基于网络药理学和分子对接技术研究八珍益智方治疗阿尔茨海默病的潜在作用机制

夏玲; 郭盛; 钱大玮; 武文星; 卜凡淑; 朱悦; 赵明; 牛阳; 段金廒

基于网络药理学和分子对接技术研究八珍益智方治疗阿尔茨海默病的潜在作用机制

1.
南京中医药大学江苏省中药资源产业化过程协同创新中心/中药资源产业化与方剂创新药物国家地方联合工程研究中心/江苏省方剂高技术研究重点实验室，江苏南京 210023
2.
宁夏医科大学中医药现代化教育部重点实验室，宁夏银川 750021

计量
- 文章访问数: 652
- HTML全文浏览量: 46
- PDF下载量: 544
- 被引次数: 0
出版历程
- 刊出日期: 2020-11-10

Exploration on the Mechanism of Bazhen Yizhi Prescription in Treating Alzheimer's Disease Based on Network Pharmacology and Molecular Docking

1.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China
2.
Key Laboratory of Ministry of Education for Chinese Medicine Modernization, Ningxia Medical University, Yinchuan, 750021, China

摘要

摘要: 目的利用网络药理学方法及分子对接技术，研究八珍益智方治疗阿尔茨海默病（Alzheimer's disease，AD）的潜在药效物质基础和作用机制，为其临床应用提供理论依据。方法通过TCMSP、BATMAN-TCM、TCMID、中国知网（CNKI）和Pubmed数据库检索八珍益智方8味组方药材化学成分和作用靶点；通过GeneCards、OMIM数据库查询AD的相关靶点；利用R语言3.6.3得到药物和疾病的交集靶点；借助String数据库和Cytoscape 3.7.2软件构建PPI网络，筛选核心靶点；通过DAVID数据库进行GO功能富集分析和KEGG通路富集分析；利用AutoDock tools 1.5.6、AutoDock vina 1.1.2进行分子对接。结果八珍益智方共收集到200个化学成分和226个靶点，Cytoscape 3.7.2软件筛选出包括AKT1、MAPK3、IL-6、VEGFA、CASP3等37个核心靶点，槲皮素、山柰酚、柚皮苷、豆甾醇、7-甲氧基-2-甲基异黄酮等15个核心化合物。GO富集分析得到1 331个条目（P<0.05），KEGG通路富集得到相关通路65条（P<0.05）。分子对接结果显示15个核心化合物和AKT1、MAPK3、IL-6、VEGFA、CASP3具有较好的亲和力。结论八珍益智方治疗AD的通路主要涉及癌症的途径、MAPK信号通路、前列腺癌、神经活性配体-受体相互作用、钙信号通路等，研究结果为八珍益智方治疗AD作用机制的进一步阐明提供了指引。
- 八珍益智方 /
- 阿尔茨海默病 /
- 网络药理学 /
- 分子对接技术
Abstract: OBJECTIVE To provide a theoretical basis for the clinical application of Bazhen Yizhi Prescription (BZYZP)， an exploration of the potential mechanism of BZYZP in the treatment of Alzheimer's disease (AD) was performed using network pharmacology and molecular docking. METHODS TCMSP， BATMAN-TCM， TCMID， CNKI and Pubmed database were used to search the compounds and the targets of BZYZP. The AD-related targets were screened by the GeneCards and OMIM databases. R3.6.3 was applied to get the cross targets between drugs and disease. PPI network was constructed by String database and Cytoscape 3.7.2， the core targets were screened. Gene ontology (GO) functional enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID. AutoDock tools 1.5.6 and AutoDock Vina 1.1.2 were used for Molecular docking. RESULTS Total of 200 active components were screened from BZYZP， corresponding to 226 targets. Among them， there were 37 core targets including AKT1， MAPK3， IL-6， VEGFA， and CASP3， and 15 core compounds， such as quercetin， kaempferol， naringin， stigmasterol， 7-methoxy-2-methyl isoflavone. Total 1 331 (P<0.05) and 65 pathways (P<0.05) were obtained by GO analysis and KEGG analysis. The results of molecular docking showed that 15 core compounds had a good affinity with AKT1， MAPK3， IL-6， VEGFA and CASP3. CONCLUSION The pathways of BZYZP in the treatment of AD mainly involve the pathway of cancer， MAPK signal pathway， prostate cancer， neuroactive ligand-receptor interaction， calcium signal pathway. The results of this study may guide the elucidation of the mechanism of BZYZP in the treatment of AD.
- Bazhen Yizhi Prescription /
- Alzheimer's disease /
- network pharmacology /
- molecular docking

HTML全文

参考文献(24)

