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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 3
Mar.  2021
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Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(3): 582-589

Mechanism of Xiaozheng Huoluo prescription in preventing liver fibrosis in rats via the ERK5 pathway: An analysis based on network pharmacology

DOI: 10.3969/j.issn.1001-5256.2021.03.016
  • 1.

    Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China

  • 2.

    Department of Rheumatism, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, China

  • Received Date: 2020-09-09
  • Accepted Date: 2020-10-29
  • Published Date: 2021-03-20
    Abstract
  •   Objective  To investigate the mechanism of Xiaozheng Huoluo prescription (XZHLF) in the prevention and treatment of liver fibrosis based on network pharmacology.  Methods  TCMSP database, Chemistry Database, ETCM database, chemical source network database, ChemSrc database, and PubChem database were searched and a literature review was performed to collect the chemical components of each traditional Chinese medicine of XZHLF, Swiss ADME database was used to screen out the active components of each traditional Chinese medicine of XZHLF, and Swiss Target Prediction database was used to predict the targets of these active components; GeneCards and OMIN databases were used to collect the disease targets of liver fibrosis, and Venn diagrams were used to obtain the potential targets of XZHLF in the prevention and treatment of liver fibrosis. Cytoscape 3.7.1 software was used to establish a "drug-active component" network for XZHLF and an "active component-potential target" network for XZHLF in the prevention and treatment of liver fibrosis. Metascape database was used to perform GO and KEGG enrichment analysis of potential targets, and bubble charts were plotted for the top 20 pathways with the highest number of enriched genes. The MAPK signaling pathway among the top 20 KEGG pathways was analyzed to plot an "active component-potential target-pathway" network. Healthy Sprague-Dawley rats were randomly divided into blank control group (K group), model group (M group), colchicine-positive control group (Y group), high-dose XZHLF group (G group), middle-dose XZHLF group (Z Group), and low-dose XZHLF group (D group), and a rat model of liver fibrosis was established by CCl4; the drug was administered simultaneously for 8 weeks. Western blot was used to measure the protein expression of ERK5, p-ERK5, MEK5, and MEKK3 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups.  Results  A total of 110 active components were screened out from XZHLF and they acted on 923 targets, which were mapped to 6823 disease targets of liver fibrosis to obtain 647 potential targets. XZHLF might act on multiple protein targets such as EGFR, AKT1, IKBKB, MAPK8, and PDGFRB through the pathways including the MAPK signaling pathway and the biological processes including the regulation of MAPK cascade, thereby playing a role in the prevention and treatment of liver fibrosis. The M group had significant increases in the protein levels of ERK5, p-ERK5, MEK5, and MEKK3 in liver tissue compared with the K, Y, G, Z, and D groups (all P < 0.05), and the K group had significant reductions in the protein levels of ERK5, p-ERK5, MEK5, and MEKK3 in liver tissue compared with the Y, G, Z, and D groups (all P < 0.05).  Conclusion  Based on the method of network pharmacology, it is predicted that XZHLF may prevent and treat liver fibrosis via the MAPK signaling pathway, and it is verified through experiments that XZHLF prevents and treats liver fibrosis via the ERK5 pathway in the MAPK signaling pathway family. The high-dose XZHLF group shows the most obvious anti-liver fibrosis effect.

     

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    • References(20)
  • [1]
    WEISKIRCHEN R. Hepatoprotective and anti-fibrotic agents: It's time to take the next step[J]. Front Pharmacol, 2015, 6: 303. http://pubmedcentralcanada.ca/pmcc/articles/PMC4703795/
    [2]
    WYNN TA, RAMALINGAM TR. Mechanisms of fibrosis: Therapeutic translation for fibrotic disease[J]. Nat Med, 2012, 18(7): 1028-1040. DOI: 10.1038/nm.2807
    [3]
    SEKI E, BRENNER DA. Recent advancement of molecular mechanisms of liver fibrosis[J]. J Hepatobiliary Pancreat Sci, 2015, 22(7): 512-518. DOI: 10.1002/jhbp.245
    [4]
    TANG CF. Experimental and clinical study on Xiaozheng Huoluo Fang in prevention and treatment of liver arthralgia[D]. Changchun: Changchun University of Chinese Medicine, 2016. (in Chinese)

    唐成芳. 消癥活络方防治肝痹的实验与临床研究[D]. 长春: 长春中医药大学, 2016.
    [5]
    DAI DX, PAN Z, TANG CF, et al. Effect of Xiaozheng Huoluo Fang on the expression of α-SMA and TGF-β1 in liver tissue of rats with hepatic fibrosis[J]. Jilin J Chin Med, 2017, 37(2): 162-166. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZYJL201702016.htm

