基于网络药理学的核桃防治老年痴呆功能成分及其作用靶点研究

doi:10.14088/j.cnki.issn0439-8114.2021.24.034

湖北农业科学 ›› 2021, Vol. 60 ›› Issue (24): 151-159.doi: 10.14088/j.cnki.issn0439-8114.2021.24.034

基于网络药理学的核桃防治老年痴呆功能成分及其作用靶点研究

许成梅¹, 陈丹², 徐冬月¹, 赵庆宇婧³, 林玉萍¹, 赵声兰¹

1.云南中医药大学中药学院,昆明 650500;
2.云南省烟草质量监督检测站,昆明 650106;
3.昆明海关技术中心,昆明 650200

收稿日期:2021-01-04 出版日期:2021-12-25 发布日期:2022-01-04
通讯作者: 赵声兰（1962-）,女,云南个旧人,教授,主要从事药食资源研究与开发利用研究,（电话）13330431529（电子信箱）13330431529@163.com。
作者简介:许成梅（1995-）,女,云南楚雄人,在读硕士研究生,研究方向为中药资源开发与利用,（电话）18288680414（电子信箱） 3210911564@qq.com;
基金资助:
国家自然科学基金项目（81760735）; 云南省生物医药重大专项（2018ZF013）; 云南省科技厅-云南中医药大学联合专项重点项目（2019FF002-006）

Study on functional components and targets of walnut in prevention and treatment of Alzheimer's disease based on network pharmacology

XU Cheng-mei¹, CHEN Dan², XU Dong-yue¹, ZHAO-QING Yu-jing³, LIN Yu-ping¹, ZHAO Sheng-lan¹

1. School of Chinese Materia Medica,Yunnan University of Chinese Medicine,Kunming 650500,China;
2. Yunnan Tobacco Quality Supervision and Inspection Station,Kunming 650106,China;
3. Kunming Custom Technical Center,Kunming 650200,China

Received:2021-01-04 Online:2021-12-25 Published:2022-01-04

摘要/Abstract

摘要： 基于网络药理学方法探究核桃（Juglans regia L.）防治老年痴呆（Alzheimer's disease,AD）的作用机制,通过TCMSP数据库和文献挖掘获得核桃的活性成分及相应潜在靶点;使用OMIM等数据库进行AD相关基因预测和筛选;采用Cytoscape 3.7.2软件构建“药物-活性成分-疾病-靶点”网络以形成核桃防治AD的成分及靶点相互作用关系,并进行GO功能和KEGG通路富集分析。结果表明,筛选获得29种核桃活性成分,其中17种成分具有AD相关靶点159个,PTGS1/2、RXRA、RELA、MAOB和NOS3可能是AD的关键靶点,主要信号通路为AGE-RAGE信号通路、动脉粥样硬化、PI3K-Akt信号通路、IL-17信号通路和HIF-1信号通路。核桃通过多成分、多靶点、多途径防治AD,其中作用靶点最多的成分为槲皮素、油酸、鞣花酸;受最多化合物作用的靶点为前列腺素过氧化物合成酶、视黄酸受体、转录因子p65、单胺氧化酶和一氧化氮合酶。

关键词: 核桃（Juglans regia L.）, 老年痴呆, 网络药理学, 作用机制

Abstract: The mechanism of walnut（Juglans regia L.） in prevention and treatment of Alzheimer's disease（AD） was explored based on network pharmacology. The active components and potential targets of walnut were obtained by TCMSP database and literature mining. The prediction and screening of AD related genes were performed using databases such as OMIM; Cytoscape 3.7.2 software was used to construct a “drug-active component-disease-target” network to formation of the interactive relationship of walnuts toprevent AD components and target, and analysis of GO function and KEGG pathway enrichment. The results showed that 29 walnut active ingredients were screened, 17 of which had 159 AD-related targets. PTGS1/2, RXRA, RELA, MAOB and NOS3 may be the key targets of AD. The main signal pathways were AGE-RAGE signaling pathway, atherosclerosis, PI3K-Akt signaling pathway, IL-17 signaling pathway and HIF-1 signaling pathway. Walnut can prevent and control AD through multi-component, multi-target, and multi-pathway. The components with the most targets are quercetin, oleic acid, and ellagic acid; the targets affected by the most compounds are prostaglandin G/H synthase, retinoic acid receptor RXR-alpha, transcription factor p65, amine oxidase [flavin-containing] B and nitric oxide synthase.

