Exploring the interventional effects of isochlorogenic acid A on Alzheimer's disease based on network pharmacology and cellular experiments
HAO Feng-xiao
ZENG Meng-nan
CAO Bing
LIANG Xi-wen
YE Kai-li
FENG Wei-sheng
ZHENG Xiao-ke
Abstract：Objective:To investigate the mechanism of action of isochlorogenic acid A(IAA)in intervening in Alzheimer's disease(AD)and validate the mechanism using cellular experiments.Methods:IAA and AD targets were obtained from network pharmacology databases,"drug-disease"network diagrams were constructed,GO biological process enrichment and KEGG pathway enrichment analyses were performed on the screened out intersecting targets,and molecular docking was performed on the core targets.Aβ25～35-induced highly differentiated PC12(PC12-H)and N9 cells were used to construct AD cell models,and cell viability,apoptosis,ROS,mRNA levels of key targets and pathway-related proteins were detected.Results:Network pharmacology identified 23 targets for IAA intervention in AD,which are related to signaling pathways such as MAPK and EGFR/Ras/ERK.Molecular docking showed strong affinity of IAA to the core target proteins APP,EGFR,KDR,and BACE1.Cell culture experiments showed that IAA significantly enhanced the viability of Aβ25～35-induced PC12-H and N9 cells,and decreased the levels of apoptosis-related proteins and mRNA in the cells;meanwhile,it decreased the mRNA levels of EGFR,APP and BACE1 in the cells,and regulated the expression of EGFR/Ras/ERK pathway-related proteins.Conclusion:Network pharmacological analysis showed that the effects of IAA on AD involve APP,EGFR,KDR,BACE1 and other targets;cellular experiments indicated that the mechanism of IAA intervention in AD is related to activation of the EGFR/Ras/ERK pathway to inhibit apoptosis.
Keywords：isochlorogenic acid AAlzheimer's diseaseEGFR/Ras/ERK pathwayapoptosis
Publication Date：2025-01-29
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：10( 173-182 )