基于网络药理学的人参二醇对阿尔茨海默病细胞保护作用的研究  

The study of the protective effect of panoxadiol on Alzheimer's disease cells based on network pharmacology

作　　者：梁喜才 姚璎珈 王玉莹[1] 李秀丽[1] 王雅萌[1] 蔺莹[1] 时悦 杨静娴[1] LIANG Xi-cai;YAO Ying-jia;WANG Yu-ying;LI Xiu-li;WANG Ya-meng;LIN Ying;SHI Yue;YANG Jing-xian(School of Pharmacy,Liaoning University of Traditional Chinese Medicine,Dalian Liaoning 116600,China)

机构地区：[1]辽宁中医药大学药学院,辽宁大连116600

出　　处：《中国药理学通报》2018年第9期1275-1282,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No 81173580)

摘　　要：目的运用网络药理学预测及体外验证方法,研究人参二醇(PD)对阿尔茨海默病(AD)细胞的保护作用。方法运用网络药理学技术,筛选出107个治疗AD的方剂,筛选出现频率最高的人参及其AD作用的靶点,利用分子对接技术,寻找与非受体酪氨酸激酶(FYN)对接评分最高的成分。体外建立APP-N2a细胞模型,采用MTT法检测细胞存活率;LDH方法检测细胞的损伤程度;流式细胞技术检测细胞凋亡及细胞内Ca^(2+)浓度变化情况;Western blot检测磷酸化FYN蛋白表达情况。结果通过网络药理学方法筛选出人参中18个活性成分和29个AD相关靶点,分子对接结果显示,PD与FYN有较强的结合性。实验证明,PD可增加细胞的存活率,降低LDH的释放,且可明显减少细胞凋亡,减轻AD细胞内Ca^(2+)超载,降低FYN-Y416蛋白的表达。结论通过实验验证了网络药理学的预测结果,PD对AD的保护作用可能与抑制FYN磷酸化有关。To explore the therapeutic effects of main active compounds of panaxadiol(PD)in on Alzheimer’s disease(AD)via network pharmacological analysis and Mmolecular docking.Methods A total of 107 prescriptions for AD treatment were screened by using network pharmacology,screening for the highest frequency of ginseng and its target for AD.Use molecular docking technology was used to find components with the highest score for non-receptor tyrosine kinase(FYN)docking.Then we successfully estimatedestablished AD cell model with overexpressinged APP proteins in vitro.Next,the cell viability was detected by MTT assay,the cell damage was detected by LDH assay,the apoptosis and intracellular Ca^2+concentration were detected by flow cytometry,and phosphorylated FYN protein expression was detected by Western blot detection of.phosphorylated FYN protein expression.Results Eighteen active components of Gginseng and 29 AD-related targets were screened by the method of network pharmacology.The results of molecular docking showed that PD had strong binding effects with FYN.The results showed that PD could increase the survival rate of cells,reduce the release of LDH,reduce apoptosis,and improve AD cells’intracellular Ca^2+overload and reduce the expression of FYN-Y416 protein.Conclusion The experimental results of network pharmacology were are verified and the protective effect of PD on AD may be related to inhibition of FYN signaling pathway.

关 键 词：阿尔茨海默病 网络药理学 分子对接 人参二醇 FYN CA^2+超载 

分 类 号：R284.1[医药卫生—中药学] R329.25[医药卫生—中医学]