Key words: walnut（Juglans regia L.）, Alzheimer's disease, internet pharmacology, mechanism of action

中图分类号:

S664.1

许成梅, 陈丹, 徐冬月, 赵庆宇婧, 林玉萍, 赵声兰. 基于网络药理学的核桃防治老年痴呆功能成分及其作用靶点研究[J]. 湖北农业科学, 2021, 60(24): 151-159.

XU Cheng-mei, CHEN Dan, XU Dong-yue, ZHAO-QING Yu-jing, LIN Yu-ping, ZHAO Sheng-lan. Study on functional components and targets of walnut in prevention and treatment of Alzheimer's disease based on network pharmacology[J]. HUBEI AGRICULTURAL SCIENCES, 2021, 60(24): 151-159.

参考文献

[1] 赵文姣, 孙德群. 以糖原合成酶激酶-3为靶标的抗老年痴呆新药研究进展[J] . 有机化学, 2018, 38(7): 1596-1607.
[2] 朱晓奕, 洪庆, 徐卫东, 等. 经典方玉屏风散防治老年痴呆症探讨[J] . 亚太传统医药, 2018(1): 74-76.
[3] 李时珍. 本草纲目[M] . 北京: 人民卫生出版社,1982.
[4] 中华人民共和国药典委员会. 中华人民共和国药典(一部)[M] . 北京: 中国医药科技出版社, 2015.
[5] LIU J, CHEN D, WANG Z, et al.Protective effect of walnut on d-galactose-induced aging mouse model[J] . Food science & nutrition, 2019,7: 969-976.
[6] 周丽莎, 朱书秀, 望庐山. 核桃仁提取物对老年痴呆模型大鼠Ach、ChAT及AchE活性的影响[J] . 中国医院药学杂志, 2011,31(6):446-449.
[7] 周丽莎, 朱书秀, 王小月. 核桃仁提取物对老年痴呆模型大鼠IL-1、IL-6含量影响的实验研究[J] . 江汉大学学报(自然科学版), 2012,40(1): 89-91.
[8] RU J, LI P, WANG J, et al.TCMSP: A database of systems pharmacology for drug discovery from herbal medicines[J] . Journal of cheminformatics, 2014, 6: 13.
[9] WANG J,HOU T.Advances in computationally modeling human oral bioavailability[J] . Advanced drug delivery reviews,2015,86: 11-16.
[10] HU Q, FENG M, LAI L, et al.Prediction of drug-likeness using deep autoencoder neural networks[J] . Front gene, 2018, 9: 585.
[11] HAANING N,DAMSGAARD E M,MOOS T.The blood-brain barrier in ageing persons[J] . Ugeskr laeger,2018,180:V08170576.
[12] WANG Y,ZHANG S,LI F,et al.Therapeutic target database 2020:Enriched resource for facilitating research and early development of targeted therapeutics[J] . Nucleic acids research,2020, 48(D1):1031-1041.
[13] 张晶,李冰冰,黄敏仪,等. 基于网络药理学的参芪降糖颗粒治疗2型糖尿病机制探讨[J] . 中草药,2020,51(19):4873-4883.
[14] ZINSMAIER K E.Cysteine-string protein's neuroprotective role[J] . Journal of neurogenetics,2010,24(3): 120-132.
[15] KIM S, DARCY I K. A topological analysis of difference topology experiments of condensin with topoisomerase II[J/OL] . Biology open, 2020,9(4): https:doi.org/10.110V795898.
[16] WONG K L, MURAKAMI K, ROUTTENBERG A.Dietary cis-fatty acids that increase protein F₁ phosphorylation enhance spatial memory[J] . Brain research, 1989, 505: 302-305.
[17] PIERMARTIRI T C, PAN H, CHEN J, et al.Alpha-Linolenic acid-induced increase in neurogenesis is a key factor in the improvement in the passive avoidance task after soman exposure[J] . Neuromolecular medicine, 2015, 17: 251-269.
[18] SALEHI A,RABIEI Z,SETORKI M.Effect of gallic acid on chronic restraint stress-induced anxiety and memory loss in male BALB/c mice[J] . Iranian journal of basic medical sciences,2018,21: 1232-1237.
[19] OGUT E, SEKERCI R, AKCAY G, et al.Protective effects of syringic acid on neurobehavioral deficits and hippocampal tissue damages induced by sub-chronic deltamethrin exposure[J] .Neurotoxicology and teratology, 2019, 76: 106839.
[20] MHILLAJ E, CATINO S, MICELI F M, et al.Ferulic acid improves cognitive skills through the activation of the heme oxygenase system in the rat[J] . Molecular neurobiology, 2018, 55: 905-916.
