浙江大学学报（医学版）2026，Vol.55Issue(5)：414-424,11.DOI:10.3724/zdxbyxb-2025-0661
左归丸关键活性成分槲皮素可通过PI3K/Akt信号通路干预阿尔茨海默病模型细胞
Quercetin,a key bioactive component of Zuogui Pill,protects against Alzheimer's disease by regulating the PI3K/Akt signaling pathway
摘要
Abstract
Objective:To investigate the protective mechanism of quercetin,a key bioactive component of Chinese medicine Zuogui Pill,against Alzheimer's disease(AD)via the PI3K/Akt signaling pathway.Methods:The TCMSP,PubChem,SwissTargetPrediction,and BATMAN-TCM databases were used to retrieve the active components of Zuogui Pill and predict their potential targets.Target information was standardized using the UniProt database.AD-related target genes were obtained from DrugBank,GeneCards,and OMIM,and the intersection was taken to identify the potential targets of Zuogui Pill for AD treatment.Based on these targets,a protein-protein interaction network was constructed using Cytoscape 3.10.1 and the STRING database.The key active components and core targets of Zuogui Pill for AD treatment were identified through computational analysis.Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed on the potential targets to explore the biological processes and signaling pathways involved.Subsequently,molecular docking and binding affinity prediction between the key active component quercetin and the core target Akt1 were performed using the online tool CB-Dock2.An AD cell model was established by treating mouse hippocampal neuron cells(HT22)with amyloid β-protein1-42(Aβ1-42)oligomers.The cells were divided into low-,medium-,and high-dose quercetin groups,and a PI3K agonist(EGF)group for in vitro experiments.To verify whether quercetin exerts its anti-apoptotic effects by regulating the PI3K/Akt pathway,additional groups were established:PI3K inhibitor(LY294002)group,PI3K inhibitor+high-dose quercetin group,and PI3K inhibitor+EGF group.CCK-8 assay was used to detect cell viability;JC-1,Calcein-AM/PI,and Hoechst staining were used to assess apoptosis;and Western blotting was used to detect expression of PI3K/Akt signaling pathway and apoptosis related proteins.Results:Network pharmacology demonstrated that quercetin targets core proteins such as Akt1 in a network manner and is predominantly enriched in the PI3K/Akt signaling pathway.Molecular docking showed favorable binding affinity between quercetin and Akt1(binding energy:-6.6 kcal/mol).In the Aβ1-42 oligomer-induced HT22 neuronal cell model and HT22 cells treated by PI3K inhibitor,high-dose quercetin significantly increased cell viability,elevated the p-Akt/Akt ratio and Bcl-2 expression level(all P<0.05),reduced the cleaved caspase-3/caspase-3 ratio as well as the expression levels of BAX and cytochrome C(all P<0.01),and alleviated apoptosis of HT22 cells.Conclusion:Quercetin,a key bioactive component of Chinese medicine Zuogui Pill,inhibits neuronal apoptosis by regulating the PI3K/Akt signaling pathway,thereby exerting a protective effect against AD.关键词
阿尔茨海默病/左归丸/槲皮素/细胞凋亡/网络药理学/PI3K/Akt信号通路/体外实验/HT22细胞Key words
Alzheimer's disease/Zuogui Pill/Quercetin/Apoptosis/Network phar-macology/PI3K/Akt signaling pathway/In vitro experiment/HT22 cell分类
医药卫生引用本文复制引用
李光亚,李沛泽,黄柳玲,朱静文,秦秀德,陆韵薇..左归丸关键活性成分槲皮素可通过PI3K/Akt信号通路干预阿尔茨海默病模型细胞[J].浙江大学学报（医学版）,2026,55(5):414-424,11.基金项目
国家自然科学基金(82405265) （82405265）
广东省基础与应用基础研究基金(2023A1515110832) （2023A1515110832）
深圳市科技计划(JCYJ20230807094801002) （JCYJ20230807094801002）
深圳市中医院"3030计划"中医临床研究项目(G3030202101)This study was supported by National Natural Science Foundation of China(82405265),Guangdong Basic and Applied Basic Research Foundation(2023A1515110832),Shenzhen Science and Technology Program(JCYJ20230807094801002),and"3030 Plan"TCM Clinical Research Project of Shenzhen Traditional Chinese Medicine Hospital(G3030202101). （G3030202101）
