Volume 37 Issue 4
Jul.  2021
Turn off MathJax
Article Contents
WANG Xuan, XU Wei-chen, LUO Zi-chen, XU Yong, SHI Chen, XIE Tong, LIAO Ying-zhao, SHAN Jin-jun. UPLC/LTQ-Orbitrap-MS Combined with Network Pharmacology to Explore the Mechanism of Platycodon Grandiflorum in the Treatment of Nonalcoholic Fatty Liver Disease[J]. Journal of Nanjing University of traditional Chinese Medicine, 2021, 37(4): 554-562. doi: 10.14148/j.issn.1672-0482.2021.0554
Citation: WANG Xuan, XU Wei-chen, LUO Zi-chen, XU Yong, SHI Chen, XIE Tong, LIAO Ying-zhao, SHAN Jin-jun. UPLC/LTQ-Orbitrap-MS Combined with Network Pharmacology to Explore the Mechanism of Platycodon Grandiflorum in the Treatment of Nonalcoholic Fatty Liver Disease[J]. Journal of Nanjing University of traditional Chinese Medicine, 2021, 37(4): 554-562. doi: 10.14148/j.issn.1672-0482.2021.0554

UPLC/LTQ-Orbitrap-MS Combined with Network Pharmacology to Explore the Mechanism of Platycodon Grandiflorum in the Treatment of Nonalcoholic Fatty Liver Disease

doi: 10.14148/j.issn.1672-0482.2021.0554
  • Received Date: 2021-04-11
    Available Online: 2021-12-21
  • Publish Date: 2021-07-10
  • OBJECTIVE  Combining UPLC/LTQ-Orbitrap-MS technology with network pharmacology method to predict the target of Platycodon grandiflorum in the treatment of non-alcoholic fatty liver disease (NAFLD) and the potential mechanism, and carrying out relevant experimental verification, in order to reveal the effective substances and mechanism of Platycodon grandiflorum in the treatment of NAFLD.METHODS  The active components of Platycodon grandiflorum were screened by UPLC/LTQ-Orbitrap-MS and TCMSP database. Swiss Target Prediction Database was used to predict the active components of Platycodon grandiflorum. Targets of NAFLD were obtained through OMIM, Disgenet, TTD and other databases. The disease-related targets were mapped to the potential targets of compounds to obtain the common targets, and the information was imported into Cytoscape software and String online analysis platform to make network diagram and PPI diagram, respectively, and topological analysis was carried out at the same time. Functional enrichment analysis of key target genes GO and KEGG was carried out by using Bioconductor bioinformatics software package based on R software. NAFLD mouse model was established, the results of network pharmacology enrichment analysis were verified by pathological staining and qPCR.RESULTS  Combined with the results of mass spectrometry and database screening, a total of 13 active components, 278 drug targets, 1 536 disease targets and 83 common targets were screened in Platycodon, involving PI3K-AKT, insulin resistance, TNF-α, IL-17, JAK-STAT, T cell receptors and other signaling pathways. Experimental verification showed that the key target genes were differentially expressed.CONCLUSION  This study reveals the active components of Platycodon grandiflorum in the treatment of NAFLD and its mechanism of action, it provides reference value for further research.

     

