基于网络药理学及分子对接方法研究黄芪治疗血管性痴呆的机制

熊瑞; 赵曼; 张浩; 吴天碧; 来小丹

doi:10.16016/j.2097-0927.202209162

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基于网络药理学及分子对接方法研究黄芪治疗血管性痴呆的机制

药学 | 更新时间：2026-01-09

- 基于网络药理学及分子对接方法研究黄芪治疗血管性痴呆的机制
- Mechanism of Astragalus membranaceus in treatment for vascular dementia based on network pharmacology and molecular docking
- 陆军军医大学学报 2023年45卷第10期页码：1070-1079
- 作者机构：
  
  400020 重庆, 中国人民解放军陆军第九五八医院药剂科
- 作者简介：
  
  [来小丹，E-mail：laixiaodan0926@sina.comLAI Xiaodan, E-mail: laixiaodan0926@sina.com
- 基金信息：
  
  重庆市科卫联合中医药项目(2022MSXM187);陆军军医大学科技创新能力提升专项项目(2022XQN28)
- DOI：10.16016/j.2097-0927.202209162
  中图分类号： R282.71;R319;R749.16
- 收稿：2022-09-19，
  
  修回：2023-01-10，
  
  纸质出版：2023-05-30
- 稿件说明：
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熊瑞, 赵曼, 张浩, 等. 基于网络药理学及分子对接方法研究黄芪治疗血管性痴呆的机制[J]. 陆军军医大学学报, 2023,45(10):1070-1079.

Rui XIONG, Man ZHAO, Hao ZHANG, et al. Mechanism of Astragalus membranaceus in treatment for vascular dementia based on network pharmacology and molecular docking[J]. Journal of Army Medical University, 2023, 45(10): 1070-1079.
熊瑞, 赵曼, 张浩, 等. 基于网络药理学及分子对接方法研究黄芪治疗血管性痴呆的机制[J]. 陆军军医大学学报, 2023,45(10):1070-1079. DOI： 10.16016/j.2097-0927.202209162.

Rui XIONG, Man ZHAO, Hao ZHANG, et al. Mechanism of Astragalus membranaceus in treatment for vascular dementia based on network pharmacology and molecular docking[J]. Journal of Army Medical University, 2023, 45(10): 1070-1079. DOI： 10.16016/j.2097-0927.202209162.

摘要

目的

利用网络药理学和分子对接方法研究黄芪治疗血管性痴呆(vascular dementia，VD)的机制。

方法

利用TCMSP数据库搜集黄芪活性成分，根据各成分的SMILES式在TargetNet数据库预测各成分的靶点；在GeneCards数据库搜集VD靶点，求黄芪活性成分靶点与VD靶点的交集，得到黄芪治疗VD的潜在靶点，利用Cytoscape 3.9.1软件构建活性成分-靶点网络；将黄芪治疗VD的潜在靶点导入STRING数据库构建蛋白-蛋白交互作用(protein-protein interaction，PPI)网络，并分析获得核心靶点；将核心靶点导入DAVID数据库进行基因本体(Gene Ontology，GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析；利用AutoDock软件对黄芪主要活性成分与VD核心靶点进行分子对接。

结果

共搜集到黄芪活性成分20个，包括华良姜素、异桔梗素、异黄酮烷、山奈酚和槲皮素等，得到预测靶点102个。收集并筛选得到VD靶点3 556个，得到黄芪与VD共同靶点71个，经PPI分析获得36个核心靶点，包括SLC6A4、ESR1、PTGS2、ABCB1、AR等。36个核心靶点富集到187个GO条目和32条KEGG通路，主要集中于神经功能、激素信号和血管生成方面。分子对接显示黄芪主要活性成分与VD核心靶点具有良好亲和力。

结论

黄芪可能主要通过调节神经功能、激素水平和血管生成治疗VD。

Abstract

Objective

To investigate the mechanism of

Astragalus membranaceus

(AM) in the treatment of vascular dementia (VD) by network pharmacology and molecular docking.

Methods

The active components of AM

were collected from TCMSP database

and the targets of active components were predicted in TargetNet database according to the SMILES. The VD targets were collected by GeneCards database

and the common targets of active components and VD was calculated to obtain the potential targets of AM in the treatment of VD. The active components-target network was constructed by Cytoscape 3.9.1 software. The potential targets of AM in the treatment of VD were imported into STRING database to construct protein-protein interaction (PPI) network

which was analyzed to obtain core targets. The core targets were imported into DAVID database to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The molecular docking was performed to assess the affinity of main active components of AM and the corresponding VD core targets

via

AutoDock software.

