Network Pharmacology and Molecular docking Analysis on Mechanisms and Molecular Targets of LongChaiJiangXue Formula for Treatment of Polycythemia Vera

Abstract

Background: LongChaiJiangXue formula (LCJX) has the effect of not only clearing up excessive erythrocytes but also relieving clinical symptoms of Polycythemia vera (PV). Material/Methods: The chemical constitution of LCJX was identified from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Seven hundred and fifty-nine targets were identified and a total of 248 targets were screened out after discarding duplication and genes without any ID in databases. GeneCards database, OMIM database, and GEO database were searched for differential expression genes. The network was built by Cytoscape (3.7.2) software and the protein-protein interaction (PPI) networks of PV and LCJX were merged by https://string-db.org . Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment was processed by the R platform. The molecular docking technology was used to further analyze the intense of the assosiation of the compounds and targets. Results: 73 compounds of LCJX were chosen as the candidate active compounds. The compound-targets network contained 105 nods and 216 edges that presented the interaction of agents and targets. The PPI network of LCJX targets involved 59 nodes and 168 edges. The network showed that the key nodes were concentrated in signal transducer and activator of transcription-3(STAT-3), interleukin-6(IL-6), Janus kinase 2(JAK2), and vascular endothelial growth factor-A(VEGFA). The most enriched terms in the GO analysis in the GO biological processes(BP) were reactive oxygen species metabolic process, response to lipopolysaccharide, and response to oxidative stress. According to GO molecular functions(MF), the central nodes were generally enriched in cytokine receptor binding, cytokine activity, and heme binding. Regarding the GO cell components(CC), the terms included vesicle lumen, cytoplasmic vesicle lumen, and secretory granule lumen. In light of the KEGG enrichment analysis, the Hepatitis B, AGE-RAGE signaling pathway in diabetic complications, Kaposi sarcoma-associated herpesvirus infection, measles, Human cytomegalovirus infection, and JAK-STAT signaling pathway were significantly enriched. The molecular docking technology found that puerarin and saikosaponin A had relative stronger affinity with VEGFA, HIF-1A, JAK2 and STAT3 than other compounds in terms of the binding free energy. Conclusions: The effect of LCJX on PV is achieved through a series of complex mechanisms. Network pharmacology and molecular docking are powerful tools to reveal the effect of compound Chinese medicine on the disease.