Volume 39 Issue 11
Nov.  2023
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Article Navigation >  Journal of Nanjing University of traditional Chinese Medicine  > 2023  >  39(11): 1113-1121
FU Chuan-jun, TAO Jia-sheng, YANG Liang, LIAO Li-xiu, TAN Xin-xin, LI Zhong-zheng, LI Xian-hui. Network Pharmacology Analysis and Experimental Verification of Isoliquiritigenin for the Treatment of Diabetic Encephalopathy[J]. Journal of Nanjing University of traditional Chinese Medicine, 2023, 39(11): 1113-1121. doi: 10.14148/j.issn.1672-0482.2023.1113
Citation: FU Chuan-jun, TAO Jia-sheng, YANG Liang, LIAO Li-xiu, TAN Xin-xin, LI Zhong-zheng, LI Xian-hui. Network Pharmacology Analysis and Experimental Verification of Isoliquiritigenin for the Treatment of Diabetic Encephalopathy[J]. Journal of Nanjing University of traditional Chinese Medicine, 2023, 39(11): 1113-1121. doi: 10.14148/j.issn.1672-0482.2023.1113
shu

Network Pharmacology Analysis and Experimental Verification of Isoliquiritigenin for the Treatment of Diabetic Encephalopathy

doi: 10.14148/j.issn.1672-0482.2023.1113
  • 1.

    College of Biology and Environmental Sciences, Medical Research Center, Jishou University, Jishou 416000, China

  • 2.

    School of Medicine, Jishou University, Jishou 416000, China

  • 3.

    Institute of Pharmaceutical Sciences, Jishou University, Jishou 416000, China

  • Received Date: 2023-04-11
    Available Online: 2023-11-24
    Abstract
  •   OBJECTIVE  This study aims to elucidate the mechanism of action of Isoliquiritigenin (ILG) in the treatment of Diabetic Encephalopathy (DE) based on network pharmacological analysis and in-vitro experiments.  METHODS  The potential targets of ILG were predicted using the HERB database and SwissTargetPrediction database. DE-associated disease targets were obtained from GeneCards, OMIM, and PharmGkb, and the intersecting targets between ILG and DE were identified using the Venny software. A PPI network was constructed using the STRING database, and core targets were screened out using Cytoscape software. GO function and KEGG pathway enrichment analyses were undertaken using R 4.0.3, followed by validation via molecular docking techniques and in vitro experiments.  RESULTS  65 intersecting targets between ILG and DE were identified in this study. Topological analysis yielded eight core targets namely, EGFR, ESR1, PTGS2, PPARG, GSK3β, CDK2, PIK3R1, and F3. GO function and KEGG pathway enrichment analyses revealed that ILG antagonizes DE through several biological processes which impact numerous cellular components and molecular functions such as response to lipopolysaccharides, protein phosphorylation, protein kinase activity, and serine/threonine/tyrosine kinase activity. Pathways implicated included the PI3K-Akt signaling pathway, protein polysaccharide signaling pathway in cancer, and endocrine resistance pathway. The molecular docking results showed that all eight core targets had a good binding with ILG, especially with GSK3β, with a binding energy of -7.22 kcal·mol-1. In vitro experiments indicated that ILG could improve high glucose-induced cell damage and activate the PI3K/AKT/GSK3β signaling pathway.  CONCLUSION  ILG is likely to exert its effects on GSK3β to regulate the PI3K/AKT/GSK3β signaling pathway, thereby alleviating DE.