Results

A total of 20 active components of AM were collected

including jaranol

isorhamnetin

isoflavanone

kaempferol and quercetin

and a total of 102 predicted targets were obtained. A total of 3 556 VD targets were screened

71 common targets of AM and VD were calculated

and 36 core targets were obtained by PPI analysis

including SLC6A4

ESR1

PTGS2

ABCB1 and AR. A total of 187 GO items and 32 KEGG pathways were enriched

mainly focusing on neurological function

hormone signal and angiogenesis. Molecular docking showed good affinity between the main active components of AM and VD core targets.

Conclusion

AM treats VD mainly by regulating neurological function

hormone signal and angiogenesis.

关键词

Keywords

references

MOON W, HAN J W, BAE J B, et al . Disease burdens of Alzheimer's disease, vascular dementia, and mild cognitive impairment[J ] . J Am Med Dir Assoc, 2021, 22(10): 2093-2099. e3. DOI: 10.1016/j.jamda.2021.05.040.

张喜武, 刘安然, 窦金金. 基于中西医结合的血管性痴呆发病机制及治疗的研究进展[J/OL ] . 中国实验方剂学杂志, 1-15[2023-01-10 ] . DOI: 10.13422/j.cnki.syfjx.20221707 http://dx.doi.org/10.13422/j.cnki.syfjx.20221707 .

ZHANG X W, LIU A R, DOU J J. Research progress on pathogenesis and treatment of vascular dementia based on integrated traditional Chinese and Western medicine[J/OL ] . Chin J Exp Tradit Med Formulae, 1-15[2023-01-10 ] . DOI: 10.13422/j.cnki.syfjx.20221707 http://dx.doi.org/10.13422/j.cnki.syfjx.20221707 .

YANG Q, LIU J, HUANG K L, et al . A systematic revie w of the efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia[J ] . Medicine (Baltimore), 2022, 101(31): e29307. DOI: 10.1097/MD.0000000000029307.

中国医师协会神经内科分会认知障碍专业委员会, 《中国血管性认知障碍诊治指南》编写组. 2019年中国血管性认知障碍诊治指南[J]. 中华医学杂志, 2019, 99(35): 2737-2744. DOI: 10.3760/cma.j.issn.0376-2491.2019.35.005.

Cognitive Disorders Professional Committee of Neurology Branch of Chinese Medical Doctor Association, Compilation Group of Chinese Guidelines for Diagnosis and Treatment of Vascular Cognitive Disorders. Guidelines for diagnosis and treatment of vascular cognitive impairment in China in 2019[J ] . Natl Med J China, 2019, 99(35): 2737-2744. DOI: 10.3760/cma.j.issn.0376-2491.2019.35.005.

王飞雪, 黄小波, 裴卉, 等. 血管性痴呆中医病机理论的传承和发扬[J]. 世界中医药, 2022, 17(2): 221-224, 228. DOI: 10.3969/j.issn.1673-7202.2022.02.013.

WANG F X, HUANG X B, PEI H, et al . Inheritance and development of pathogenesis theory of vascular dementia in traditional Chinese medicine[J ] . World Chin Med, 2022, 17(2): 221-224, 228. DOI: 10.3969/j.issn.1673-7202.2022.02.013.

陈静, 陈炜, 伍媛, 等. 中药有效成分多靶点调控治疗血管性痴呆的研究进展[J]. 广西医学, 2019, 41(18): 2363-2365. DOI: 10.11675/j.issn.0253-4304.2019.18.20.

CHEN J, CHEN W, WU Y, et al . Research progress of multi-target regulation of effective compone nts of traditional Chinese medicine in the treatment of vascular dementia[J ] . Guangxi Med J, 2019, 41(18): 2363-2365. DOI: 10.11675/j.issn.0253-4304.2019.18.20.

周娇娇, 张青萍, 吴成挺, 等. 中医药调控相关信号通路治疗血管性痴呆的研究概述[J]. 中医药学报, 2022, 50(6): 116-120. DOI: 10.19664/j.cnki.1002-2392.220144.

ZHOU J J, ZHANG Q P, WU C T, et al . Overview of research on regulating related signal pathways of traditional Chinese medicine in treating vascular dementia[J ] . Acta Chin Med Pharmacol, 2022, 50(6): 116-120. DOI: 10.19664/j.cnki.1002-2392.220144.