  • loading
  • [1]
    BYRNE CD, TARGHER G. NAFLD: A multisystem disease[J]. J Hepatol, 2015, 62(S1): 47-64. http://www.ncbi.nlm.nih.gov/pubmed/25920090
    [2]
    FRIEDMAN SL, NEUSCHWANDER-TETRI BA, RINELLA M, et al. Mechanisms of NAFLD development and therapeutic strategies[J]. Nat Med, 2018, 24(7): 908-922. doi: 10.1038/s41591-018-0104-9
    [3]
    ZHOU F, ZHOU JH, WANG WX, et al. Unexpected rapid increase in the burden of NAFLD in China from 2008 to 2018: A systematic review and meta-analysis[J]. Hepatology, 2019, 70(4): 1119-1133. doi: 10.1002/hep.30702
    [4]
    MARENGO A, ROSSO C, BUGIANESI E. Liver cancer: Connections with obesity, fatty liver, and cirrhosis[J]. Annu Rev Med, 2016, 67: 103-117. doi: 10.1146/annurev-med-090514-013832
    [5]
    张声生, 李军祥. 非酒精性脂肪性肝病中医诊疗专家共识意见(2017)[J]. 中医杂志, 2017, 58(19): 1706-1710. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ201719022.htm
    [6]
    张志聪. 本草崇原[M]. 北京: 中国中医药出版社, 2019: 136.
    [7]
    尚志钧. 神农本草经辑注[M]. 尚元胜, 尚元耦, 邱浩, 整理. 北京: 学苑出版社, 2013: 86.
    [8]
    CHOI JH, JIN SW, CHOI CY, et al. Saponins from the roots of Platycodon grandiflorum ameliorate high fat diet-induced non-alcoholic steatohepatitis[J]. Biomed Pharmacother, 2017, 86: 205-212. doi: 10.1016/j.biopha.2016.11.107
    [9]
    庄延双, 蔡宝昌, 张自力. 网络药理学在中药研究中的应用进展[J]. 南京中医药大学学报, 2021, 37(1): 156-160. http://xb.njucm.edu.cn/jnutcmns/ch/reader/view_abstract.aspx?file_no=zr20210129&flag=1
    [10]
    DENG YL, REN HM, YE XW, et al. Integrated phytochemical analysis based on UPLC-Q-TOF-MS/MS, network pharmacology, and experiment verification to explore the potential mechanism of Platycodon grandiflorum for chronic bronchitis[J]. Front Pharmacol, 2020, 11: 564131. doi: 10.3389/fphar.2020.564131
    [11]
    LEE JW, JI SH, KIM GS, et al. Global profiling of various metabolites in Platycodon grandiflorum by UPLC-QTOF/MS[J]. Int J Mol Sci, 2015, 16(11): 26786-26796. doi: 10.3390/ijms161125993
    [12]
    SUK KT, KIM DJ. Gut microbiota: Novel therapeutic target for nonalcoholic fatty liver disease[J]. Exp Rev Gastroenterol Hepatol, 2019, 13(3): 193-204. doi: 10.1080/17474124.2019.1569513
    [13]
    YE Q, ZOU B, YEO YH, et al. Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: A systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol, 2020, 5(8): 739-752. doi: 10.1016/S2468-1253(20)30077-7
    [14]
    YOUNOSSI ZM, KOENIG AB, ABDELATIF D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes[J]. Hepatology, 2016, 64(1): 73-84. doi: 10.1002/hep.28431
    [15]
    ZHOU JH, ZHOU F, WANG WX, et al. Epidemiological features of NAFLD from 1999 to 2018 in China[J]. Hepatology, 2020, 71(5): 1851-1864. doi: 10.1002/hep.31150
    [16]
    ESTES C, ANSTEE QM, ARIAS-LOSTE MT, et al. Modeling nafld disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030[J]. J Hepatol, 2018, 69(4): 896-904. doi: 10.1016/j.jhep.2018.05.036
    [17]
    金在久. 桔梗的化学成分及药理和临床研究进展[J]. 时珍国医国药, 2007, 18(2): 506-509. doi: 10.3969/j.issn.1008-0805.2007.02.148
    [18]
    KIM TW, LIM JH, SONG IB, et al. Hepatoprotective and anti-hepatitis C viral activity of Platycodon grandiflorum extract on carbon tetrachloride-induced acute hepatic injury in mice[J]. J Nutr Sci Vitaminol, 2012, 58(3): 187-194. doi: 10.3177/jnsv.58.187
    [19]
    LEE KJ, KIM JY, JUNG KS, et al. Suppressive effects of Platycodon grandiflorum on the progress of carbon tetrachloride-induced hepatic fibrosis[J]. Arch Pharm Res, 2004, 27(12): 1238-1244. doi: 10.1007/BF02975888
