Ingredient Analysis

Based on UPLC-LTQ-Orbitrap-MS and network pharmacology methods to explore the potential mechanism of Liuwei Dihuang pills in the treatment of AD*

Expand
  • 1. Jiamusi University, Jiamusi 154007, China;
    2. Jiamusi College, Heilongjiang University of Traditional Chinese Medicine, Jiamusi 154007, China;
    3. Wuxi Affiliated Hospital, Nanjing University of Traditional Chinese Medicine, Wuxi 214071, China

Revised date: 2022-03-07

  Online published: 2024-06-26

Abstract

Objective: To identify the chemical components of Liuwei Dihuang pills into the blood and brain, and to explore the potential mechanism of Liuwei Dihuang pills in the treatment of Alzheimer’s disease(AD) by means of network pharmacology. Methods: Using ultra performance liquid chromatography-linear quadrupole ion trap-orbitrap high resolution mass spectrometry (UPLC-LTQ-Orbitrap-MS) technology,the components into the blood and brain was identified. Using TCMSP, Swiss Target Prediction, OMIM, GeneCards, TTD, DisGeNET and DrugBank database, composition and disease targets was predicted. Using String database and Cytoscape software, core targets were screened and a "component-target-disease-pathway" interaction network was constructed. Using Metascape database, Kyoto encyclopedia of genes and genome (KEGG) analysis and gene ontology(GO) were performed. Results: There were 21 components into blood and brain of Liuwei Dihuang pills, involving 169 AD-related target proteins. KEGG enriched a total of 175 metabolic pathways, which mainly involved neural active ligand-receptor interaction signaling pathways, AGE-RAGE signaling pathways in diabetic complications, and Alzheimer’s disease signaling pathways. GO functional enrichment analysis mainly involved processes such as synapses, cell responses to nitrogen compounds, and G protein coupled receptor activity. Conclusion: Liuwei Dihuang pills have the characteristics of multiple targets and multiple pathways in the treatment of AD. It may interfere with processes such as abnormal neuroactive ligand-receptor and insulin damage in the body, and provide a reference for further experimental verification of its mechanism of action.

Cite this article

WANG Di . Based on UPLC-LTQ-Orbitrap-MS and network pharmacology methods to explore the potential mechanism of Liuwei Dihuang pills in the treatment of AD*[J]. Chinese Journal of Pharmaceutical Analysis, 2022 , 42(4) : 580 -589 . DOI: 10.16155/j.0254-1793.2022.04.04