马艳春, 胡建辉, 吴文轩, 等. 黄芪化学成分及药理作用研究进展[J]. 中医药学报, 2022, 50(4): 92-95. DOI: 10.19664/j.cnki.1002-2392.220092.

MA Y C, HU J H, WU W X, et al . Research progress on chemical constituents and pharmacological effects of Radix astragali[J ] . Acta Chin Med Pharmacol, 2022, 50(4): 92-95. DOI: 10.19664/j.cnki.1002-2392.220092.

张文涛, 崔应麟. 黄芪桂枝五物汤加减辅治老年血管性痴呆疗效观察[J]. 实用中医药杂志, 2022, 38(2): 242-244.

ZHANG W T, CUI Y L. Observation on the therapeutic effect of Huangqi Guizhi Wuwu Decoction on senile vascular-dementia[J]. J Pract Tradit Chin Med, 2022, 38(2): 242-244.

孙明竹. 加味益气聪明汤治疗血管性痴呆的临床研究[D]. 济南: 山东中医药大学, 2020.

SUN M Z. Clinical research on the treatment of vascular dementia with modified Yiqicongming decoction[D]. Jinan: Shandong University of Traditional Chinese Medicine, 2020.

黄晓丹. 益肺宣肺降浊方联合多奈哌齐治疗痰浊阻窍型血管性痴呆的临床研究[D]. 南宁: 广西中医药大学, 2019.

HUANG X D. The clinical study of Yifei Xuanfei Jiangzhu recipe combined with donepezil in the treatment of turbid and obstructive vascular dementia[D]. Nanning: Guangxi University of Chinese Medicine, 2019.

CHEN C C, LEE H C, CHANG J H, et al . Chinese herb Astragalus membranaceus enhances recovery of hemorrhagic stroke: double-blind, placebo-controlled, randomized study[J ] . Evid Based Complement Alternat Med, 2012, 2012: 708452. DOI: 10.1155/2012/708452..

赵亚鑫, 董婉婷. 黄芪多糖对血管性痴呆大鼠空间记忆和海马NMDAR1表达的影响[J]. 中华中医药学刊, 2016, 34(11): 2722-2724. DOI: 10.13193/j.issn.1673-7717.2016.11.046.

ZHAO Y X, DONG W T. Effect of Astragalus polysaccharide on spatial memory and hippocampal NMDAR1 expression in rats with vascular dementia[J ] . Chin Arch Tradit Chin Med, 2016, 34(11): 2722-2724. DOI: 10.13193/j.issn.1673-7717.2016.11.046.

陈攻, 江增宏. 黄芪总黄酮对血管性痴呆模型大鼠学习记忆损伤的干预作用[J]. 包头医学院学报, 2022, 38(7): 18-23. DOI: 10.16833/j.cnki.jbmc.2022.07.005.

CHEN G, JIANG Z H. Effect of total flavonoids of Astragalus on learning and memory impairment in vascular dementia rats[J ] . J Baotou Med Coll, 2022, 38(7): 18-23. DOI: 10.16833/j.cnki.jbmc.2022.07.005.

张娟利, 刘清, 王菲. 黄芪总皂苷改善血管性痴呆大鼠的认知功能[J]. 神经损伤与功能重建, 2022, 17(5): 281-284. DOI: 10.16780/j.cnki.sjssgncj.20201291.

ZHANG J L, LIU Q, WANG F. Astragaloside improves cognitive function of vascular dementia rats[J]. Neural Inj Funct Reconstr, 2022, 17(5): 281-284. DOI: 10.16780/j.cnki.sjssgncj.20201291.

DA SILVA J F, BOLSONI J A, DA COSTA R M, et al . Aryl hydrocarbon receptor (AhR) activation contributes to high-fat diet-induced vascular dysfunction[J ] . Br J Pharmacol, 2022, 179(12): 2938-2952. DOI: 10.1111/bph.15789.

REN R, LU Q, SHERCHAN P, et al . Inhibition of aryl hydrocarbon receptor attenuates hyperglycemia-induced hematoma expansion in an intracerebral hemorrhage mouse model[J ] . J Am Heart Assoc, 2021, 10(20): e022701. DOI: 10.1161/JAHA.121.022701.

KANDIAH N, PAI M C, SENANARONG V, et al . Rivastigmine: the advantages o f dual inhibition of acetylcholinesterase and butyryl cholinesterase and its role in subcortical vascular dementia and Parkinson's disease dementia[J ] . Clin Interv Aging, 2017, 12: 697-707. DOI: 10.2147/CIA.S129145.

