The mechanism of black mulberry reatment for AD was studied based on HPLC fingerprint and network pharmacology

  • CHEN Xuanshi ,
  • LIU Mengwen ,
  • SHEN Jing ,
  • Ayinuer·Baikere ,
  • HE Shiru ,
  • Tuerxunayi·Dawuti ,
  • XIAO Hui
Expand
  • (School of Public Health, Xinjiang Medical University, Urumqi 830011, China)

Received date: 2024-01-15

  Revised date: 2024-02-26

  Online published: 2024-08-02

Abstract

The fingerprint of black mulberry was characterized using high-performance liquid chromatography (HPLC) to analyze its primary active constituents.Additionally, the molecular mechanism underlying the treatment of Alzheimer's disease (AD) by black mulberry was investigated through the integration of network pharmacology and molecular docking technology.The fingerprints of 12 batches of black mulberry were established via HPLC, and common peaks were identified.The 12 batches of black mulberry samples were evaluated through similarity evaluation, cluster analysis, principal component analysis, OPLS-DA analysis, and TOPSIS analysis.The active ingredients and target information of black mulberry were obtained from the TCMSP database and the Swiss Target Prediction platform.Disease target information for AD was acquired from the Gene Cards database and AD database to identify potential targets for AD treatment.PPI network diagram was constructed, and topological analysis was performed using the String database and Cytoscape 3.7.2.The core targets were enriched by GO and KEGG using R software.Molecular docking simulations were conducted using Auto Dock software.The HPLC fingerprints of black mulberry samples exhibited a similarity exceeding 0.96, identifying three chromatographic peaks.Cluster analysis categorized the 12 batches of samples into three categories, with principal component analysis results consistent with those of cluster analysis.Twelve core targets were identified after network pharmacological screening, and 1 480 GO entries and 104 KEGG pathways were obtained through enrichment analysis of core targets.Black mulberry may regulate the PI3K-Akt signaling pathway, neutrophil exagination and other signaling pathways through core targets, thereby regulating inflammation and other responses, and achieving the effect of treating and preventing AD through multi-target-multi-pathway.

Cite this article

CHEN Xuanshi , LIU Mengwen , SHEN Jing , Ayinuer·Baikere , HE Shiru , Tuerxunayi·Dawuti , XIAO Hui . The mechanism of black mulberry reatment for AD was studied based on HPLC fingerprint and network pharmacology[J]. Food and Fermentation Industries, 2024 , 50(13) : 270 -278 . DOI: 10.13995/j.cnki.11-1802/ts.038603

