Analysis of Mechanism of Action of Jianpi Tongluo Lishui Prescription in Treating Decompensated Cirrhosis of Liver-Depression and Spleen-Deficiency with Blood Stasis Type Based on Network Pharmacology
Abstract: Objective: To analyze the mechanism of action of Jianpi Tongluo Lishui Prescription in treating decompensated cirrhosis (DLC) of liver-depression and spleen-deficiency with blood stasis type using network pharmacology and molecular docking technology. Methods:The active ingredients and corresponding targets of Jianpi Tongluo Lishui Prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform( TCMSP) and the HERB database. The targets standardized by the UniProt database were combined to obtain the "medicine-ingredient-target" data of the compound, and the medicine-ingredient interaction network was constructed using Cytoscape software. The targets related to DLC were searched in the GeneCards,National Center for Biotechnology Information (NCBI), and Online Mendelian Inheritance in Man (OMIM) databases. According to the main clinical phenotypes of DLC of liver-depression and spleen-deficiency with blood stasis type,relevant targets were retrieved from the Syndrome Ontology for Traditional Chinese Medicine and Multidimensional Quantitative Association Calculation Platform (SoFDA). The intersection of disease targets and syndrome targets was taken to obtain the diseasesyndrome corresponding targets. The common gene targets of the prescription′s ingredients and the "disease-syndrome" were uploaded to the STRING database for protein-protein interaction (PPI) analysis,and key targets were screened. The Metascape online analysis system was used for Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking verification was performed on key ingredients and core targets. Results:A total of 127 active ingredients and 443 related targets were identified from the 16 core drugs of Jianpi Tongluo Lishui Prescription. A total of 921 disease targets of DLC of liverdepression and spleen-deficiency with blood stasis type were obtained, and 156 disease targets corresponding to primary and secondary symptoms were retrieved via the SoFDA platform. There were 19 overlapping targets among Jianpi Tongluo Lishui Prescription, DLC, and liver-depression and spleen-deficiency with blood stasis syndrome. The top three core ingredients of the prescription were quercetin, β-sitosterol, and luteolin. PPI network analysis identified core targets including interleukin-6 (IL-6),tumor protein p53 (TP53),glucocorticoid receptor (NR3C1),V-myc avian myelocytomatosis viral oncogene homolog (MYC),epidermal growth factor receptor (EGFR),and transforming growth factor beta 1 (TGFβ1). Enrichment analysis showed that the 16 core Chinese herbs of the prescription mainly exerted effects in regions such as receptor complexes, membrane rafts, and membrane microdomains, involving biological processes including protein kinase modulator activity, kinase modulator activity, and transcription factor binding. Molecular docking results demonstrated stable binding between the active ingredients (quercetin,β-sitosterol, and luteolin) and the core targets (NR3C1,and MYC). Conclusion:Jianpi Tongluo Lishui Prescription may act on core targets such as NR3C1 and MYC through its core ingredients (quercetin,β-sitosterol,and luteolin) to regulate signaling pathways like FoxO and biological processes such as the positive regulation of miRNA transcription,thereby exerting a therapeutic effect on DLC of liver-depression and spleen-deficiency with blood stasis type.