Background: Cancer patients who receive anthracycline-based chemotherapy regimens often discontinue chemotherapy due to cardiotoxicity. Preventing and reducing anthracycline-induced cardiotoxicity (ACT) is a hot topic in cardio-oncology research. Network pharmacology is a new discipline that integrates pharmacology, bioinformatics, and systems biology. It can be used to analyze the mechanism of action of drugs in the body from a holistic perspective by constructing a "disease-gene-drug" network, providing a new method to explore compounding mechanisms of Chinese medicine. Based on network pharmacology, this study explored the mechanism of the reduction of cardiotoxicity of anthracyclines by Qishen Huanwu Capsule.
Methods: The active ingredients of Qishen Huanwu Capsule and their targets were screened based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Chemistry Database. The target genes of ACT were screened through the PharmGkb, GeneCards, Online Mendelian Inheritance in Man (OMIM), Genetic Association Database (GAD), and Therapeutic Target Database (TTD). The Venny2.1 online analysis tool was used to construct a Venn diagram to obtain the common targets of ACT and Qishen Huanwu Capsule. The STRING platform was used to construct the protein-protein interactions (PPI) among the common targets; ClueGO software was used to perform Gene Ontology (GO) biological process enrichment analysis for the common targets; the R language was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; and the results were visualized using Cytoscape software.
Results: The predictions indicate that Qishen Huanwu Capsule has 35 main active ingredients capable of reducing the cardiotoxicity of anthracyclines and that there are 36 common targets of ACT and Qishen Huanwu Capsule that are enriched in 133 biological processes and 27 signaling pathways.
Conclusions: Qishen Huanwu Capsule regulates phosphatidylinositol 3‑kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), forkhead box class O (FoxO) and other signaling pathways by regulating targets such as RAC-alpha serine/threonine protein kinase (Akt1), mitogen-activated protein kinase 1 (MAPK1), and mitogen-activated protein kinase 8 (MAPK8) and thereby inhibits oxidative stress and regulates apoptosis and autophagy to reduce the cardiotoxicity of anthracyclines.
Keywords: Qishen Huanwu Capsule; anthracycline-induced cardiotoxicity (ACT); mechanism; network pharmacology.