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.

中文翻译：

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综合生物信息学和网络药理学确定归脾汤治疗抑郁症和胃肠道疾病合并症的机制和分子靶点

背景

归脾汤（GPD）不仅能改善胃肠（GI）功能，还能改善抑郁情绪。生物信息学研究旨在揭示抑郁症和胃肠道疾病之间潜在的串扰基因和相关途径。采用网络药理学方法探索 GPD 同时治疗抑郁症合并胃肠道疾病的分子机制和潜在靶点。

方法

基于GSE98793和GSE19738鉴定重度抑郁症（MDD）的差异表达基因（DEG），并从GeneCards数据库中筛选胃肠道疾病相关基因。获得MDD和胃肠道疾病之间的重叠基因来识别潜在的串扰基因。构建蛋白质-蛋白质相互作用（PPI）网络来筛选枢纽基因，通过LASSO回归分析鉴定特征基因，并进行单样本基因集富集分析（ssGSEA）来分析免疫细胞浸润。此外，基于中药系统药理学（TCMSP）数据库，我们筛选了GPD的活性成分和靶点，并分别确定了GPD与MDD和胃肠道疾病相关基因的交叉靶点。使用 Cytoscape 构建了“成分-目标”网络，并进行了基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 通路分析。

结果

MDD校正数据集包含2619个DEG，总共获得109个串扰基因。筛选出14个中心基因，分别是SOX2、CRP、ACE、LEP、SHH、CDH2、CD34、TNF、EGF、BDNF、FN1、IL10、PPARG和KIT。通过 LASSO 回归分析识别出这些基因的 3 个特征基因，包括 TNF、EGF 和 IL10。γ.delta.T.细胞与所有三个特征基因显着正相关，而Central.memory.CD4.T.细胞和Central.memory.CD8.T.细胞与EGF和TNF显着负相关。GPD包含134个活性成分和248个靶点，其中分别有41个和87个治疗抑郁症和胃肠道疾病的相关靶点。EGF、PPARG、IL10 和 CRP 与该疾病的核心基因重叠。

结论

我们发现GPD可能通过EGF、PPARG、IL10和CRP靶点调节炎症和氧化应激反应，进而参与抑郁症和胃肠道疾病的治疗。