| 毋肇琪,曹进国.青牛胆对阿尔茨海默病果蝇模型的抗炎与自噬保护作用研究[J].井冈山大学自然版,2025,(5):44-55 |
| 青牛胆对阿尔茨海默病果蝇模型的抗炎与自噬保护作用研究 |
| PROTECTIVE EFFECTS OF TINOSPORA SAGITTATA ON AUTOPHAGY AND ANTI-INFLAMMATION IN DROSOPHILA MODELS OF ALZHEIMER’S DISEASE |
| 投稿时间：2025-01-19 修订日期：2025-03-20 |
| DOI：10.3969/j.issn.1674-8085.2025.05.006 |
| 中文关键词: 青牛胆 阿尔茨海默病 果蝇 抗炎 自噬 |
| 英文关键词: Tinospora sagittata Alzheimer’s disease Drosophila melanogaster anti-inflammatory autophagy |
| 基金项目:国家自然科学基金项目(32160177) |
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| 中文摘要: |
| 本研究采用网络药理学和分子生物学技术，探索青牛胆对阿尔茨海默病果蝇模型的治疗作用。利用UPLC结合文献分析获取青牛胆的主要化学成分；分别通过PubChem和GeneCards数据库来筛选青牛胆主要化学成分，用于治疗阿尔茨海默病的潜在靶点；利用功能蛋白关联（STRING）网络进行蛋白质相互作用（PPI）分析筛选关键靶点；采用DAVID 2021数据库分析其参与的生物学过程及通路；利用行为学和分子生物学实验进行验证。实验结果显示青牛胆有54个主要化学成分，1 078个作用靶点，阿尔茨海默病靶点2 385个，交集结果得到404个交集靶点。GO功能富集分析获得1 771项目，包括1 327个生物过程（BP）、169个细胞组分（CC）和275个分子功能（MF）,KEGG通路富集分析得到了189个途径。筛选出青牛胆抗阿尔茨海默病的核心靶点有PIK3CA、PIK3CB、EGFR等。分子生物学实验结果表明，青牛胆能够下调核心靶点PIK3CA和PIK3CB的表达，并且通过抑制AKT/mTOR信号通路促进自噬，降低NF-κB和炎症因子IL-2、IL-6的水平，进而发挥抗阿尔茨海默病的作用。本研究为青牛胆在阿尔茨海默病的治疗应用方面提供了理论基础，也为利用果蝇模型建立快速筛选和验证抗阿尔茨海默病天然药物的平台提供了新的思路。 |
| 英文摘要: |
| The network pharmacology and molecular biology techniques were employed to investigate the therapeutic effects of Tinospora sagittata（TS） in a Drosophila model of Alzheimer’s disease（AD）.Ultra-performance liquid chromatography（UPLC） analysis combined with extensive literature review was used to identify the main chemical components of TS. Targets related to TS components and AD were screened using the Pub Chem and Gene Cards databases, respectively. Protein-protein interaction（PPI）analysis was performed using the STRING database to identify key targets. The DAVID 2021 database was utilized to analyze the biological processes and pathways involved. Behavioral and molecular experiments were conducted for validation. The results showed that TS contains 54 main active components, 1,078 potential targets, and 2,385 AD-related targets, with 404 overlapping genes identified. Gene Ontology（GO）functional enrichment analysis revealed 1,771 items, including 1,327 biological processes（BP）, 169 cellular components（CC）, and 275 molecular functions（MF）. Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment analysis identified 189 pathways. Core targets of TS against AD, such as PIK3CA,PIK3CB, and EGFR, were screened. Western blot analysis confirmed that TS downregulated the expression of core targets PIK3CA and PIK3CB, promoted autophagy by inhibiting the AKT/m TOR signaling pathway,and reduced the levels of NF-κB and inflammatory factors IL-2 and IL-6, thereby exerting anti-AD effects.This study provides a theoretical foundation for the application of TS in the treatment of Alzheimer’s disease and offers new insights into the rapid screening and validation of anti-AD natural drugs using the Drosophila model. |
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