References

[1] BADHWAR A, MCFALL G P, SAPKOTA S, et al.A multiomics approach to heterogeneity in Alzheimer's disease:Focused review and roadmap[J].Brain:a Journal of Neurology, 2020, 143(5):1315-1331.
[2] GUZMAN-MARTINEZ L, CALFÍO C, FARIAS G A, et al.New frontiers in the prevention, diagnosis, and treatment of Alzheimer's disease[J].Journal of Alzheimer's Disease:JAD, 2021, 82(s1):S51-S63.
[3] 钟雪, 李倩, 宋昱, 等.基于网络药理学的桑葚药理功能定位及作用机制分析[J].天津师范大学学报(自然科学版), 2022, 42(4):46-51;63.
ZHONG X, LI Q, SONG Y, et al.Analysis of pharmacological function and mechanism of action of mulberry based on network pharmacology[J].Journal of Tianjin Normal University (Natural Science Edition), 2022, 42(4):46-51;63.
[4] LIN Z W, GAN T T, HUANG Y Z, et al.Anti-inflammatory activity of mulberry leaf flavonoids in vitro and in vivo[J].International Journal of Molecular Sciences, 2022, 23(14):7694.
[5] MAQSOOD M, ANAM SAEED R, SAHAR A, et al.Mulberry plant as a source of functional food with therapeutic and nutritional applications:A review[J].Journal of Food Biochemistry, 2022, 46(11):e14263.
[6] PALACHAI N, WATTANATHORN J, MUCHIMAPURA S, et al.Phytosome loading the combined extract of mulberry fruit and ginger protects against cerebral ischemia in metabolic syndrome rats[J].Oxidative Medicine and Cellular Longevity, 2020, 2020:5305437.
[7] LIU D X, DU D Q.Mulberry fruit extract alleviates cognitive impairment by promoting the clearance of amyloid-β and inhibiting neuroinflammation in Alzheimer's disease mice[J].Neurochemical Research, 2020, 45(9):2009-2019.
[8] OCHIISHI T, KAKU M, KAJSONGKRAM T, et al.Mulberry fruit extract alleviates the intracellular amyloid-β oligomer-induced cognitive disturbance and oxidative stress in Alzheimer's disease model mice[J].Genes to Cells, 2021, 26(11):861-873.
[9] 王腾华, 罗颖懿, 王驭辰, 等.基于GC-MS与网络药理学的青皮挥发油防治阿尔茨海默症的活性成分及作用机制研究[J].中国药房, 2020, 31(17):2093-2100.
WANG T H, LUO Y Y, WANG Y C, et al.Study on active components and mechanism of volatile oil of citri reticulatae preventing and treating Alzheimer's disease based on GC-MS and network pharmacology[J].China Pharmacy, 2020, 31(17):2093-2100.
[10] 罗连响, 黄芳芳, 吴锐剑, 等.花青素对阿尔兹海默病关键药理途径的生物信息学分析及实验验证[J].中国免疫学杂志, 2021, 37(18):2217-2224.
LUO L X, HUANG F F, WU R J, et al.Bioinformatics analysis and experimental validation of cyanidin on key pharmacological pathways of Alzheimer's disease[J].Chinese Journal of Immunology, 2021, 37(18):2217-2224.
[11] ZHANG T T, WEI W, CHANG S R, et al.Integrated network pharmacology and comprehensive bioinformatics identifying the mechanisms and molecular targets of Yizhiqingxin formula for treatment of comorbidity with Alzheimer's disease and depression[J].Frontiers in Pharmacology, 2022, 13:853375.
[12] HUANG X Y, XUE L L, CHEN T B, et al.Miracle fruit seed as a potential supplement for the treatment of learning and memory disorders in Alzheimer's disease[J].Frontiers in Pharmacology, 2023, 13:1080753.
[13] MA X Y, ZHAO Y, YANG T, et al.Integration of network pharmacology and molecular docking to explore the molecular mechanism of Cordycepin in the treatment of Alzheimer's disease[J].Frontiers in Aging Neuroscience, 2022, 14:1058780.
[14] ZHANG J, LI H J, ZHANG Y B, et al.Uncovering the pharmacological mechanism of stemazole in the treatment of neurodegenerative diseases based on a network pharmacology approach[J].International Journal of Molecular Sciences, 2020, 21(2):427.
[15] MARTIZ R M, PATIL S M, ABDULAZIZ M, et al.Defining the role of isoeugenol from Ocimum tenuiflorum against diabetes mellitus-linked Alzheimer's disease through network pharmacology and computational methods[J].Molecules, 2022, 27(8):2398.
[16] LUO H Y, GUO H J, ZHOU Y, et al.Neutrophil extracellular traps in cerebral ischemia/reperfusion injury:Friend and foe[J].Current Neuropharmacology, 2023, 21(10):2079-2096.
[17] SMYTH L C D, MURRAY H C, HILL M, et al.Neutrophil-vascular interactions drive myeloperoxidase accumulation in the brain in Alzheimer's disease[J].Acta Neuropathologica Communications, 2022, 10(1):38.
[18] JANSSON D, DIERIKS V B, RUSTENHOVEN J, et al.Cardiac glycosides target barrier inflammation of the vasculature, meninges and choroid plexus[J].Communications Biology, 2021, 4(1):260.
[19] JOHNSON E C B, CARTER E K, DAMMER E B, et al.Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level[J].Nature Neuroscience, 2022, 25(2):213-225.
[20] CARL E.Proliferation and differentiation deficits are a major convergence point for neurodevelopmental disorders[J].Trends in Neurosciences, 2016, 39(5):290-299.
[21] ZU G X, SUN K Y, LI L, et al.Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus[J].Scientific Reports, 2021, 11(1):22959.
[22] WU L Y, XIAN X H, XU G Y, et al.Toll-like receptor 4:A promising therapeutic target for Alzheimer's disease[J].Mediators of Inflammation, 2022, 2022:7924199.
[23] YANG J L, WISE L, FUKUCHI K I.TLR4 cross-talk with NLRP3 inflammasome and complement signaling pathways in Alzheimer's disease[J].Frontiers in Immunology, 2020, 11:724.
[24] QIN Z J, GU M, ZHOU J, et al.Triggering receptor expressed on myeloid cells 2 activation downregulates toll-like receptor 4 expression and ameliorates cognitive impairment in the Aβ1-42-induced Alzheimer's disease mouse model[J].Synapse, 2020, 74(10):e22161.
[25] SHAH S, BROCK E J, JI K, et al.Ras and Rap1:A tale of two GTPases[J].Seminars in Cancer Biology, 2019, 54:29-39.
[26] KOSURU R, CHRZANOWSKA M.Integration of Rap1 and calcium signaling[J].International Journal of Molecular Sciences, 2020, 21(5):1616.
[27] XIA Y Y, QADOTA H, WANG Z H, et al.Neuronal C/EBPβ/AEP pathway shortens life span via selective GABAnergic neuronal degeneration by FOXO repression[J].Science Advances, 2022, 8(13):eabj8658.
[28] GOSWAMI S, KAREEM O, GOYAL R K, et al.Role of forkhead transcription factors of the O class (FoxO) in development and progression of Alzheimer's disease[J].CNS & Neurological Disorders Drug Targets, 2020, 19(9):709-721.
[29] SHARMA V K, SINGH T G, SINGH S, et al.Apoptotic pathways and Alzheimer's disease:Probing therapeutic potential[J].Neurochemical Research, 2021, 46(12):3103-3122.
[30] WU Y B, CHEN M Q, JIANG J L.Mitochondrial dysfunction in neurodegenerative diseases and drug targets via apoptotic signaling[J].Mitochondrion, 2019, 49:35-45.
[31] JAYARAMAN A, REYNOLDS R.Diverse pathways to neuronal necroptosis in Alzheimer's disease[J].The European Journal of Neuroscience, 2022, 56(9):5428-5441.
[32] LI X Q, CHENG Y X, QIN Y P, et al.Chrysophanol exerts neuroprotective effects via interfering with endoplasmic reticulum stress apoptotic pathways in cell and animal models of Alzheimer's disease[J].The Journal of Pharmacy and Pharmacology, 2022, 74(1):32-40.
[33] TAJBAKHSH A, READ M, BARRETO G E, et al.Apoptotic neurons and amyloid-beta clearance by phagocytosis in Alzheimer's disease:Pathological mechanisms and therapeutic outlooks[J].European Journal of Pharmacology, 2021, 895:173873.
Outlines

/

〈 〉