Tianjin University of Chinese Medicine, Tianjin, China.
Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China.
Metab Brain Dis. 2024 Jan;39(1):183-197. doi: 10.1007/s11011-023-01308-1. Epub 2023 Oct 17.
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.
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.
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.
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.
归芪汤（GPD）不仅能改善胃肠道（GI）功能，还能改善抑郁情绪。本生物信息学研究旨在揭示抑郁和 GI 障碍之间的潜在相互作用基因和相关途径。采用网络药理学方法探讨 GPD 同时治疗抑郁合并 GI 障碍的分子机制和潜在靶点。
基于 GSE98793 和 GSE19738 鉴定重度抑郁症（MDD）的差异表达基因（DEGs），并从 GeneCards 数据库筛选与 GI 障碍相关的基因。获取 MDD 和 GI 障碍之间的重叠基因，以鉴定潜在的相互作用基因。构建蛋白质-蛋白质相互作用（PPI）网络筛选枢纽基因，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）分析免疫细胞浸润。此外，基于中药系统药理学（TCMSP）数据库筛选 GPD 的活性成分和靶点，并分别鉴定 GPD 与 MDD 和 GI 障碍相关基因的交集靶点。使用 Cytoscape 构建“成分-靶点”网络，进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析。
MDD 校正数据集包含 2619 个 DEGs，共获得 109 个相互作用基因。筛选出 14 个枢纽基因，即 SOX2、CRP、ACE、LEP、SHH、CDH2、CD34、TNF、EGF、BDNF、FN1、IL10、PPARG 和 KIT。通过 LASSO 回归分析，这 3 个特征基因分别为 TNF、EGF 和 IL10。Gamma.delta.T.cell 与所有 3 个特征基因均呈显著正相关，而 Central.memory.CD4.T.cell 和 Central.memory.CD8.T.cell 与 EGF 和 TNF 呈显著负相关。GPD 含有 134 种活性成分和 248 个靶点，分别有 41 个和 87 个靶点与治疗抑郁和 GI 障碍相关。EGF、PPARG、IL10 和 CRP 与疾病的枢纽基因重叠。
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，从而参与抑郁和 GI 障碍的治疗。
