中国医学科学院学报2026，Vol.48Issue(4)：618-630,13.DOI:10.3881/j.issn.1000-503X.17127
中药复方YA3D3改善APP/PS1转基因小鼠阿尔茨海默病样病理及认知功能
Traditional Chinese Herbal Formula YA3D3 Ameliorates Alzheimer's Disease-Like Pathology and Cognitive Impairment in APP/PS1 Transgenic Mice
摘要
Abstract
Objective To evaluate the effects of the traditional Chinese herbal formula YA3D3 on cog-nitive impairment and cerebral β-amyloid(Aβ)deposition in APP/PS1 transgenic mice and to determine whether these effects are mediated by up-regulation of the autophagy-related gene 14(ATG14).Methods Network phar-macology was employed to predict YA3D3 targets.Total antioxidant capacity and hydroxyl free radical scavenging activity were measured in vitro.BV2 microglial cells were infected with short hairpin RNA(shRNA)lentivirus targeting ATG14(designated as sh-ATG14)and then treated with 0.5 mg/mL of either water-extract(YA3D3-HF)or fermented(YA3D3-MHF)preparation for 24 h.The expression levels of ATG14 and downstream ATG16L1 were assessed by qPCR and Western blot.Sixty-four 3-month-old male APP/PS1 mice were randomly allocated to eight groups(n=8):APP/PS1 model,donepezil,low-,medium-,and high-dose YA3D3-HF,and low-,medium-,and high-dose YA3D3-MHF.All the drugs were administered ad libitum in drinking water for 90 days.Spatial learning and memory were evaluated through the Morris water maze.Cerebral Aβ deposition was quantified by immunofluorescence.Autophagy-related gene expression in the brain tissue was analyzed by qPCR.Results Network pharmacology indicated significant enrichment of YA3D3 targets in autophagy and phosphati-dylinositol 3-kinase/protein kinase B signaling pathways.YA3D3-MHF showed stronger antioxidant activity than YA3D3-HF in vitro(P<0.001).In BV2 cells,both preparations reversed ATG14 knock-down-induced down-regulation in the expression of ATG14 and ATG16L1,with YA3D3-MHF being more potent(P=0.003).The animal experiment showed that all the YA3D3 groups exhibited shorter escape latency and more platform crossings than the APP/PS1 model group(all P<0.05),along with reduced Aβ fluorescence intensity(all P<0.001).The efficacy of high-dose YA3D3-MHF was similar to that of donepezil.qPCR confirmed that YA3D3 up-regulated the expression of ATG14 and modulated the expression of downstream autophagy-related genes in the brain tissue(all P<0.05).Conclusions The traditional Chinese herbal formula YA3D3 may up-regulate the expression of ATG14 to slow down Aβ deposition and ameliorate cognitive impairment in APP/PS1 mice,serving as a potential candidate for Alzheimer's disease intervention.It should be noted that this study has not directly verified the necessity of ATG14 in vivo,and the causal relationship between the in vivo therapeutic efficacy of YA3D3 and the up-regula-tion of ATG14 requires further confirmation.In addition,this study only verifies the expression regulation of auto-phagy-related molecules and does not confirm the enhancement of autophagy flux.关键词
阿尔茨海默病/中药组方/ATG14/β淀粉样蛋白/微生物发酵Key words
Alzheimer's disease/traditional Chinese herbal formula/ATG14/β-amyloid peptide/microbial fermentation分类
医药卫生引用本文复制引用
杨甜,马佳蕊,梁厶爻,张悦萌,郭玲,栗午娟,吕玉红..中药复方YA3D3改善APP/PS1转基因小鼠阿尔茨海默病样病理及认知功能[J].中国医学科学院学报,2026,48(4):618-630,13.基金项目
咸阳市科技局项目(L2025-ZDYF-ZYY-019)、延安市科技局项目(2024-SFGG-201)、大学生创新创业训练计划项目(202410719056)和延安大学研究项目计划(2023KXJ-012、2023CGZH-001) （L2025-ZDYF-ZYY-019）