BHATIA P, SINGH N. Tadalafil ameliorates memory deficits, oxidative stress, endothelial dysfunction and neuropathological changes in rat model of hyperhomo-cysteinemia induced vascular dementia[J]. Int J Neurosci, 2022, 132(4): 384-396. DOI: 10.1080/00207454.2020.1817009.

王峥, 林琳. 补阳还五汤联合西药治疗缺血性脑卒中后血管性痴呆疗效及对血清炎症因子、氧化应激指标和血管内皮活性物质的影响[J]. 现代中西医结合杂志, 2022, 31(4): 469-473, 490.

WANG Z, LIN L. Efficacy of Buyang Huanwu decoction combined with western medicine in the treatment of vascular dementia after ischemic stroke and its effect on serum inflammatory factors, oxidative stress indexes and vascular endothelial active substances[J]. Mod J Integr Tradit Chin West Med, 2022, 31(4): 469-473, 490.

王尊钙, 温小芬. 醒脑汤治疗血管性痴呆临床观察[J]. 中国中医急症, 2011, 20(1): 47-49. DOI: 10.3969/j.issn.1004-745X.2011.01.023.

WANG Z G, WEN X F. Clinical observation of Xingnao Decoction in treating vascular dementia[J]. J Emerg Tradit Chin Med, 2011, 20(1): 47-49. DOI: 10.3969/j.issn.1004-745X.2011.01.023.

LIU P, ZHAO H P, LUO Y M. Astragalus membranaceus anti-aging implications of (Huangqi): a well-known Chinese tonic[J ] . Aging Dis, 2017, 8(6), 868-886. DOI: 10.14336/AD.2017.0816.

LIU MM, SHAN G Z, JIANG H L, et al . Identification of miRNA and their regulatory effects induced by total flavonoids from dracocephalum moldavica in the treatment of vascular dementia[J ] . Front Pharmacol, 2021, 12: 796628. DOI: 10.3389/fphar.2021.796628.

WEN R, LV H N, JIANG Y, et al . Anti-inflammatory isoflavones and isoflavanones from the roots of Pongamia pinnata (L. )Pierre[J ] . Bioorg Med Chem Lett, 2018, 28(6): 1050-1055. DOI: 10.1016/j.bmcl.2018.02.026.

LIU T L, ZHANG Y, LIU J, et al . Evaluation of the acute and sub-acute oral toxicity of jaranol in Kunming mice[J ] . Front Pharmacol, 2022, 13: 903232. DOI: 10.3389/fphar.2022.903232.

TAN Z H, YANG G, QIU J, et al . Quercetin alleviates demyelination through regulating microglial phenotype transformation to mitigate neuropsychiatric symptoms in mice with vascular dementia[J ] . Mol Neurobiol, 2022, 59(5): 3140-3158. DOI: 10.1007/s12035-021-02712-3.

YAO Y, HAN D D, ZHANG T, et al . Quercetin improves cognitive deficits in rats with chronic cerebral ischemia and inhibits voltage-dependent sodium channels in hippocampal CA1 pyramidal neurons[J ] . Phytother Res, 2010, 24(1): 136-140. DOI: 10.1002/ptr.2902.

JAMALI-RAEUFY N, BALUCHNEJADMOJARAD T, ROGHANI M, et al . Isorhamnetin exerts neuroprotective effects in STZ-induced diabetic rats via attenuation of oxidative stress, inflammation andapoptosis[J ] . J Chem Neuroanat, 2019, 102: 101709. DOI: 10.1016/j.jchemneu.2019.101709..

WU Y Q, FAN L, WANG Y, et al . Isorhamnetin alleviates high glucose-aggravated inflammatory response and apoptosis in oxygen-glucose deprivation and reoxygenation-induced HT22 hippocampal neurons through Akt/SIRT1/Nrf2/HO-1 signaling pathway[J ] . Inflammation, 2021, 44(5): 1993-2005. DOI: 10.1007/s10753-021-01476-1.

HU W H, WANG H Y, XIA Y T, et al . Kaempferol, a major flavonoid in Ginkgo folium, potentiates angiogenic functions in cultured endothelial cells by binding to vascular endothelial growth factor[J ] . Front Pharmacol, 2020, 11: 526. DOI: 10.3389/fphar.2020.00526.

