Abstract
Background
Guipi decoction (GPD) not only improves gastrointestinal (GI) function, but also depressive mood. The bioinformatics study aimed to reveal potential crosstalk genes and related pathways between depression and GI disorders. A network pharmacology approach was used to explore the molecular mechanisms and potential targets of GPD for the simultaneous treatment of depression comorbid GI disorders.
Methods
Differentially expressed genes (DEGs) of major depressive disorder (MDD) were identified based on GSE98793 and GSE19738, and GI disorders-related genes were screened from the GeneCards database. Overlapping genes between MDD and GI disorders were obtained to identify potential crosstalk genes. Protein-protein interaction (PPI) network was constructed to screen for hub genes, signature genes were identified by LASSO regression analysis, and single sample gene set enrichment analysis (ssGSEA) was performed to analyze immune cell infiltration. In addition, based on the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, we screened the active ingredients and targets of GPD and identified the intersection targets of GPD with MDD and GI disorder-related genes, respectively. A “component-target” network was constructed using Cytoscape, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed.
Results
The MDD-corrected dataset contained 2619 DEGs, and a total of 109 crosstalk genes were obtained. 14 hub genes were screened, namely SOX2, CRP, ACE, LEP, SHH, CDH2, CD34, TNF, EGF, BDNF, FN1, IL10, PPARG, and KIT. These genes were identified by LASSO regression analysis for 3 signature genes, including TNF, EGF, and IL10. Gamma.delta.T.cell was significantly positively correlated with all three signature genes, while Central.memory.CD4.T.cell and Central.memory.CD8.T.cell were significantly negatively correlated with EGF and TNF. GPD contained 134 active ingredients and 248 targets, with 41 and 87 relevant targets for the treatment of depression and GI disorders, respectively. EGF, PPARG, IL10 and CRP overlap with the hub genes of the disease.
Conclusion
We found that GPD may regulate inflammatory and oxidative stress responses through EGF, PPARG, IL10 and CRP targets, and then be involved in the treatment of both depression and GI disorders.
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Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Code Availability
Custom computer code used in the study is available from the corresponding author upon reasonable request.
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This work was supported by the Scientific Research Projects in Key Areas of Traditional Chinese Medicine of Tianjin Municipal Health and Health Commission (grant number 2023004).
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Huayi Liu and Menglin Liu designed the study. Genhao Fan Performed the operation. Menglin Liu analyzed the data. Menglin Liu and Genhao Fan co-drafted and revised the article. Menglin Liu and Genhao Fan contribution is equal in this work, and it is necessary to consider them as co-first authors.
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Liu, M., Fan, G. & Liu, H. Integrated bioinformatics and network pharmacology identifying the mechanisms and molecular targets of Guipi Decoction for treatment of comorbidity with depression and gastrointestinal disorders. Metab Brain Dis 39, 183–197 (2024). https://doi.org/10.1007/s11011-023-01308-1
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DOI: https://doi.org/10.1007/s11011-023-01308-1