摘要
目的通过网络药理学、分子对接和动物实验验证的方法,探讨中药肉苁蓉治疗阿尔茨海默病(AD)的作用机制。方法依据中药系统药理数据库与分析平台挖掘肉苁蓉有效成分,并通过SwissTargetPrediction、DisGeNET和GeneCards数据库筛选出肉苁蓉和AD相关靶标,并对两者交集靶点进行蛋白相互作用网络(PPI)分析。通过Metascape数据库进行京都基因与基因组百科全书(KEGG)通路富集分析;利用AutoDock Vina对肉苁蓉有效成分与核心靶点进行分子对接;在网络药理学预测基础上,采用8月龄SAMP8系小鼠建立AD模型,通过Morris水迷宫测试小鼠学习认知功能,尼氏染色观测小鼠海马神经元形态,ELISA、Western blot实验检测小鼠海马组织中cAMP信号通路相关蛋白表达水平。结果基于网络药理学分析预测,肉苁蓉可能通过8种活性成分作用于74个AD靶点。分子对接结果显示毛蕊花糖苷等活性成分与ESR1、BDNF、MAPK1、APP等核心靶点具有较高亲和力。KEGG结果分析主要涉及癌症的通路、cAMP信号通路、AD通路等。动物实验结果表明,肉苁蓉能有效改善AD小鼠的学习认知功能障碍,改善小鼠海马神经元损伤。ELISA、Western blot实验结果表明,肉苁蓉能显著提高cAMP通路cAMP、PKA、P-CREB蛋白表达水平,并促进下游神经营养因子BDNF蛋白的表达。结论肉苁蓉可以改善AD模型小鼠学习认知障碍,并且可能通过上调cAMP信号通路及下游BDNF蛋白靶点的表达,改善海马神经元损伤而发挥治疗AD的作用。
Objective To explore the mechanism of cistanche deserticola(meat cistanche)in treating Alzheimer′s disease(AD)through network pharmacology,molecular docking,and animal experiments.Methods Effective components of meat cistanche were mined from the TCMSP database,and AD-related targets were filtered using the SwissTargetPrediction,DisGeNET,and GeneCards databases.The intersection of these targets was analyzed using protein-protein interaction(PPI)networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted via the Metascape database.Molecular docking of meat cistanche′s active components with core targets was performed using AutoDock Vina.Based on network pharmacology predictions,an AD model was established using 8-month-old SAMP8 mice,with Morris water maze tests assessing learning and cognitive functions,Nissl staining observing hippocampal neuron morphology,and enzyme-linked immunosorbent assays and Western blotting detecting the expression levels of cAMP signaling pathway-related proteins in hippocampal tissues.Results Network pharmacology analysis predicted that meat cistanche might act on 74 AD targets through 8 active components.Molecular docking showed high affinity of active components like acteoside with core targets such as ESR1,BDNF,MAPK1,and APP.KEGG analysis indicated involvement in pathways related to cancer,cAMP signaling,and AD.Animal experiments demonstrated that meat cistanche effectively improved learning and cognitive impairments in AD mice and alleviated hippocampal neuron damage.ELISA and Western blotting results indicated that meat cistanche significantly increased the expression levels of cAMP,PKA,P-CREB in the cAMP pathway and promoted the expression of downstream neurotrophic factor BDNF.Conclusion Meat cistanche can improve learning and cognitive disorders in AD model mice and may exert therapeutic effects on AD by up-regulating the cAMP signaling pathway and the expression of downstream BDNF protein targets,thereby improving hippocampal neuron injury.
作者
赵杰
霍东升
祝洪博
张士滨
贾建新
Zhao Jie;Huo Dongsheng;Zhu Hongbo;Zhang Shibin;Jia Jianxin(School of Basic Medicine and Forensic Science,Baotou Medical College of Inner Mongolia University,Baotou 014040;Dept of Human Anatomy,Baotou Medical College of Inner Mongolia University,Baotou 014040)
出处
《安徽医科大学学报》
北大核心
2025年第7期1266-1274,共9页
Acta Universitatis Medicinalis Anhui
基金
国家自然科学基金(编号:81860215)
内蒙古自治区高等教育青年科技人才支持计划(编号:NJYT-20-A08)。