References

[1] 梁小娜, 林娟, 李新, 等. 复方丹参片及其拆方对血管性痴呆模型大鼠学习记忆能力的改善作用和机制探讨[J].中草药, 2019, 50(12):2884
LIANG XN, LIN J, LI X, et al. Effect and mechanism of compound Danshen tablet and its disassembled formula on learning and memory ability of vascular dementia model rats[J].Chin Tradit Herb Drugs, 2019, 50(12): 2884
[2] CHIOUA M, SERRANO E, DGACHI Y, et al. Synthesis, biological assessment and molecular modeling of racemic quino pyrano tacrines for Alzheimer’s disease therapy[J].Chem Select, 2018, 3(2):461
[3] ERBAYRAKTAR Z, EVLICE A, YENER G, et al. Effects of donepezil on liver and kidney functions for the treatment of Alzheimer’s disease[J].J Integr Neurosci, 2018, 16(3):335
[4] 周玲, 王长江, 黄敏, 等. 六味地黄丸加三七水提液对秀丽线虫抗氧化、缓解Aβ毒性及健康寿命的影响[J].中华中医药杂志, 2017, 32(5):1903
ZHOU L, WANG CJ, HUANG M, et al. Effects of Liuwei Dihuang pill plus Panax notoginseng aqueous extract on anti-oxidation and anti-Aβ toxicity of C. elegans[J].China J Tradit Chin Med Pharm, 2017, 32(5):1903
[5] 陈纪烨, 张永健, 周国锋, 等. 基于网络药理学的五苓散治疗慢性心力衰竭的机制研究[J].中草药, 2020, 51(20):5220
CHEN JY, ZHANG YJ, ZHOU GF, et al. Mechanism of Wuling powder in treatment of chronic heart failure based on network pharmacology[J].Chin Tradit Herb Drugs, 2020, 51(20):5220
[6] SEN N, HARA MR, KORNBERG MD, et al. Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis[J].Nat Cell Biol, 2008, 10(7):866
[7] LIU SY, ZHAO HD, WANG JL, et al. Association between polymorphisms of the AKT1 gene promoter and risk of the Alzheimer’s disease in a Chinese Han population with Type 2 diabetes[J].CNS Neurosci Ther, 2015, 21(8):619
[8] EZRA A, RABINOVICH NIKITIN I, RABINOVICH TOIDMAN P, et al. Multifunctional effect of human serum albumin reduces Alzheimer’s disease related pathologies in the 3xTg mouse model[J].J Alzheimers Dis, 2016, 50(1):175
[9] LIU J, LU F, GONG Y, et al. High expression of synthesis of cytochrome c oxidase 2 and TP53-induced glycolysis and apoptosis regulator can predict poor prognosis in human lung adenocarcinoma[J].Hum Pathol, 2018, 77:54
[10] PROFT J, WEISS N. A protective mutation against Alzheimer disease?[J].Commun Integr Biol, 2012, 5(4):301
[11] 刘小阳, 韩玉娇, 宋超, 等. 与阿尔兹海默症相关的G蛋白偶联受体研究进展[J].现代生物医学进展, 2012, 12(27):5380
LIU XY,HAN YJ, SONG C, et al. Advancement of G protein-coupled receptors related to Alzheimer’s disease[J].Prog Mod Biomed, 2012, 12(27):5380
[12] 宋皓, 李玉萍, 王松华, 等. 阿尔茨海默症突触功能障碍研究进展[J].生命科学, 2018, 30(1):20
SONG H, LI YP, WANG SH, et al. Research progress of synaptic dysfunction in Alzheimer’s disease[J].Chin Bull Life Sci, 2018, 30(1):20
[13] 张玉莲, 宋宛珊, 孙伟明, 等. 齐墩果酸唤醒阿尔兹海默病大鼠海马沉默突触作用及机制研究[J].中华中医药杂志, 2016, 31(9):3471
ZHANG YL, SONG WS, SUI WM, et al. Research on effects and mechanisms of oleanolic acid on waking silent synapses in Alzheimer’s disease rat hippocampus[J].China J Tradit Chin Med Pharm, 2016, 31(9):3471
[14] 杨翠翠, 包训杰, 张丽, 等. 山茱萸环烯醚萜苷对APP/PS1/Tau三转基因小鼠脑内病理变化的影响[J].首都医科大学学报, 2019, 40(4):588
YANG CC, BAO XJ, ZHANG L, et al. Effects of cornel iridoid glycoside on Alzheimer’s disease-associated neuropathology in APP/PS1/Tau transgenic mice[J].J Cap Med Univ, 2019, 40(4):588
[15] 李泽运, 冯甜甜, 兰月娇, 等. 基于超高效液相色谱-四极杆-飞行时间质谱和网络药理学技术分析银花感冒颗粒化学成分及其治疗作用的分子机制[J].中国医药, 2020, 15(7):1116
LI ZY, FENG TT, LAN YJ, et al. Observation of chemical constituents and molecular mechanism of Yinhuaganmao granules based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and network pharmacology[J].Chin Med, 2020, 15(7):1116
[16] 周军, 周丽, 曾庆仁, 等. 丹皮酚对AD模型鼠脑组织神经细胞与胶质细胞活性的影响[J].中成药, 2020, 20(1):12
ZHOU J, ZHOU L, ZENG QR, et al. The effect of paeonol on the activity of nerve cells and glial cells in the brain tissue of AD model rats[J].Chin Tradit Pat Med, 2020, 20(1):12
[17] CHUGH D, NILSSON P, AFJEI SA, et al. Brain inflammation induces post-synaptic changes during early synapse formation in adult-born hippocampal neurons[J].Exp Neurol, 2013, 250:176
[18] ROY ER, WANG B, WAN YW, et al. Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease[J].J Clin Invest, 2020, 130(4):1912
[19] 黄晓江, 蒋雯雯, 贾丛林, 等. 电针对血管性痴呆模型大鼠学习记忆功能及海马神经细胞凋亡和突触素表达的影响[J].中国老年学杂志, 2015, 17(35):4786
HUANG XJ, JIANG WW, JIA CL, et al. Effect of electroacupuncture on learning and memory function, hippocampal nerve cell apoptosis and synaptophysin expression in rats with vascular dementia[J].Chin J Gerontol, 2015, 17(35):4786
[20] 潘玲珍, 闫智勇, 左长英, 等. 长期使用地西泮对神经活性配体受体相互作用信号通路的影响[J].中国药科大学学报, 2011, 42(5):443
PAN LZ, YAN ZY, ZUO CY, et al. Influence of long-term usage of diazepam on neuroactive ligand-receptor interaction signaling pathway[J].J China Pharm Univ, 2011, 42(5):443
[21] LIU Y, LIU Z, WEI M, et al. Pharmacodynamic and urinary metabolomics studies on the mechanism of Schisandra polysaccharide in the treatment of Alzheimer’s disease[J].Food Funct, 2019, 10(1):432
[22] LIU Y, GAO Y, LI KX, et al. Pharmacokinetics and acetylcholine releasing effects of ginsenoside Rg1 in Hippocampus of beta-amyloid model rats[J].J Asian Nat Prod Res, 2019, 21(8):772
[23] YU YC, LI J, ZHANG M, et al. Resveratrol improves brain-gut axis by regulation of 5-HT-dependent signaling in the rat model of irritable bowel syndrome[J].Front Cell Neurosci, 2019, 13:1
[24] HASHEMI FIROUZI N, KOMAKI A, SOLEIMANI ASL S, et al. The effects of the 5-HT7 receptor on hippocampal long-term potentiation and apoptosis in a rat model of Alzheimer’s disease[J].Brain Res Bull, 2017, 135:85
[25] LI W, RISACHER SL, GAO S, et al. Type 2 diabetes mellitus and cerebrospinal fluid Alzheimer’s disease biomarker amyloid beta1-42 in Alzheimer’s disease neuroimaging initiative participants[J].Alzheimers Dement(Amst), 2018, 10:94
[26] GRIFFITH CM, EID T, ROSE GM, et al. Evidence for altered insulin receptor signaling in Alzheimer’s disease[J].Neuropharmacology, 2018, 136(Pt B):202
[27] LEE TW, KAO YH, CHEN YJ, et al. Therapeutic potential of vitamin D in AGE/RAGE-related cardiovascular diseases[J].Cell Mol Life Sci, 2019, 76(20):4103
Outlines

/