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Current Bioinformatics

Editor-in-Chief

ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

Research Article

The Underlying Mechanisms of Wujiayizhi Granule in Treating Alzheimer's Disease

Author(s): Liu Xiang, Yue Lin, Xianhai Li, Qiang Tang, Fanbo Meng and Wei Chen*

Volume 17, Issue 8, 2022

Published on: 01 August, 2022

Page: [735 - 743] Pages: 9

DOI: 10.2174/1574893617666220509190343

Price: $65

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Abstract

Background: Wujiayizhi granule (WJYZG) is a kind of traditional Chinese medicine, which is used for treating Alzheimer's disease (AD). Although the clinical effect of WJYZG for AD is obvious, its underlying mechanism is still obscure.

Objective: Explore the mechanism of WJYZG in the treatment of AD by using bioinformatics methods.

Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) and Encyclopedia Database of Chinese Medicine (ETCM) were used to search the ingredients and targets of WJYZG. DisGeNET, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Terapeutic Target Database (TTD) were used to retrieve the targets of AD. The Cytoscape3.6.1 software was used to construct the interaction network of herbs-ingredients-targets. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the treatment mechanism of WJYZG on AD. Molecular docking was used to validate the interactions between the ingredients and targets.

Results: One hundred and thirty-three ingredients were identified from WJYZG. According to the herbingredient- targets network, quercetin, kaempferol, luteolin, anhydroicaritin, and 8-prenyl-flavone were screened out as the key ingredients, which can interact with the core targets encompassing INS, IL6, TNF, IL1B, CASP3, PTGS2, VEGFA, and PPARG. The enrichment analysis indicates that the treatment of AD by WJYZG was through inhibiting inflammation and neurocyte apoptosis, regulating the calcium ion signaling pathway and adjusting INS levels.

Conclusion: The underlying mechanisms of WJYZG in the treatment of AD were theoretically illustrated. We hope these results will enlighten the researches on AD.

Keywords: Wujiayizhi granule, traditional Chinese medicine, Alzheimer's disease, network pharmacology, molecular docking, bioinformatics.