LI W H, CHENG X, YANG Y L, et al . Kaempferol attenuates neuroinflammation and blood brain barrier dysfunction to improve neurological deficits in cerebral ischemia/reperfusion rats[J ] . Brain Res, 2019, 1722: 146361. DOI: 10.1016/j.brainres.2019.146361.

RETTBERG J R, YAO J, DIAZ BRINTON R. Estrogen: a master regulator of bioenergetic systems in the brain and body[J]. Front Neuroendocrinol, 2014, 35(1): 8-30. DOI: 10.1016/j.yfrne.2013.08.001.

NGUYEN D H, SUMIEN N. Estrogen receptor involvement in vascular cognitive impairment and vascular dementia pathogenesis and treatment[J]. GeroScience, 2021, 43(1): 159-166. DOI: 10.1007/s11357-020-00263-4.

ABI-GHANEM C, ROBISON L S, ZULOAGA K L. Androgens' effects on cerebrovascular function in health and disease[J]. Biol Sex Differ, 2020, 11(1): 35. DOI: 10.1186/s13293-020-00309-4.

SERIPA D, MATERA M G, D'ONOFRIO G, et al . Polymorphism C in the serotonin transporter gene in depression-free elderly patients with vascular dementia[J ] . Dement Geriatr Cogn Disord, 2010, 29(5): 424-431. DOI: 10.1159/000275670.

LIN Y M, DAVAMANI F, YANG W C, et al . Association analysis of monoamine oxidase a gene and b ipolar affective disorder in Han Chinese[J ] . Behav Brain Funct, 2008, 4: 21. DOI: 10.1186/1744-9081-4-21.

ZHOU Z Y, LU C J, MENG S H, et al . Silencing of PTGS2 exerts promoting effects on angiogenesis endothelial progenitor cells in mice with ischemic stroke via repression of the NF-κB signaling pathway[J ] . J Cell Physiol, 2019, 234(12): 23448-23460. DOI: 10.1002/jcp.28914..

PAN Y S, CHEN W Q, WANG Y L, et al . Association between ABCB1 polymorphisms and outcomes of clopidogrel treatment in patients with minor stroke or transient ischemic attack: secondary analysis of a randomized clinical trial[J ] . JAMA Neurol, 2019, 76(5): 552-560. DOI: 10.1001/jamaneurol.2018.4775.

XU L Y, WANG Y. Combined influence of ABCB1 genetic polymorphism and DNA methylation on aspirin resistance in Chinese ischemic stroke patients[J]. Acta Neurol Belg, 2022, 122(4): 1057-1064. DOI: 10.1007/s13760-021-01714-1.

ZHANG LL, FAN Y Z, KONG X Y, et al . Neuroprotective effect of different physical exercises on cognition and behavior function by dopamine and 5-HT level in rats of vascular dementia[J ] . Behav Brain Res, 2020, 388: 112648. DOI: 10.1016/j.bbr.2020.112648.

LIN WW, WANG Y X, CHEN Y S, et al . Role of calcium signaling pathway-related gene regulatory networks in ischemic stroke based on multiple WGCNA and single-cell analysis[J ] . Oxid Med Cell Longev, 2021, 2021: 8060477. DOI: 10.1155/2021/8060477.

SZOEKE C, DOWNIE S J, PARKER A F, et al . Sex hormones, vascular factors and cognition[J ] . Front Neuroendocrinol, 2021, 62: 100927. DOI: 10.1016/j.yfrne.2021.100927.

XING Y, QIN W, LI F, et al . Associations between sex hormones and cognitive and neuropsychiatric manifestations in vascular dementia (VaD)[J ] . Arch Gerontol Geriatr, 2013, 56(1): 85-90. DOI: 10.1016/j.archger.2012.10.003.

KAUNDAL M, ZAMEER S, NAJMI A K, et al . Betulinic acid, a natural PDE inhibitor restores hippocampal cAMP/cGMP and BDNF, improve cerebral blood flow and recover memory deficits in permanent BCCAO induced vascular dementia in rats[J ] . Eur J Pharmacol, 2018, 832: 56-66. DOI: 10.1016/j.ejphar.2018.05.015.

YU WW, JIN H Q, SUN W, et al . Connexin43 promotes angiogenesis through activating the HIF-1α/VEGF signaling pathway under chronic cerebral hypoperfusion[J ] . J Cereb Blood Flow Metab, 2021, 41(10): 2656-2675. DO I: 10.1177/0271678X211010354.

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