中医学报2025，Vol.40Issue(5)：1091-1100,10.DOI:10.16368/j.issn.1674-8999.2025.05.176
基于数据挖掘探讨橙皮苷治疗抑郁症的机制及初步实验验证
Mechanism and Preliminary Experimental Validation of Hesperidin in Treatment of Depression Based on Data Mining
摘要
Abstract
Objective:To explore the mechanism of hesperidin in the treatment of depression based on bioinformatics methods,and to conduct preliminary verification through animal experiments.Methods:DisGeNET,Drugbank,GeneCards databases and GSE76826 data-sets were used to screen the targets of depression.Hesperidin targets were retrieved using TCMIP,TCMSP,BATMAN-TCM and Swiss Target Prediction databases.The targets of depression and hesperidin were intersected,and a Wayne diagram was plotted.The STRING database was used to map the protein-protein interaction(PPI)network and screen key targets.The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of key targets was performed using R language,and the key pathways were screened.Molecular docking analysis of hesperidin to key targets was performed by Auto Dock 1.5.6 software.ROC analysis of key targets was performed in R language,and the area under concentration-time curve(AUC)was obtained.Twenty-four SD rats were randomly divided into blank group,model group and hesperidin group(20 mg·kg-1),with8 rats in each group.The chronic restraint method was used to es-tablish a depression model for 21 days.The open field experiment,sugar water preference test and elevated cross maze test were used to evaluate the depressive behavior of rats.Ultra performance liquid chromatography(UPLC)was used to detect norepinephrine(NE),epinephrine(EP),levodopa(L-DOPA),dopamine(DA),5-Serotonin(5-hydroxytryptamine)(5-HT)and homovanillic acid(HVA)content.Results:There were 3850 targets for depression,149 targets for hesperidin,and 83 targets at the intersection of the two.The KEGG pathways involved in the 12 key targets include PI3K/AKT signaling pathway,MAPK signaling pathway and TNF signa-ling pathway.Among them,the PI3K/AKT signaling pathway may be a key pathway for hesperidin in the treatment of depression.The molecular docking binding energy of the five key targets with hesperidin was less than-7.0 kcal·mol-1.ROC analysis showed that TP53 and VEGFA had a higher diagnostic value(AUC>0.900).Compared with the normal group,the central dwell time,the number of penetrations,the number of erections,and the total exercise distance of the model group decreased(P<0.01)and increased after hesperidin treatment(P<0.05).The sugar water preference rate,the percentage of open-arm entry times,and the percentage of open-arm entry time in the model group were lower than those in the normal group and increased after hesperidin treatment(P<0.05).The contents of NE,EP,L-DOPAC,DA,5-HT and HVA in the prefrontal cortex of the model group decreased compared with the normal group and increased after treatment with hesperidin group(P<0.01).Conclusion:Hesperidin may exert antidepressant effect by regu-lating the PI3K/AKT signaling pathway and increasing the content of monoamine neurotransmitters in the prefrontal cortex.关键词
橙皮苷/抑郁症/神经递质/PI3K/AKT信号通路/TP53/VEGFAKey words
hesperidin/depression/neurotransmitters/PI3K/AKT signaling pathway/TP53/VEGFA分类
医药卫生引用本文复制引用
吴永叶,杜志欣,杨丽萍,侯俊林,余晨阳,王昱龙,王钰洁,刘玉娟..基于数据挖掘探讨橙皮苷治疗抑郁症的机制及初步实验验证[J].中医学报,2025,40(5):1091-1100,10.基金项目
国家自然科学基金项目(81973596) （81973596）
河南省大学生创新创业训练计划项目(S202210471038) （S202210471038）