Graphical Abstract

[1]
Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M. Alzheimer’s disease: Pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine 2019; 14: 5541-54.
[http://dx.doi.org/10.2147/IJN.S200490] [PMID: 31410002]
[2]
2021 Alzheimer’s disease facts and figures. Alzheimers Dement 2021; 17(3): 327-406.
[http://dx.doi.org/10.1002/alz.12328] [PMID: 33756057]
[3]
Soria Lopez JA, González HM, Léger GC. Alzheimer’s disease. Handb Clin Neurol 2019; 167: 231-55.
[http://dx.doi.org/10.1016/B978-0-12-804766-8.00013-3] [PMID: 31753135]
[4]
Tan MS, Cheah PL, Chin AV, Looi LM, Chang SW. A review on omics-based biomarkers discovery for Alzheimer’s disease from the bioinformatics perspectives: Statistical approach vs machine learning approach. Comput Biol Med 2021; 139: 104947.
[http://dx.doi.org/10.1016/j.compbiomed.2021.104947] [PMID: 34678481]
[5]
Liang W, Zhang K, Cao P, Liu X, Yang J, Zaiane O. Rethinking modeling Alzheimer’s disease progression from a multi-task learning perspective with deep recurrent neural network. Comput Biol Med 2021; 138: 104935.
[http://dx.doi.org/10.1016/j.compbiomed.2021.104935] [PMID: 34656869]
[6]
Kamble S, Barale S, Dhanavade M, Sonawane K. Structural significance of Neprylysin from Streptococcus suis GZ1 in the degradation of Aβ peptides, a causative agent in Alzheimer’s disease. Comput Biol Med 2021; 136: 104691.
[http://dx.doi.org/10.1016/j.compbiomed.2021.104691] [PMID: 34343891]
[7]
Vaz M, Silvestre S. Alzheimer’s disease: Recent treatment strategies. Eur J Pharmacol 2020; 887: 173554.
[http://dx.doi.org/10.1016/j.ejphar.2020.173554] [PMID: 32941929]
[8]
Athar T, Al Balushi K, Khan SA. Recent advances on drug development and emerging therapeutic agents for Alzheimer’s disease. Mol Biol Rep 2021; 48(7): 5629-45.
[http://dx.doi.org/10.1007/s11033-021-06512-9] [PMID: 34181171]
[9]
Liu J, Wang S, Zhang Y, Fan HT, Lin HS. Traditional Chinese medicine and cancer: History, present situation, and development. Thorac Cancer 2015; 6(5): 561-9.
[http://dx.doi.org/10.1111/1759-7714.12270] [PMID: 26445604]
[10]
Zhang Q, Zhou J, Zhang B. Computational Traditional Chinese Medicine diagnosis: A literature survey. Comput Biol Med 2021; 133: 104358.
[http://dx.doi.org/10.1016/j.compbiomed.2021.104358] [PMID: 33831712]
[11]
Pei H, Ma L, Cao Y, et al. Traditional Chinese medicine for Alzheimer’s disease and other cognitive impairment: A review. Am J Chin Med 2020; 48(3): 487-511.
[http://dx.doi.org/10.1142/S0192415X20500251] [PMID: 32329645]
[12]
Huang Y, Guo B, Shi B, Gao Q, Zhou Q. Chinese herbal medicine Xueshuantong enhances cerebral blood flow and improves neural functions in Alzheimer’s disease mice. J Alzheimers Dis 2018; 63(3): 1089-107.
[http://dx.doi.org/10.3233/JAD-170763] [PMID: 29710701]
[13]
Chledzik S, Strawa J, Matuszek K, Nazaruk J. Pharmacological effects of scutellarin, an active component of genus scutellaria and erigeron: A systematic review. Am J Chin Med 2018; 46(2): 319-37.
[http://dx.doi.org/10.1142/S0192415X18500167] [PMID: 29433387]
[14]
Li S, Zhang B. Traditional Chinese medicine network pharmacology: Theory, methodology and application. Chin J Nat Med 2013; 11(2): 110-20.
[http://dx.doi.org/10.1016/S1875-5364(13)60037-0] [PMID: 23787177]
[15]
Li X, Xiang L, Lin Y, Tang Q, Meng F, Chen W. Computational analysis illustrates the mechanism of qingfei paidu decoction in blocking the transition of COVID-19 patients from mild to severe stage. Curr Gene Ther 2022; 22(3): 277-89.
[http://dx.doi.org/10.2174/1566523221666210907162005] [PMID: 34493195]
[16]
Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017; 7: 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[17]
Xu HY, Zhang YQ, Liu ZM, et al. ETCM: An encyclopaedia of traditional Chinese medicine. Nucleic Acids Res 2019; 47(D1): D976-82.
[http://dx.doi.org/10.1093/nar/gky987] [PMID: 30365030]
[18]
Gfeller D, Grosdidier A, Wirth M, Daina A, Michielin O, Zoete V. SwissTargetPrediction: A web server for target prediction of bioactive small molecules Nucleic Acids Res 2014; 42(Web Server issue): W32-8.
[http://dx.doi.org/10.1093/nar/gku293]
[19]
Tang Y, Li M, Wang J, Pan Y, Wu FX. CytoNCA: A cytoscape plugin for centrality analysis and evaluation of protein interaction networks. Biosystems 2015; 127: 67-72.
[http://dx.doi.org/10.1016/j.biosystems.2014.11.005] [PMID: 25451770]
[20]
Yu G, Wang LG, Han Y, He QY. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS 2012; 16(5): 284-7.
[http://dx.doi.org/10.1089/omi.2011.0118] [PMID: 22455463]
[21]
Morris GM, Huey R, Olson AJ. Using autodock for ligand-receptor docking. Curr Protoc Bioinformatics 2008.
[http://dx.doi.org/10.1002/0471250953.bi0814s24]
[22]
Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010; 31(2): 455-61.
[PMID: 19499576]
[23]
Lei XQ, Chen A, Liu Y, He J. Research progress on pharmacological action of kaempferol. Studies Trace Elements Health 2017; 34(02): 61-2.
[24]
