目的 基于GEO数据库基因芯片挖掘与网络药理学,探讨柴胡疏肝散拆分的行气组、解郁组及柴胡疏肝散全方组治疗肝癌共病抑郁的作用机制.方法 通过TCMSP平台获得柴胡疏肝散的潜在活性成分和候选靶点,从GEO数据库下载肝癌和抑郁症的相关基因数据集,药物靶点和疾病靶点取交集,利用STRING数据库对交集靶点进行蛋白互作网络(protein-protein interaction,PPI)分析,筛选核心网络节点,利用Reactome数据库对核心靶点进行通路信息挖掘.结果 共获得行气组交集靶点24个,解郁组交集靶点52个,柴胡疏肝散全方交集靶点57个.筛选出行气组核心靶点9个,解郁组核心靶点20个,柴胡疏肝散全方组核心靶点21个.行气组核心靶点涉及的通路主要为细胞周期、肿瘤蛋白p53(tumor protein p53,TP53)表达的调控、磷脂酰肌醇3-激酶(phosphatidylinositol-3-kinase,PI3K)在癌症中的组成信号传导等.解郁组核心靶点主要通路包括白细胞介素(interleukin,IL)-10的信号传导、细胞周期、TP53调节细胞周期基因的转录、癌基因诱导的细胞衰老、细胞应激反应、氧化应激诱导的细胞衰老等.柴胡疏肝散全方组涉及的通路与解郁组一致.结论 行气组药物可能通过调控细胞周期、细胞增殖、凋亡、自噬、侵袭和迁移来治疗肝癌.解郁组与柴胡疏肝散全方可能通过调节机体"神经-内分泌-免疫"系统,发挥抑制免疫反应、抑制小胶质细胞激活、抑制下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal,HPA)轴激活、抗氧化等作用,从而治疗肝癌合并抑郁.解郁组药物可能是柴胡疏肝散治疗肝癌合并抑郁的核心药物.
Exploration of the Mechanism of Chaihu Shugan San in Treating Comorbid Depression in Liver Cancer Based on Literature Review
Objective Exploring the mechanisms of Chaihu Shugan San in treating liver cancer with depression based on gene chip mining from the GEO database and network pharmacology,focusing on the promoting Qi circulation group,relieving depression group and whole recipe group. Methods Use the TCMSP platform to identify the potential active ingredients and candidate targets of Chaihu Shugan San. Download gene datasets related to liver cancer and depression from the GEO database. Take the intersection of drug targets from different groups and disease genes,conduct protein-protein interaction (PPI) analysis on the intersecting targets using the STRING database,screen for core network nodes,and finally perform pathway information mining on the core targets using the Reactome database. Results A total of 24 intersecting targets were obtained from the promoting Qi circulation group,52 from the relieving depression group,and 57 from the whole formula group. After screening,9 core targets were identified for the promoting Qi circulation group,20 for the relieving depression group,and 21 for the Chaihu Shugan San group. The main pathways associated with the core targets in the promoting Qi circulation group include regulation of the cell cycle,regulation of tumor protein p53 (TP53) expression,and phosphatidylinositol-3-kinase (PI3K) signaling in cancer. The core targets of the relieving depression group mainly involve interleukin-10 signaling,cell cycle,TP53-regulated transcription,induction of cell senescence by oncogenes,cellular stress response,and oxidative stress-induced cell senescence. The whole formula shares similar pathways with the relieving depression group. Conclusion The promoting Qi circulation group may treat liver cancer by regulating the cell cycle,cell proliferation,apoptosis,autophagy,invasion,and migration. The relieving depression group and Chaihu Shugan San may potentially exert their effects in treating liver cancer with depression by modulating the "neuroendocrine-immune" system,inhibiting immune response,suppressing microglial cell activation,inhibiting hypothalamic-pituitary-adrenal (HPA) axis activation,and exhibiting antioxidant properties. The drugs in the relieving depression group potentially serve as core medications when using Chaihu Shugan San for treating this comorbidity.
万方数据
维普