[21] SHAHMOHAMADY P, EIDI A, MORTAZAVI P, et al.Effect of sinapic acid on memory deficits and neuronal degeneration induced by intracerebroventricular administration of streptozotocin in rats[J] . Polish journal of pathology, 2018, 69: 266-277.
[22] ZHONG L, LIU H, ZHANG W, et al.Ellagic acid ameliorates learning and memory impairment in APP/PS1 transgenic mice via inhibition of β-amyloid production and tau hyperphosphorylation[J] . Experimental and therapeutic medicine,2018,16:4951-4958.
[23] RAMIS M R, SARUBBO F, TEJADA S, et al.Chronic polyphenon-60 or catechin treatments increase brain monoamines syntheses and hippocampal SIRT1 levels improving cognition in aged rats[J] . Nutrients, 2020, 12(2): 326.
[24] HERMAWATI E, ARFIAN N, MUSTOFA M, et al.Chlorogenic acid ameliorates memory loss and hippocampal cell death after transient global ischemia[J] . European journal of neuroscience, 2020, 51: 651-669.
[25] RAMALINGAYYA G V, CHERUKU S P, NAYAK P G, et al.Rutin protects against neuronal damage in vitro and ameliorates doxorubicin-induced memory deficits in vivo in Wistar rats[J] . Drug design development and therapy, 2017, 11: 1011-1026.
[26] KE F,LI H R,CHEN X X,et al.Quercetin alleviates LPS-induced depression-like behavior in rats via regulating BDNF-related imbalance of copine 6 and TREM1/2 in the hippocampus and PFC[J] . Frontiers in pharmacology, 2020, 10: 1544.
[27] YANG S,ZHANG J,YAN Y,et al.Network pharmacology-based strategy to investigate the pharmacologic mechanisms of atractylodes macrocephala koidz. for the treatment of chronic gastritis[J] . Frontiers in pharmacology,2019,10:1629.
[28] HE D, HUANG J H, ZHANG Z Y, et al.A network pharmacology-based strategy for predicting active ingredients and potential targets of LiuWei DiHuang Pill in treating type 2 diabetes mellitus[J] . Drug design development and therapy,2019, 13: 3989-4005.
[29] KÖLSCH H, LÜTJOHANN D, JESSEN F, et al. RXRA gene variations influence Alzheimer’s disease risk and cholesterol metabolism[J] . Journal of cellular and molecular medicine,2009,13(3): 589-598.
[30] JO S, YARISHKIN O, HWANG Y J, et al.GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease[J] . Nature medicine, 2014, 20: 886-896.
[31] LIU P, ZHAO B Y, WEI M, et al.Activation of inflammation is associated with amyloid-β accumulation induced by chronic sleep restriction in rats[J] . Journal of alzheimers disease, 2020,74(3): 759-773.
[32] 孟贺, 宫世强, 刘明妍. 基于网络药理学方法分析金津玉液汤治疗2型糖尿病的机制及其治疗阿尔茨海默病的潜在性[J] . 中国新药杂志,2019, 28(1): 26-33.
[33] LIU Y W, ZHU X, ZHANG L, et al.Cerebroprotective effects of ibuprofen on diabetic encephalopathy in rats[J] . Pharmacology biochemistry and behavior, 2014, 117: 128-136.
[34] CUI W, WANG S, WANG Z, et al.Inhibition of PTEN attenuates endoplasmic reticulum stress and apoptosis via activation of PI3K/AKT pathway in Alzheimer’s disease[J] . Neurochemical research, 2017, 42: 3052-3060.
[35] ZHANG X, ZHOU K, WANG R, et al.Hypoxia-inducible factor lα (HIF-1α)-mediated hypoxia increases BACE1 expression and β-amyloid generation[J] . Journal of biological chemistry, 2007, 282(15): 10873-10880.

