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目的：研究原儿茶酸（protocatechuic acid,PCA）抗抑郁症的作用，运用网络药理学和实验验证等方法探究其治疗抑郁症的潜在作用。方法：本研究通过使用SwissTargetPrediction和PharmMapper数据库获得PCA的靶点基因；利用GeneCards、OMIM和DisGenet数据库获取与抑郁症相关的疾病靶点基因。运用R-studio对共有靶点进行基因本体（GO）和信号通路（KEGG）富集分析，应用STRING 12.0在线数据库构建共有靶点蛋白互作网络。运用分子对接观察PCA（配体）与核心靶点（受体）的结合能力。利用动物实验来检测其行为学变化，评价PCA改善抑郁症的功效。结果：网络药理学分析结果显示，ALB、AKT1、HSP90AA1、MMP9、MAPK8等因子作为PCA改善抑郁症的核心靶点，KEGG主要富集在与代谢性疾病、脂质与动脉粥样硬化相关的信号通路上。分子对接结果也显示PCA与抑郁症的核心靶点有较高的结合能力。动物实验显示PCA可以有效改善动物的行为学来治疗抑郁症。结论：PCA可能通过调节ALB、AKT1、HSP90AA1、MMP9、MAPK8等因子和与代谢性疾病、脂质与动脉粥样硬化信号通路来改善抑郁症，对抑郁症具有明显效果。
Abstract：Objective: To study the anti-depression effect of protocatechuic acid(PCA) and explore its potential role in the treatment of depression by network pharmacology and experimental verification. Methods: PCA target gene were obtained by using SwissTargetPrediction and PharmMapper database. Disease target genes associated with depression were obtained from GeneCards, OMIM, and DisGenet databases. R-studio was used to enrich gene ontology(GO) and signaling pathway(KEGG) for common targets, and STRING 12.0 online database was used to construct common target protein interaction network. Molecular docking was used to observe the binding ability of PCA(ligand) to the core target(receptor). Animal experiments were used to detect behavioral changes and evaluate the efficacy of PCA in improving depression. Results: The results of network pharmacological analysis showed that ALB, AKT1, HSP90AA1, MMP9, MAPK8, and other factors were the core targets of PCA to improve depression, and KEGG was mainly concentrated in the signaling pathways related to metabolic diseases, lipids, and atherosclerosis. Molecular docking results also showed that PCA has a high binding ability to the core targets of depression. Animal experiments have shown that PCA can effectively improve the behavior of animals to treat depression. Conclusion: PCA may ameliorate depression by regulating ALB, AKT1, HSP90AA1, MMP9, MAPK8, and metabolic disease, lipid, and atherosclerotic signaling pathways, and has obvious effect on depression.
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基本信息:
DOI：10.13210/j.cnki.jhmu.20241204.002
中图分类号:R285.5
引用信息:
[1]高振杰,张晶,张大伟,等.应用网络药理学和实验验证方法探讨原儿茶酸抗抑郁症的作用机制[J].海南医科大学学报,2025,31(10):758-770.DOI:10.13210/j.cnki.jhmu.20241204.002.
基金信息:
海南医科大学创新创业项目（X202211810077）; 海南省自然科学基金高层次人才项目（820RC624）~~
2024-12-04
2024-12-04
2024-12-04