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基于网络药理学探究四神汤干预伴有抑郁症的腹泻型肠易激综合征的机制
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Abstract:
目的：基于网络药理学和分子对接技术探讨四神汤干预伴有抑郁症(Depression)的腹泻型肠易激综合征(Diarrhea-predominant irritable bowel syndrome, IBS-D)的分子机制。方法：通过TCMSP、GeneCards、TTD、OMIM数据库预测活性成分和疾病靶点；使用Cytoscape 3.10.2软件构建“四神汤–活性成分–潜在靶点–伴有抑郁症的腹泻型肠易激综合征”网络和构建蛋白质相互作用(PPI)网络图；通过R 4.1.1软件进行基因本体(GO)和京东基因与基因组百科全书(KEGG)信号通路富集分析；最后，采用PyMOL 3.0.4和AutoDock 1.5.7软件进行分子对接，验证关键成分与靶点结合的稳定性。结果：筛选出四神汤中24个活性成分和111个干预伴有抑郁症的IBS-D的靶点，GO和KEGG富集分析显示这些靶点与炎症、氧化应激、细胞增殖等生物过程相关，主要涉及磷脂酰肌3–激酶–蛋白激酶B (Phosphatidylinositol 3-kinase-protein kinase B, PI3K-AKT)等信号通路。分子对接数据显示结合能均小于？5 kcal/mol，表明从四神汤中筛选的活性成分与伴有抑郁症的IBS-D的核心靶点有较强的亲和力。结论：四神汤可能通过槲皮素、木犀草素、荷叶碱、薯蓣皂苷元等关键成分作用于白细胞介素-6 (Interleukin-6, IL-6)、丝氨酸/苏氨酸蛋白激酶1 (Akt Serine/Threonine-protein Kinase 1, AKT1)、肿瘤蛋白p53 (Tumor Protein p53, TP53)、5-羟色胺受体2A (5-Hydroxytryptamine Receptor 2A, HTR2A)、5-羟色胺受体3A (5-Hydroxytryptamine Receptor 3A, HTR3A)等核心靶点，与PI3K-AKT和5-羟色胺(5-hydroxytryptamine, 5-HT)等信号通路相关，通过调控炎症、氧化应激、细胞增殖等生物过程干预伴有抑郁症的IBS-D。
Objective: To explore the molecular mechanism of Sishen Decoction in intervening diarrhea-predominant irritable bowel syndrome with depression based on network pharmacology and molecular docking techniques. Methods: Active ingredients and disease targets were predicted by accessing TCMSP, GeneCards, TTD, and OMIM, databases. Next, Cytoscape 3.10.2 software was used to construct the “Sishen Decoction-active ingredients-potential targets-diarrhea-predominant irritable bowel syndrome with depression” network and protein-protein interaction network diagram. R 4.11 software was used to carry out GO and KEGG pathways enrichment analysis. Finally, the above results were validated by molecular docking using PyMOL 3.0.4 and AutoDock 1.5.7 software. Results: 24 active ingredients and 111 targets for intervention in IBS-D with depression were screened out from Sishen Decoction. GO and KEGG analyses showed that these targets were related to biological processes such as inflammation, oxidative stress, and cell proliferation, mainly involving signaling pathways such as phosphatidylinositol PI3K-AKT. Molecular docking data showed that the binding energy was less than ？5 kcal/mol, indicating that the active ingredients screened from Sishen Decoction had a strong affinity with the core targets of IBS-D with depression. Conclusion: Sishen Decoction may exert therapeutic effects through key ingredients including quercetin, luteolin, nuciferine, and diosgenin targeting core proteins such as IL-6, AKT1, TP53, HTR2A
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