目的:探讨阿尔茨海默病(AD)的发病机制,通过网络药理学研究人参皂苷Rg1抗AD的潜在作用靶点和信号通路。PharmMapper,和Uniprot数据库,而GeneCards数据库用于检查淀粉样前体蛋白(APP)和AD的各自靶标。然后,通过Venny工具探索了人参皂苷Rg1和APP之间的共同靶标,活动组件和目标之间的交互网络图是通过Cytoscape软件构建的,以及GO富集和KEGG途径注释分析。此外,GeneCards和FerrDb数据库发现了与铁死亡相关的基因。此外,人参皂苷Rg1、APP、铁性凋亡,并对AD进行了预测和分析。最后,通过免疫组织化学方法评价人参皂苷Rg1和liproxstrain-1对APP/PS1小鼠增殖和分化的影响。结果:人参皂苷Rg1、APP、铁性凋亡,AD有12个hub基因。GO富集和KEGG通路剖析注解,EGFR、SRC,蛋白质水解,蛋白质磷酸化,松弛素途径,FoxO信号通路通过调节APP相关信号通路,在人参皂苷Rg1调控铁凋亡抗AD的潜在机制中起重要作用。APP/PS1小鼠实验证实人参皂苷Rg1和liproxstrain-1可以促进细胞增殖和分化。结论:人参皂苷Rg1、APP和铁细胞凋亡可能作用于EGFR。SRC,松弛素和FoxO信号通路调节蛋白质代谢,蛋白磷酸化等途径改善AD症状。
OBJECTIVE: To explore the pathogenesis of Alzheimer\'s disease (AD), the potential targets and signaling pathways of ginsenoside Rg1 against AD were investigated by network pharmacology.
METHODS: Ginsenoside Rg1 targets were identified through PubChem, PharmMapper, and Uniprot databases, while the GeneCards database was used to examine the respective targets of amyloid precursor protein (APP) and AD. Then, the common targets between ginsenoside Rg1 and APP were explored by the Venny tool, the interaction network diagram between the active components and the targets was built via Cytoscape software, as well as GO enrichment and KEGG pathway annotation analysis were performed. Furthermore, genes associated with ferroptosis were found by the GeneCards and FerrDb databases. Besides, the connection among ginsenoside Rg1, APP, ferroptosis, and AD was predicted and analyzed. Finally, the effects of ginsenosides Rg1 and liproxstain-1 on the proliferation and differentiation of APP/PS1 mice were evaluated by immunohistochemistry.
RESULTS: Ginsenoside Rg1, APP, ferroptosis, and AD had 12 hub genes. GO enrichment and KEGG pathway annotation analysis showed that EGFR, SRC, protein hydrolysis, protein phosphorylation, the Relaxin pathway, and the FoxO signaling pathway play an important role in the potential mechanism of ginsenoside Rg1\'s under regulation of ferroptosis anti-AD through the modulation of APP-related signaling pathways. The APP/PS1 mice experiment verified that ginsenosides Rg1 and liproxstain-1 can promote the proliferation and differentiation.
CONCLUSIONS: Ginsenoside Rg1, APP and ferroptosis may act on EGFR, SRC, the Relaxin and FoxO signaling pathways to regulate protein metabolism, protein phosphorylation and other pathways to improve AD symptoms.