     

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  • [1]
    LIU Y, LI MC, ZHANG Z, et al. Role of microglia-neuron interactions in diabetic encephalopathy[J]. Aging Res Rev, 2018, 42: 28-39. doi: 10.1016/j.arr.2017.12.005
    [2]
    SCHEMMEL KE, PADIYARA RS, D'SOUZA JJ. Aldose reductase inhibitors in the treatment of diabetic peripheral neuropathy: A review[J]. J Diabetes Complications, 2010, 24(5): 354-360. doi: 10.1016/j.jdiacomp.2009.07.005
    [3]
    曹月盈, 赵欣, 蒲小平. 糖尿病脑病的发病机制和药物治疗新进展[J]. 中国新药杂志, 2019, 28(9): 1065-1069. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ201909006.htm

    CAO YY, ZHAO X, PU XP. The pathogenesis of diabetic encephalopathy and the new progress of its drug therapy[J]. Chin J N Drugs, 2019, 28(9): 1065-1069. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ201909006.htm
    [4]
    张桂仙, 袁娅金, 熊薇, 等. 中医药防治糖尿病认知功能障碍研究进展[J]. 中国实验方剂学杂志, 2019, 25(23): 215-221. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSFX201923032.htm

    ZHANG GX, YUAN YJ, XIONG W, et al. Research progress on prevention and treatment of cognitive dysfunction in diabetes mellitus with traditional Chinese medicine[J]. Chin J Exp Tradit Med Formulae, 2019, 25(23): 215-221. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSFX201923032.htm
    [5]
    李红典, 郭翔宇, 刘冰, 等. 糖尿病合并认知功能障碍中医药研究现状与进展[J]. 辽宁中医药大学学报, 2022, 24(10): 115-120. doi: 10.13194/j.issn.1673-842x.2022.10.023

    LI HD, GUO XY, LIU B, et al. Current status and progress of Chinese medicine research on diabetes mellitus combined with cognitive impairment[J]. J Liaoning Univ Tradit Chin Med, 2022, 24(10): 115-120. doi: 10.13194/j.issn.1673-842x.2022.10.023
    [6]
    李媛, 战丽彬, 周雯. 乳酸在糖尿病认知功能障碍的作用及中医药研究进展[J]. 中华中医药学刊, 2023, 42(3): 163-167. doi: 10.13193/j.issn.1673-7717.2023.03.035

    LI Y, ZHAN LB, ZHOU W. Role of lactic acid in cognitive dysfunction of diabetes and research progress of traditional Chinese medicine[J]. Chin Arch Tradit Chin Med, 2023, 42(3): 163-167. doi: 10.13193/j.issn.1673-7717.2023.03.035
    [7]
    张明发, 沈雅琴. 甘草及其有效成分的抗糖尿病药理作用的研究进展[J]. 抗感染药学, 2015, 12(1): 1-5. https://www.cnki.com.cn/Article/CJFDTOTAL-KGYY201503006.htm

    ZHANG MF, SHEN YQ. Research advances in pharmacologic effects of licorice and its active components in hypoglycemia[J]. Anti Infect Pharm, 2015, 12(1): 1-5. https://www.cnki.com.cn/Article/CJFDTOTAL-KGYY201503006.htm
    [8]
    ZHU XB, LIU JK, CHEN SJ, et al. Isoliquiritigenin attenuates lipopolysaccharide-induced cognitive impairment through antioxidant and anti-inflammatory activity[J]. BMC Neurosci, 2019, 20(1): 41. doi: 10.1186/s12868-019-0520-x
    [9]
    LEE HK, YANG EJ, KIM JY, et al. Inhibitory effects of Glycyrrhizae radix and its active component, isoliquiritigenin, on Aβ(25-35)-induced neurotoxicity in cultured rat cortical neurons[J]. Arch Pharm Res, 2012, 35(5): 897-904. doi: 10.1007/s12272-012-0515-y
    [10]
    YANG EJ, MIN JS, KU HY, et al. Isoliquiritigenin isolated from Glycyrrhiza uralensis protects neuronal cells against glutamate-induced mitochondrial dysfunction[J]. Biochem Biophys Res Commun, 2012, 421(4): 658-664. doi: 10.1016/j.bbrc.2012.04.053
    [11]
    JANG EY, CHOE ES, HWANG M, et al. Isoliquiritigenin suppresses cocaine-induced extracellular dopamine release in rat brain through GABA(B) receptor[J]. Eur J Pharmacol, 2008, 587(1/2/3): 124-128.
    [12]
    刘志华, 孙晓波. 网络药理学: 中医药现代化的新机遇[J]. 药学学报, 2012, 47(6): 696-703. https://www.cnki.com.cn/Article/CJFDTOTAL-YXXB201206003.htm