    [20]
    LEE KJ, CHOI JH, KIM HG, et al. Protective effect of saponins derived from the roots of Platycodon grandiflorum against carbon tetrachloride induced hepatotoxicity in mice[J]. Food Chem Toxicol, 2008, 46(5): 1778-1785. doi: 10.1016/j.fct.2008.01.017
    [21]
    LEE KJ, YOU HJ, PARK SJ, et al. Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice[J]. Cancer Lett, 2001, 174(1): 73-81. doi: 10.1016/S0304-3835(01)00678-4
    [22]
    HWANG YP, CHOI JH, KIM HG, et al. Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells[J]. Toxicol Appl Pharmacol, 2013, 267(2): 174-183. doi: 10.1016/j.taap.2013.01.001
    [23]
    LEE WC, JUNG HA, CHOI JS, et al. Protective effects of luteolin against apoptotic liver damage induced by D-galactosamine/lipopolysaccharide in mice[J]. J Nat Prod, 2011, 74(9): 1916-1921. doi: 10.1021/np2003935
    [24]
    AL-MEGRIN WA, ALKHURIJI AF, YOUSEF AOS, et al. Antagonistic efficacy of luteolin against lead acetate exposure-associated with hepatotoxicity is mediated via antioxidant, anti-inflammatory, and anti-apoptotic activities[J]. Antioxidants, 2019, 9(1): 10. doi: 10.3390/antiox9010010
    [25]
    席梅, 邢建国, 王丽, 等. 金合欢素的降血脂及抗动脉粥样硬化作用及机制初探[J]. 药学学报, 2019, 54(5): 846-853. https://www.cnki.com.cn/Article/CJFDTOTAL-YXXB201905010.htm
    [26]
    马纳, 李亚静, 范吉平. 金合欢素药理研究进展[J]. 中国现代应用药学, 2018, 35(10): 1591-1595. https://www.cnki.com.cn/Article/CJFDTOTAL-XDYD201810035.htm
    [27]
    CHEN JJ, SUN X, XIA TT, et al. Pretreatment with dihydroquercetin, a dietary flavonoid, protected against concanavalin A-induced immunological hepatic injury in mice and TNF-α/ActD-induced apoptosis in HepG2 cells[J]. Food Funct, 2018, 9(4): 2341-2352. doi: 10.1039/C7FO01073G
    [28]
    ZHANG Y, JIN Q, LI X, et al. Amelioration of alcoholic liver steatosis by dihydroquercetin through the modulation of AMPK-dependent lipogenesis mediated by P2X7R-NLRP3-inflammasome activation[J]. J Agric Food Chem, 2018, 66(19): 4862-4871. doi: 10.1021/acs.jafc.8b00944
    [29]
    潮蓉, 武小娟, 王羽辉, 等. P2X7R/NLRP3信号通路在酒精性肝损伤中的作用[J]. 中国药理学通报, 2018, 34(4): 491-495. doi: 10.3969/j.issn.1001-1978.2018.04.011
    [30]
    COBBINA E, AKHLAGHI F. Non-alcoholic fatty liver disease (NAFLD) - pathogenesis, classification, and effect on drug metabolizing enzymes and transporters[J]. Drug Metab Rev, 2017, 49(2): 197-211. doi: 10.1080/03602532.2017.1293683
    [31]
    袁欣, 韩莉花, 张娜, 等. 异芒果苷对高脂饮食诱导大鼠肝脏损伤的改善作用[J]. 南京中医药大学学报, 2019, 35(4): 453-457. http://xb.njucm.edu.cn/jnutcmns/ch/reader/view_abstract.aspx?file_no=ZR20190423&flag=1
    [32]
    KHAN RS, BRIL F, CUSI K, et al. Modulation of insulin resistance in nonalcoholic fatty liver disease[J]. Hepatology, 2019, 70(2): 711-724. http://d.wanfangdata.com.cn/periodical/ed824efada5fefd4b382a370f6591cb1
    [33]
    许伟辰, 罗子宸, 谢彤, 等. 中药桔梗研究进展及其质量标志物预测初步分析[J]. 南京中医药大学学报, 2021, 37(2): 294-302. http://xb.njucm.edu.cn/jnutcmns/ch/reader/view_abstract.aspx?file_no=zr20210224&flag=1
    [34]
    迟毓婧, 李晶, 管又飞, 等. PI3K-Akt信号传导通路对糖代谢的调控作用[J]. 中国生物化学与分子生物学报, 2010, 26(10): 879-885. https://www.cnki.com.cn/Article/CJFDTOTAL-SWHZ201010002.htm
    [35]
    ZHANG Z, LIU H, LIU J. Akt activation: A potential strategy to ameliorate insulin resistance[J]. Diabetes Res Clin Pract, 2019, 156: 107092. doi: 10.1016/j.diabres.2017.10.004
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(9)  / Tables(3)

    Article Metrics

    Article views (416) PDF downloads(225) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return