Xu GR, Chen ZG, Jiang YC, et al. Advances in pharmacokinetics and biological activity of quercetin. Zhongguo Nongxue Tongbao 2016; 32(13): 177-81.
[25]
Nabavi SF, Braidy N, Gortzi O, et al. Luteolin as an anti-inflammatory and neuroprotective agent: A brief review Brain Res Bull 2015; 119(Pt A): 1-11.
[http://dx.doi.org/10.1016/j.brainresbull.2015.09.002]
[26]
Wang HL, Liu XS, Shen T, Gu XY. Antioxidant effect of dehydrated icariin on aged rats. Zhongchengyao 2017; 39(8): 1698-700.
[27]
Arnold SE, Arvanitakis Z, Macauley-Rambach SL, et al. Brain insulin resistance in type 2 diabetes and Alzheimer disease: Concepts and conundrums. Nat Rev Neurol 2018; 14(3): 168-81.
[http://dx.doi.org/10.1038/nrneurol.2017.185] [PMID: 29377010]
[28]
Kaur S, Bansal Y, Kumar R, Bansal G. A panoramic review of IL-6: Structure, pathophysiological roles and inhibitors. Bioorg Med Chem 2020; 28(5): 115327.
[http://dx.doi.org/10.1016/j.bmc.2020.115327] [PMID: 31992476]
[29]
Kang MM, Wang R. The mechanism of inflammatory aging in the development of Alzheimer’s disease. Geriatrics Health Care 2020; 26(3): 504.
[30]
Chang R, Knox J, Chang J, et al. Blood-brain barrier penetrating biologic TNF-α inhibitor for Alzheimer’s disease. Mol Pharm 2017; 14(7): 2340-9.
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b00200] [PMID: 28514851]
[31]
Yang SS, Zhang B, Sun J. XU Y, Zhang C, Xia SM. Detection of interleukin and tumor necrosis factor in Patients with Alzheimer’s disease and its clinical significance. Journal of Qiqihar Medical College 2016; 37(26): 3294-5.
[32]
Lossi L, Castagna C, Merighi A. Caspase-3 mediated cell death in the normal development of the mammalian cerebellum. Int J Mol Sci 2018; 19(12): E3999.
[http://dx.doi.org/10.3390/ijms19123999] [PMID: 30545052]
[33]
Kondratskyi A, Kondratska K, Skryma R, Prevarskaya N. Ion channels in the regulation of apoptosis. Biochim Biophys Acta 2015; 1848 (10 Pt B): 2532-46.
[http://dx.doi.org/10.1016/j.bbamem.2014.10.030] [PMID: 25450339]
[34]
Chen Q, Liang B, Wang Z, et al. Influence of four polymorphisms in ABCA1 and PTGS2 genes on risk of Alzheimer’s disease: A meta-analysis. Neurol Sci 2016; 37(8): 1209-20.
[http://dx.doi.org/10.1007/s10072-016-2579-9] [PMID: 27215623]
[35]
Streit WJ, Khoshbouei H, Bechmann I. The role of microglia in sporadic Alzheimer’s disease. J Alzheimers Dis 2021; 79(3): 961-8.
[http://dx.doi.org/10.3233/JAD-201248] [PMID: 33361603]
[36]
Sánchez-Sarasúa S, Fernández-Pérez I, Espinosa-Fernández V, Sánchez-Pérez AM, Ledesma JC. Can we treat neuroinflammation in Alzheimer’s disease? Int J Mol Sci 2020; 21(22): E8751.
[http://dx.doi.org/10.3390/ijms21228751] [PMID: 33228179]
[37]
Chen WW, Zhang X, Huang WJ. Role of neuroinflammation in neurodegenerative diseases (Review). Mol Med Rep 2016; 13(4): 3391-6.
[http://dx.doi.org/10.3892/mmr.2016.4948] [PMID: 26935478]
[38]
Zaplatic E, Bule M, Shah SZA, Uddin MS, Niaz K. Molecular mechanisms underlying protective role of quercetin in attenuating Alzheimer’s disease. Life Sci 2019; 224: 109-19.
[http://dx.doi.org/10.1016/j.lfs.2019.03.055] [PMID: 30914316]
[39]
Khan H, Ullah H, Aschner M, Cheang WS, Akkol EK. Neuroprotective effects of quercetin in Alzheimer’s disease. Biomolecules 2019; 10(1): E59.
[http://dx.doi.org/10.3390/biom10010059] [PMID: 31905923]
[40]
Silva Dos Santos J, Gonçalves Cirino JP, de Oliveira Carvalho P, Ortega MM. The pharmacological action of kaempferol in central nervous system diseases: A review. Front Pharmacol 2021; 11: 565700.
[http://dx.doi.org/10.3389/fphar.2020.565700] [PMID: 33519431]
[41]
Beg T, Jyoti S, Naz F, et al. Protective effect of kaempferol on the transgenic drosophila model of Alzheimer’s disease. CNS Neurol Disord Drug Targets 2018; 17(6): 421-9.
[http://dx.doi.org/10.2174/1871527317666180508123050] [PMID: 29745345]
[42]
Galla L, Redolfi N, Pozzan T, Pizzo P, Greotti E. Intracellular calcium dysregulation by the Alzheimer’s disease-linked protein presenilin 2. Int J Mol Sci 2020; 21(3): E770.
[http://dx.doi.org/10.3390/ijms21030770] [PMID: 31991578]
[43]
Popugaeva E, Pchitskaya E, Bezprozvanny I. Dysregulation of intracellular calcium signaling in Alzheimer’s disease. Antioxid Redox Signal 2018; 29(12): 1176-88.
[http://dx.doi.org/10.1089/ars.2018.7506] [PMID: 29890840]
[44]
Mustaly-Kalimi S, Littlefield AM, Stutzmann GE. Calcium signaling deficits in glia and autophagic pathways contributing to neurodegenerative disease. Antioxid Redox Signal 2018; 29(12): 1158-75.
[http://dx.doi.org/10.1089/ars.2017.7266] [PMID: 29634342]
[45]
Cascella R, Cecchi C. Calcium dyshomeostasis in Alzheimer’s disease pathogenesis. Int J Mol Sci 2021; 22(9): 4914.
[http://dx.doi.org/10.3390/ijms22094914] [PMID: 34066371]
[46]
Zhang YM, Zhao JQ, Li XQ, et al. The effect of intracerebral insulin on Alzheimer’s Disease. Chin J Diabetes 2019; 27(06): 473-6.
[47]
Qin Y. The pathogenesis of type 2 diabetes and Alzheimer’s disease. Chinses Community Doctors 2020; 36(29): 58-9.

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