    LIU ZH, SUN XB. Network pharmacology: New opportunity for the modernization of traditional Chinese medicine[J]. Acta Pharm Sin, 2012, 47(6): 696-703. https://www.cnki.com.cn/Article/CJFDTOTAL-YXXB201206003.htm
    [13]
    李梢. 网络靶标: 中药方剂网络药理学研究的一个切入点[J]. 中国中药杂志, 2011, 36(15): 2017-2020. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZY202322001.htm

    LI S. Network target: A starting point for traditional Chinese medicine network pharmacology[J]. China J Chin Mater Med, 2011, 36(15): 2017-2020. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZY202322001.htm
    [14]
    KIM S, CHEN J, CHENG TJ, et al. PubChem in 2021: New data content and improved web interfaces[J]. Nucleic Acids Res, 2021, 49(D1): D1388-D1395. doi: 10.1093/nar/gkaa971
    [15]
    AMBERGER JS, BOCCHINI CA, SCHIETTECATTE F, et al. OMIM. org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders[J]. Nucleic Acids Res, 2015, 43(Database issue): D789-D798.
    [16]
    BARBARINO JM, WHIRL-CARRILLO M, ALTMAN RB, et al. PharmGKB: A worldwide resource for pharmacogenomic information[J]. Wiley Interdiscip Rev Syst Biol Med, 2018, 10(4): e1417. doi: 10.1002/wsbm.1417
    [17]
    VON MERING C, HUYNEN M, JAEGGI D, et al. STRING: A database of predicted functional associations between proteins[J]. Nucleic Acids Res, 2003, 31(1): 258-261. doi: 10.1093/nar/gkg034
    [18]
    SHANNON P, MARKIEL A, OZIER O, et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks[J]. Genome Res, 2003, 13(11): 2498-2504. doi: 10.1101/gr.1239303
    [19]
    EBERHARDT J, SANTOS-MARTINS D, TILLACK AF, et al. AutoDock vina 1.2.0: New docking methods, expanded force field, and python bindings[J]. J Chem Inf Model, 2021, 61(8): 3891-3898.
    [20]
    LI L, LU JJ, WANG WT, et al. Potential targets of Euodiae Fructus in treatment of insomnia based on network pharmacology[J]. China J Chin Mater Med, 2021, 46(12): 3016-3023.
    [21]
    VAN SLOTEN TT, SEDAGHAT S, CARNETHON MR, et al. Cerebral microvascular complications of type 2 diabetes: Stroke, cognitive dysfunction, and depression[J]. Lancet Diabetes Endocrinol, 2020, 8(4): 325-336.
    [22]
    CUKIERMAN T, GERSTEIN HC, WILLIAMSON JD. Cognitive decline and dementia in diabetes: Systematic overview of prospective observational studies[J]. Diabetologia, 2005, 48(12): 2460-2469.
    [23]
    宋紫临, 吴丽丽, 秦灵灵, 等. PI3K/AKT信号通路与糖尿病的研究进展[J]. 世界科学技术-中医药现代化, 2019, 21(6): 1264-1269. https://www.cnki.com.cn/Article/CJFDTOTAL-SJKX201906034.htm

    SONG ZL, WU LL, QIN LL, et al. Research progress of PI3K/AKT signaling pathway and diabetes mellitus[J]. Mod Tradit Chin Med Mater Med World Sci Technol, 2019, 21(6): 1264-1269. https://www.cnki.com.cn/Article/CJFDTOTAL-SJKX201906034.htm
    [24]
    刘彦彤, 王郁金, 苏衍进, 等. 基于PI3K/AKT信号通路探讨中医药干预糖尿病血管病变的研究进展[J]. 环球中医药, 2023, 16(1): 175-181. https://www.cnki.com.cn/Article/CJFDTOTAL-HQZY202301040.htm

