Zhiyan Chen, Min Zhan, Yida Du, Chunying He, Xiaohua Hu, Yutong Li, Huan Wang, Linjuan Sun
Graduate School of Beijing University of Chinese Medicine, Beijing, China.
Department of Neurology, China Academy of Chinese Medical Sciences Xiyuan Hospital, Beijing, China.
Front Pharmacol. 2024 Aug 16;15:1424803. doi: 10.3389/fphar.2024.1424803. eCollection 2024.
Pathological changes in the central nervous system (CNS) begin before the clinical symptoms of Alzheimer's Disease (AD) manifest, with the hippocampus being one of the first affected structures. Current treatments fail to alter AD progression. Traditional Chinese medicine (TCM) has shown potential in improving AD pathology through multi-target mechanisms. This study investigates pathological changes in AD hippocampal tissue and explores TCM active components that may alleviate these changes.
GSE5281 and GSE173955 datasets were downloaded from GEO and normalized to identify differentially expressed genes (DEGs). Key functional modules and hub genes were analyzed using Cytoscape and R. Active TCM components were identified from literature and the Pharmacopoeia of the People's Republic of China. Enrichment analyses were performed on target genes overlapping with DEGs.
From the datasets, 76 upregulated and 363 downregulated genes were identified. Hub genes included SLAMF, CD34, ELN (upregulated) and ATP5F1B, VDAC1, VDAC2, HSPA8, ATP5F1C, PDHA1, UBB, SNCA, YWHAZ, PGK1 (downregulated). Literature review identified 33 active components from 23 herbal medicines. Target gene enrichment and analysis were performed for six components: dihydroartemisinin, berberine, naringenin, calycosin, echinacoside, and icariside II.
Mitochondrial to synaptic vesicle dysfunction pathways were enriched in downregulated genes. Despite downregulation, UBB and SNCA proteins accumulate in AD brains. TCM studies suggest curcumin and echinacoside may improve hippocampal pathology and cognitive impairment in AD. Further investigation into their mechanisms is needed.
中枢神经系统（CNS）的病理变化在阿尔茨海默病（AD）临床症状出现之前就已开始，海马体是最早受影响的结构之一。目前的治疗方法无法改变AD的病程。中药已显示出通过多靶点机制改善AD病理的潜力。本研究调查AD海马组织的病理变化，并探索可能减轻这些变化的中药活性成分。
从基因表达综合数据库（GEO）下载GSE5281和GSE173955数据集并进行标准化，以识别差异表达基因（DEG）。使用Cytoscape和R分析关键功能模块和枢纽基因。从文献和《中华人民共和国药典》中鉴定中药活性成分。对与DEG重叠的靶基因进行富集分析。
从数据集中鉴定出76个上调基因和363个下调基因。枢纽基因包括信号淋巴细胞激活分子家族（SLAMF）、CD34、弹性蛋白（ELN）（上调）和ATP合酶F1亚基β（ATP5F1B）、电压依赖性阴离子通道1（VDAC1）、电压依赖性阴离子通道2（VDAC2）、热休克蛋白家族A成员8（HSPA8）、ATP合酶F1亚基C（ATP5F1C）、丙酮酸脱氢酶E1α亚基（PDHA1）、泛素B（UBB）、α-突触核蛋白（SNCA）、14-3-3蛋白ζ（YWHAZ）、磷酸甘油酸激酶1（PGK1）（下调）。文献综述从23种草药中鉴定出33种活性成分。对二氢青蒿素、黄连素、柚皮素、毛蕊异黄酮、紫锥菊苷和淫羊藿苷II这六种成分进行了靶基因富集和分析。
下调基因中富集了线粒体到突触小泡功能障碍途径。尽管UBB和SNCA蛋白下调，但它们在AD大脑中积累。中药研究表明，姜黄素和紫锥菊苷可能改善AD的海马病理和认知障碍。需要进一步研究它们的作用机制。
