Research on the Mechanism of Si Xian Decoction in Treating Acute Leukemia Based on Network Pharmacology and Molecular Docking Technology

Abstract

Abstract Objective Our objective was to investigate the mechanism of action of the Si Xian Decoction (SXD) in treating acute leukemia (AL) using network pharmacology and molecular docking techniques. Methods The chemical components of the four medicinal herbs of Shengdi (Rehmanniae Radix), Baimaogen (Imperatae Rhizoma), Xiaoji (Cirsii Herba), and Pugongying (Taraxaci Herba) in the SXD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM), and Encyclopedia of Traditional Chinese Medicine (ETCM). A natural active chemical component dataset for the SXD was established. Human Gene Database (Gencards), Database of Gene-Disease Associations (DisGeNET), Database for Drug and Drug Target Information (DrugBank), and Human Disease Database (MalaCards) were searched to obtain AL-related targets and to establish a disease target database. After obtaining the intersection targets of drugs and diseases, a Venn diagram of the common targets was drawn online. A drug-disease protein interaction network was constructed using the String 11.5 platform, and a “drug-disease-target-signal pathway” network was built using Cytoscape 3.8.2 software to obtain relevant target network topology parameters. Results By searching the TCMSP, BATMAN-TCM, and ETCM databases, 30 active components of the SXD and 677 related targets were obtained. From Gencards, DrugBank, MalaCards, and DisGeNET databases, 12,110 potential AL disease targets were obtained. Using the ClusterProfiler package of the R4.2.2 platform, 1,011 entries of gene ontology information were enriched, including 467 biological process entries, 236 molecular function entries, and 308 cellular component entries. Additionally, 220 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were obtained, mainly involving chemical carcinogen receptor activation, lipid and atherosclerosis, fluid shear stress and atherosclerosis, prostate cancer, and the role of the advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications. Network topology analysis revealed that the main active components of SXD treating AL include γ-aminobutyric acid, adenosine, quercetin, scopolamine, and taraxasterol. Conclusion The treatment of AL with the SXD is a process of multicomponent, multitarget, and multisignal pathway coordination. Network pharmacology provides a solid research basis for elucidating the mechanism of action of SXD in the treatment of AL.