    LIU YT, WANG YJ, SU YJ, et al. Research progress of TCM Intervention in diabetic angiopathy based on PI3K/AKT signaling pathway[J]. Glob Tradit Chin Med, 2023, 16(1): 175-181. https://www.cnki.com.cn/Article/CJFDTOTAL-HQZY202301040.htm
    [25]
    王靖博, 田国庆. 中药干预PI3K/Akt信号通路调节糖尿病认知功能障碍研究现状[J]. 北京中医药, 2016, 35(9): 823-827. https://www.cnki.com.cn/Article/CJFDTOTAL-BJZO201609004.htm

    WANG JB, TIAN GQ. Research status of traditional Chinese medicine intervening PI3K/Akt signaling pathway to regulate diabetic cognitive impairment[J]. Beijing J Tradit Chin Med, 2016, 35(9): 823-827. https://www.cnki.com.cn/Article/CJFDTOTAL-BJZO201609004.htm
    [26]
    DOBLE BW, WOODGETT JR. GSK-3: Tricks of the trade for a multi-tasking kinase[J]. J Cell Sci, 2003, 116(Pt 7): 1175-1186.
    [27]
    GOBRECHT P, ANDREADAKI A, DIEKMANN H, et al. Promotion of functional nerve regeneration by inhibition of microtubule detyrosination[J]. J Neurosci, 2016, 36(14): 3890-3902.
    [28]
    LEI G, XIA Y, JOHNSON KM. The role of Akt-GSK-3beta signaling and synaptic strength in phencyclidine-induced neurodegeneration[J]. Neuropsychopharmacology, 2008, 33(6): 1343-1353.
    [29]
    HE Q, YANG JZ, ZHANG GY, et al. Sanhuang Jiangtang Tablet protects type 2 diabetes osteoporosis via AKT-GSK3β-NFATc1 signaling pathway by integrating bioinformatics analysis and experimental validation[J]. J Ethnopharmacol, 2021, 273: 113946.
    [30]
    GE Q, CHEN L, TANG M, et al. Analysis of mulberry leaf components in the treatment of diabetes using network pharmacology[J]. Eur J Pharmacol, 2018, 833: 50-62.
    [31]
    JOLIVALT CG, HURFORD R, LEE CA, et al. Type 1 diabetes exaggerates features of Alzheimer's disease in APP transgenic mice[J]. Exp Neurol, 2010, 223(2): 422-431.
    [32]
    HONDA H, NAGAI Y, MATSUNAGA T, et al. Isoliquiritigenin is a potent inhibitor of NLRP3 inflammasome activation and diet-induced adipose tissue inflammation[J]. J Leukoc Biol, 2014, 96(6): 1087-1100.
    [33]
    PENG F, DU QH, PENG C, et al. A review: The pharmacology of isoliquiritigenin[J]. Phytother Res, 2015, 29(7): 969-977.
    [34]
    YERRA VG, KALVALA AK, KUMAR A. Isoliquiritigenin reduces oxidative damage and alleviates mitochondrial impairment by SIRT1 activation in experimental diabetic neuropathy[J]. J Nutr Biochem, 2017, 47: 41-52.
    [35]
    ZHANG M, WU YQ, XIE L, et al. Isoliquiritigenin protects against blood-brain barrier damage and inhibits the secretion of pro-inflammatory cytokines in mice after traumatic brain injury[J]. Int Immunopharmacol, 2018, 65: 64-75.
    [36]
    LEE H, SHIN W, KIM K, et al. NGL-3 in the regulation of brain development, Akt/GSK3β signaling, long-term depression, and locomotive and cognitive behaviors[J]. PLoS Biol, 2019, 17(6): e2005326.
    [37]
    LIN XH, CHEN HB, CHEN ML, et al. Bone marrow-derived mesenchymal stem cells improve post-ischemia neurological function in rats via the PI3K/AKT/GSK-3β/CRMP-2 pathway[J]. Mol Cell Biochem, 2021, 476(5): 2193-2201.
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