[1]	RAJASEKHAR K，GOVINDARAJU T．Current progress，challenges and future prospects of diagnostic and therapeutic interventions in Alzheimer's disease[J]．RSC Adv，2018，8(42)：23780-23804．
[2]	ZENDEHBAD AS，NOROOZIAN M，SHAKIBA A，et al．Validation of iranian smell identification test for screening of mild cognitive impairment and Alzheimer's disease[J/OL]．Appl Neuropsychol Adult[2020-09-20]．https://www.tandfonline.com/doi/abs/10.1080/23279095.2019.1710508?journalCode=hapn21.
[3]	王莉，王虎，黄翰宇，等. 阿尔茨海默病发病机制的研究进展[J]. 中国老年学杂志， 2017， 37(19): 4953-4954.
[4]	HUSNA IBRAHIM N，YAHAYA MF，MOHAMED W，et al．Pharmacotherapy of Alzheimer's disease：seeking clarity in a time of uncertainty[J]．Front Pharmacol，2020，11：261．
[5]	牛阳，张霞，王荣，等. 八珍益智颗粒提取工艺研究[J]. 西北药学杂志， 2012， 27(4): 294-296.
[6]	冉玉兵，刘磊，张瑞芬，等．龙眼果肉提取物改善SAMP8小鼠学习记忆功能[J]．现代食品科技，2017，33(6)：1-8．
[7]	钟灵，王振富．山药多糖对老年性痴呆小鼠抗氧化能力的影响[J]．中国应用生理学杂志，2015，31(1)：42-43，48．
[8]	郭曼萍，赵俊男，施伟丽，等. 益智仁改善认知障碍的研究进展[J]. 中西医结合心脑血管病杂志， 2019， 17(18): 2778-2783.
[9]	SHI WT，ZHONG J，ZHANG Q，et al．Structural characterization and antineuroinflammatory activity of a novel heteropolysaccharide obtained from the fruits of Alpinia oxyphylla[J]．Carbohydr Polym，2020，229：115405．
[10]	徐煜彬，徐志立，李明玉，等.茯苓及其化学拆分组分学习记忆及镇静催眠的性味药理学研究[J].中草药，2014，45(11)：1577-1584.
[11]	LIU CX，LIU R，FAN HR，et al．Network pharmacology bridges traditional application and modern development of traditional Chinese medicine[J]．Chin Herb Med，2015，7(1)：3-17.
[12]	宗阳，丁美林，贾可可，等.基于网络药理学和分子对接法探寻达原饮治疗新型冠状病毒肺炎(COVID-19)活性化合物的研究[J].中草药，2020，51(4)：836-844.
[13]	ZAPLATIC E，BULE M，SHAH SZA，et al．Molecular mechanisms underlying protective role of quercetin in attenuating Alzheimer's disease[J]．Life Sci，2019，224：109-119．
[14]	文琪.益智提取物活性多成分在大鼠体内药代动力学研究[D].海口：海南医学院，2018.
[15]	马俊俏．益智仁挥发油对学习记忆障碍小鼠的改善作用及机制研究[D]．武汉：湖北中医药大学，2019．
[16]	马俊俏，吴勇，周俊璇，等.益智仁挥发油对东莨菪碱致小鼠学习记忆障碍的改善作用研究[J].中国药房，2018，29(22)：3074-3078.
[17]	冯星，王正濂，林永成，等.双白术内酯对Aβ_1-40致痴呆模型大鼠的作用[J].中国药理学通报，2009，25(7)：949-951.
[18]	CHOI GN，KIM JH，KWAK JH，et al．Effect of quercetin on learning and memory performance in ICR mice under neurotoxic trimethyltin exposure[J]．Food Chem，2012，132(2)：1019-1024．
[19]	KARIMIPOUR M，RAHBARGHAZI R，TAYEFI H，et al．Quercetin promotes learning and memory performance concomitantly with neural stem/progenitor cell proliferation and neurogenesis in the adult rat dentate gyrus[J]．Int J Dev Neurosci，2019，74：18-26．
[20]	QI Y，GUO L，JIANG YB，et al．Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles[J]．Drug Deliv，2020，27(1)：745-755．
[21]	李伟瀚，程笑，杨滢霖，等．山柰酚通过抑制神经炎症及保护血脑屏障而改善大鼠脑缺血再灌注神经功能[J]．中国药理学与毒理学杂志，2019，33(9)：673．
[22]	KHAJEVAND-KHAZAEI MR，ZIAEE P，MOTEVVALIZADEH SA，et al.Naringenin ameliorates learning and memory impairment following systemic lipopolysaccharide challenge in the rat[J].Eur J Pharmacol，2018，826：114-122.
[23]	王琳，金桂芳，余河汉，等.p38MAPK信号通路抗阿尔茨海默病的研究进展[J].医学综述，2019，25(24)：4834-4839.
[24]	汲广全．白术有效成分对巨噬细胞和树突状细胞免疫活性的研究[D]．广州：华南理工大学，2014．