screened. Bioinformatics annotation of these genes identified 2366 gene ontology (GO) terms and 172 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.
Conclusion: The active ingredients in Huang Qi Si Jun Zi Tang, that is, quercetin, luteolin, kaempferol, and naringenin, may act on AKT1, IL-6, VEGFA, MAPK3, CASP3, JUN, and EGFR to regulate the PI3K-Akt, TNF, and IL-17 signaling pathways, thereby suppressing inflammatory response, tumor gene expression, and tumor angiogenesis to treat CRF.
This study investigated the pharmacological basis and mechanism of Huang Qi Si Jun Zi Tang in the treatment of cancer-related fatigue using systematic pharmacology, which provides an important reference for further elucidation of the anti-cancer-related fatigue mechanism and clinical applications of Huang Qi Si Jun Zi Tang, and also provides a method protocol for similar studies in the future.