Zhou Qiong, Huang Xiaoman, Chen Zihao, Wang Fuwei, Xie Lihua, Sun Qiang, Du Jikun, Lin Jiantao, Li Baohong, Li Li
Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, The Affiliated Dongguan Songshan Lake Central Hospital, School of Pharmacy, Guangdong Medical University, Dongguan, China.
Dalang Hospital of Dongguan, Dongguan, China.
Brain Res. 2025 May 22;1862:149680. doi: 10.1016/j.brainres.2025.149680.
The therapeutic mechanisms of Rhizoma Polygonati (RP) on Alzheimer's disease (AD) were explored using network pharmacology methods and in vitro experiments for validation.
First, the main active ingredients and target proteins of RP were screened using Traditional Chinese Medicine Systems Pharmacology (TCMSP) and UniProt protein database. AD-related targets were predicted using the DisGeNET database. Subsequently, Protein-protein interaction (PPI) networks and core targets were analyzed using STRING. DAVID was utilized for GO annotation, while KEGG plug-in was employed to perform enrichment analysis of KEGG pathways. AutoDockTools were examined molecular docking. And the RP mechanism on AD was confirmed in vitro experimentation.
Screening identified 8 active ingredients, 76 potential targets, and 3397 CE-related genes, with 58 overlapping targets. 4 target proteins were analyzed through the PPI networks. The RP and AD shared 451 GO biological process items and 150 KEGG signal pathways. Molecular docking results showed that diosgenin (Dio) had strong binding abilities to AKT1 and Caspase 3. Dio inhibited apoptosis through AKT1/Caspase 3 pathway in the glutamate-induced SH-SY5Y cells in vitro.
The study revealed RP's potential mechanisms in treating AD, offering a theoretical basis for clinical use, by integrating network pharmacology with in vitro experiments.
采用网络药理学方法并通过体外实验验证，探讨黄精对阿尔茨海默病（AD）的治疗机制。
首先，利用中药系统药理学（TCMSP）和UniProt蛋白质数据库筛选黄精的主要活性成分和靶蛋白。使用DisGeNET数据库预测AD相关靶点。随后，利用STRING分析蛋白质-蛋白质相互作用（PPI）网络和核心靶点。利用DAVID进行基因本体（GO）注释，同时使用KEGG插件对KEGG通路进行富集分析。使用AutoDockTools进行分子对接。并通过体外实验证实黄精对AD的作用机制。
筛选出8种活性成分、76个潜在靶点和3397个与AD相关的基因，其中有58个重叠靶点。通过PPI网络分析了4个靶蛋白。黄精与AD共有451个GO生物学过程条目和150条KEGG信号通路。分子对接结果表明，薯蓣皂苷元（Dio）与AKT1和半胱天冬酶3具有较强的结合能力。在体外，Dio通过AKT1/半胱天冬酶3通路抑制谷氨酸诱导的SH-SY5Y细胞凋亡。
本研究通过网络药理学与体外实验相结合，揭示了黄精治疗AD的潜在机制，为临床应用提供了理论依据。
