目的 整合网络药理学、分子对接技术和实验验证，系统探讨青娥丸治疗阿尔茨海默病（AD）的潜在活性成分及其作用机制。方法 经过ETCM数据库、TCMSP数据库及文献搜索通过SWISS ADME平台和Swiss Target Prediction数据库筛选出青娥丸主要活性成分及靶点，通过GeneCards数据库和OMIM数据库获取AD靶点；取交集靶点后用STRING数据库构建青娥丸治疗AD潜在靶点的蛋白质–蛋白质相互作用（PPI）。运用Cytoscape 3.9.1软件筛选核心靶点；采用DAVID数据库对交集靶点进行基因本体（GO）功能富集分析及京都基因与基因组百科全书（KEGG）通路富集分析。使用PyMol软件和AutoDock1.5.7软件进行分子对接验证。建立HT22细胞模型，采用CCK-8法检测细胞活力，通过Western blotting检测磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）通路和细胞凋亡的关键作用靶点蛋白表达水平。结果 共得到青娥丸活性成分119个，靶点900个；疾病靶点1 409个。PPI网络获得核心靶点Akt1、非受体酪氨酸激酶（SRC）、热休克蛋白90α家族A类成员1（HSP90AA1）、肿瘤坏死因子（TNF）和表皮生长因子受体（EGFR）等。GO和KEGG富集分析获得1 532个GO功能注释，192条信号通路，主要涉及PI3K/Akt通路、细胞凋亡等。分子对接结果显示，青娥丸中的主要活性成分与关键靶点均有强的结合能力，对接结合能均低于−6.0 kcal/mol。细胞实验表明，与对照组比较，青娥丸可以改善Aβ25-35诱导的HT22细胞活力（P＜0.01），提高Aβ25-35诱导的HT22细胞中p-Akt、p-PI3K和Bcl-2蛋白的表达，抑制Bax蛋白的表达（P＜0.05）。结论 青娥丸可能通过调节PI3K/Akt信号通路和细胞凋亡保护神经元，延缓病理进程治疗AD，为青娥丸的临床应用和AD治疗的研究提供依据。

Objective Integrate network pharmacology, molecular docking technology and experimental verification to systematically explore the potential active ingredients and mechanisms of Qing’e Pills in treating Alzheimer′s disease (AD).Methods The main active components and targets of Qing’e Pills were screened using the ETCM database, TCMSP database, and literature search via the SWISS ADME platform and Swiss Target Prediction database. AD-related targets were obtained from the Gene Cards database and OMIM database. Intersection targets were identified, and the STRING database was used to construct a protein-protein interaction (PPI) network of potential targets for Qing’e Pills in treating AD. Core targets were screened using Cytoscape 3.9.1 software. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the intersection targets were performed using the DAVID database. Molecular docking validation was conducted using PyMol software and Auto Dock 1.5.7 software. An HT22 cell model was established, and cell viability was assessed using the CCK8 assay. Western blotting was used to detect the expression levels of key target proteins in the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway and apoptosis.Results A total of 119 active components and 900 targets of Qing′e Pills were identified, along with 1 409 disease-related targets. The PPI network revealed core targets such as Akt1, non-receptor tyrosine kinase (SRC), heat shock protein 90 alpha family class A member 1 (HSP90AA1), tumor necrosis factor (TNF), and epidermal growth factor receptor (EGFR). GO and KEGG enrichment analysis yielded 1 532 GO functional annotations and 192 signaling pathways, primarily involving the PI3K/Akt pathway and apoptosis. Molecular docking results demonstrated that the main active components of Qing′e Pills exhibited strong binding affinities to the key targets, with docking binding energies all below −6.0 kcal/mol. Cell experiments showed that, compared to the control group, Qing’e Pills significantly improved Aβ25-35-induced HT22 cell viability (P < 0.01), increased the expression of p-Akt, p-PI3K, and Bcl2 proteins in Aβ25-35-induced HT22 cells, and inhibited the expression of Bax protein (P < 0.05).Conclusion Qing’e Pills may protect neurons and delay the pathological process of AD by regulating the PI3K/Akt signaling pathway and apoptosis, which provides a basis for the clinical application of Qing′e Pills and the research of AD treatment.

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中国博士后（54批）科学基金项目（2013M541427）