Abstract
Yiqi Shexue formula (YQSX) is traditionally used to treat primary immune thrombocytopenia (ITP) in clinical practice of traditional Chinese medicine. However, its mechanisms of action and molecular targets for treatment of ITP are not clear. The active compounds of YQSX were collected and their targets were identified. ITP-related targets were obtained by analyzing the differential expressed genes between ITP patients and healthy individuals. Protein–protein interaction (PPI) data were then obtained and PPI networks of YQSX putative targets and ITP-related targets were visualized and merged to identify the candidate targets for YQSX against ITP. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out. The gene-pathway network was constructed to screen the key target genes. In total, 177 active compounds and 251 targets of YQSX were identified. Two hundred and thirty differential expressed genes with an P value < 0.005 and |log2(fold change)| > 1 were identified between ITP patient and control groups. One hundred and eighty-three target genes associated with ITP were finally identified. The functional annotations of target genes were found to be related to transcription, cytosol, protein binding, and so on. Twenty-four pathways including cell cycle, estrogen signaling pathway, and MAPK signaling pathway were significantly enriched. MDM2 was the core gene and other several genes including TP53, MAPK1, CDKN1A, MYC, and DDX5 were the key gens in the gene-pathway network of YQSX for treatment of ITP. The results indicated that YQSX’s effects against ITP may relate to regulation of immunological function through the specific biological processes and the related pathways. This study demonstrates the application of network pharmacology in evaluating mechanisms of action and molecular targets of complex herbal formulations.
Highlights
Primary immune thrombocytopenia (ITP) is the most common autoimmune cytopenia characterized by transient or persistent decreased platelet count (Comont et al, 2017; Castro, 2017)
One hundred and forty-eight candidate compounds had a median of 12 degrees, which suggested that most compounds of Yiqi Shexue formula (YQSX) affected multiple targets
Multiple compatible herbs are usually used as complex herbal formulations to improve therapeutic effect through synergism (Li et al, 2016)
Summary
Primary immune thrombocytopenia (ITP) is the most common autoimmune cytopenia characterized by transient or persistent decreased platelet count (Comont et al, 2017; Castro, 2017). The quality of life of ITP patients is affected as a result of the physical and psychological symptoms, discomfort, fear, reduced social activity, and reduced ability to work (López et al, 2015). The standard therapy for newly diagnosed ITP patients is to stop bleeding and increase platelet counts using pharmaceutical medicines (Kühne, 2015). These treatments are often accompanied by harmful side effects, which tend to be more evident with the time of treatment. The high treatment costs cast a heavy financial burden to ITP patients, especially those with severe forms of the disease (Khellaf et al, 2011)
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