    代东雪, 潘志, 唐成芳, 等. 消癥活络方对肝纤维化大鼠肝组织α-SMA和TGF-β1表达的影响[J]. 吉林中医药, 2017, 37(2): 162-166. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYJL201702016.htm
    [6]
    LI S, ZHANG B. Traditional Chinese medicine network pharmacology: Theory, methodology and application[J]. Chin J Nat Med, 2013, 11(2): 110-120. http://europepmc.org/abstract/MED/23787177
    [7]
    JIN JJ, ZHONG M, YU SM, et al. Therapeutic effect of water extract of chuanposhi on hepatic fibrosis induced by carbon tetrachloride in rats[J]. Chin J Experi Tradi Med Form, 2012, 18(22): 258-262. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZSFX201222075.htm

    金俊杰, 钟鸣, 余胜民, 等. 穿破石水提取物对四氯化碳致大鼠肝纤维化的治疗作用[J]. 中国实验方剂学杂志, 2012, 18(22): 258-262. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSFX201222075.htm
    [8]
    XU SY, BIAN RL, CHEN X. Methodology of pharmacological experiment[M]. 3rd Ed. Beijing: People's Medical Publishing House, 2002: 1350-1351. (in Chinese)

    徐淑云, 卞如濂, 陈修. 药理实验方法学[M]. 第3版. 北京: 人民卫生出版社, 2002: 1350-1351.
    [9]
    LI ZY, TIAN YZ. Tibetan medicine Langqing atta treats liver fibrosis from stasis and heat[J]. J Changchun Univ Tradit Chin Med, 2019, 35(6): 1223-1225. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-CZXX201906062.htm

    李忠意, 田耀洲. 藏药郎庆阿塔从瘀热论治肝纤维化[J]. 长春中医药大学学报, 2019, 35(6): 1223-1225. https://www.cnki.com.cn/Article/CJFDTOTAL-CZXX201906062.htm
    [10]
    YI L, YANG JS. Discussion on TCM pathogenesis of liver fibrosis[J]. J Tradit Chin Med, 2005, 46(11): 806-808. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ200511001.htm

    衣蕾, 杨俊生. 肝纤维化中医病机浅探[J]. 中医杂志, 2005, 46(11): 806-808. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ200511001.htm
    [11]
    HAN B. Treatment of liver fibrosis with traditional Chinese Medicine[J]. Nei Mongol J Tradit Chin Med, 2014, 33(19): 39-40. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-NZYY201419039.htm

    韩斌. 浅谈肝纤维化的中医治疗[J]. 内蒙古中医药, 2014, 33(19): 39-40. https://www.cnki.com.cn/Article/CJFDTOTAL-NZYY201419039.htm
    [12]
    NISHIMOTO S, NISHIDA E. MAPK signalling: ERK5 versus ERK1/2[J]. EMBO Rep, 2006, 7(8): 782-786. DOI: 10.1038/sj.embor.7400755
    [13]
    CHAO TH, HAYASHI M, TAPPING RI, et al. MEKK3 directly regulates MEK5 activity as part of the big mitogen-activated protein kinase 1 (BMK1) signaling pathway[J]. J Biol Chem, 1999, 274(51): 36035-36038. DOI: 10.1074/jbc.274.51.36035
    [14]
    SUN W, KESAVAN K, SCHAEFER BC, et al. MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway[J]. J Biol Chem, 2001, 276(7): 5093-5100. DOI: 10.1074/jbc.M003719200
    [15]
    ENGLISH JM, VANDERBILT CA, XU S, et al. Isolation of MEK5 and differential expression of alternatively spliced forms[J]. J Biol Chem, 1995, 270(48): 28897-28902. DOI: 10.1074/jbc.270.48.28897
    [16]
    FANG DJ, LIANG WG, SHEN Y. Recent progress of extracellular signal regulated kinase 5 signal transduction pathway[J]. Guangdong Med J, 2012, 33(1): 140-143. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-GAYX201201065.htm

    方德健, 梁伟国, 沈雁. 细胞外信号调节激酶5信号转导通道研究的最新进展[J]. 广东医学, 2012, 33(1): 140-143. https://www.cnki.com.cn/Article/CJFDTOTAL-GAYX201201065.htm
    [17]
    WANG Y, SU B, XIA Z. Brain-derived neurotrophic factor activates ERK5 in cortical neurons via a Rap1-MEKK2 signaling cascade[J]. J Biol Chem, 2006, 281(47): 35965-35974. DOI: 10.1074/jbc.M605503200
    [18]
    DORADO F, VELASCO S, ESPARÍS-OGANDO A, et al. The mitogen-activated protein kinase Erk5 mediates human mesangial cell activation[J]. Nephrol Dial Transplant, 2008, 23(11): 3403-3411. DOI: 10.1093/ndt/gfn333
    [19]
    RAMSAY AK, MCCRACKEN SR, SOOFI M, et al. ERK5 signalling in prostate cancer promotes an invasive phenotype[J]. Br J Cancer, 2011, 104(4): 664-672. DOI: 10.1038/sj.bjc.6606062
    [20]
    URUSHIHARA M, TAKAMATSU M, SHIMIZU M, et al. ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis[J]. Am J Physiol Renal Physiol, 2010, 298(1): F167-F176. DOI: 10.1152/ajprenal.00124.2009
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