基于网络药理学的核桃防治老年痴呆功能成分及其作用靶点研究

Study on functional components and targets of walnut in prevention and treatment of Alzheimer's disease based on network pharmacology

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	徐冬月, 赵声兰. 基于网络药理学及分子对接技术分析核桃治疗高尿酸血症的作用机制[J]. 湖北农业科学, 2023, 62(8): 120-126.
[2]	陈睿, 潘小芳, 杨楠, 霍丽妮, 陈姎玲, 梁天坚. 基于GC-MS和网络药理学探究茉莉花根挥发油镇静安神作用[J]. 湖北农业科学, 2023, 62(11): 84-91.
[3]	陈姎玲, 潘小芳, 徐浩, 陈睿, 霍丽妮, 梁燕. 基于网络药理学及分子对接探讨灵芝药理机制[J]. 湖北农业科学, 2023, 62(10): 83-90.
[4]	柯昌虎, 严慧, 赵阳, 朱军, 李志浩. 基于网络药理学和分子对接探讨黄精抗衰老的作用机制[J]. 湖北农业科学, 2023, 62(10): 100-108.
[5]	曾格格, 刘毅, 刘天琪, 黄振阳, 丁晨薇. 基于GC-MS和网络药理学探讨当归-肉桂药对的抗炎作用机制[J]. 湖北农业科学, 2022, 61(18): 113-119.
[6]	秦华珍, 钟贵, 陈俊其, 何瑞坤, 戴庆玲, 柳俊辉. 三味山姜属中药黄酮类成分对胃溃疡寒证大鼠的作用机制研究[J]. 湖北农业科学, 2022, 61(15): 153-156.
[7]	侯金豆. 文旅产业与乡村振兴有效耦合的逻辑与策略优化[J]. 湖北农业科学, 2022, 61(13): 252-256.
[8]	张彤, 赵芸, 黄伟, 崔宏春. 天然多糖抑菌活性及机理研究进展[J]. 湖北农业科学, 2022, 61(11): 158-162.
[9]	董雪静, 朱华, 王颖. 基于网络药理学和免疫浸润的大蒜素对肝细胞癌作用机制分析[J]. 湖北农业科学, 2022, 61(10): 83-89.
[10]	韦露玲, 张淼, 黄飘玲, 滕建北. 桂枝抗菌活性成分及其作用机制研究进展[J]. 湖北农业科学, 2021, 60(21): 21-25.
[11]	韩倩, 陈勇, 王竟静, 魏江存, 黄周艳, 陈良妮. 网络药理学方法研究三七治疗关节炎的作用机制[J]. 湖北农业科学, 2021, 60(2): 109-115.
[12]	吴昌鸿, 杨英. 黄芪提取物抗病毒作用的研究进展[J]. 湖北农业科学, 2021, 60(18): 5-8.
[13]	刘巧明, 谢胜, 奉建芳, 王力宁, 陈雅璐, 林国彪, 黄晓燕, 梁健钦. 健脾益气口服液对小鼠小肠推进功能的影响及其作用机制分析[J]. 湖北农业科学, 2021, 60(17): 98-103.
[14]	武佳琪, 黄金海. 糖基化在囊膜病毒感染中的作用机制[J]. 湖北农业科学, 2021, 60(15): 11-15.
[15]	王春花, 曲雪嘉, 孔令钰, 孙雪芳. 基于系统药理学菊花清热解毒功效的分子机制研究[J]. 湖北农业科学, 2021, 60(10): 137-141.