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中华肾病研究电子杂志

中华肾病研究电子杂志 ›› 2021, Vol. 10 ›› Issue (04) : 189 -197. doi: 10.3877/cma.j.issn.2095-3216.2021.04.002

论著

基于网络药理学和分子对接研究益肾健脾利水方治疗肾小球肾炎的作用机制
金美玲1, 李典耕2, 张伟光3, 尹智炜4,†(), 杨洪娟5,†()   
  1. 1. 100020　北京，首都医科大学附属北京朝阳医院肾内科
    2. 100020　北京，首都医科大学附属北京朝阳医院科研处
    3. 100853　北京，解放军总医院第一医学中心肾脏病医学部、解放军肾脏病研究所、肾脏疾病国家重点实验室、国家慢性肾病临床医学研究中心、肾脏疾病研究北京市重点实验室
    4. 100853　北京，解放军总医院第一医学中心肾脏病医学部、解放军肾脏病研究所、肾脏疾病国家重点实验室、国家慢性肾病临床医学研究中心、肾脏疾病研究北京市重点实验室；050017　石家庄，河北医科大学中西医结合学院
    5. 050031　石家庄，河北医科大学第一医院中西医结合肾内科
  • 收稿日期:2021-06-21 出版日期:2021-08-26
  • 通信作者: 尹智炜, 杨洪娟
  • 基金资助:
    国家自然科学基金(81900605, 81901404); 北京市自然科学基金(7204308); 河北省重点研发计划项目(18277746D)

Mechanisms of Yishen-Jianpi-Lishui recipe in the treatment of glomerulonephritis: a study based on network pharmacology and molecular docking

Meiling Jin1, Diangeng Li2, Weiguang Zhang3, Zhiwei Yin4,†(), Hongjuan Yang5,†()   

  1. 1. Department of Nephrology, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing 100020
    2. Department of Scientific Research, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing 100020
    3. Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing 100853
    4. Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing 100853; College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei Province
    5. Department of Nephrology of Integrated Chinese and Western Medicine, First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei Province; China
  • Received:2021-06-21 Published:2021-08-26
  • Corresponding author: Zhiwei Yin, Hongjuan Yang
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引用本文：

金美玲, 李典耕, 张伟光, 尹智炜, 杨洪娟. 基于网络药理学和分子对接研究益肾健脾利水方治疗肾小球肾炎的作用机制[J]. 中华肾病研究电子杂志, 2021, 10(04): 189-197.

Meiling Jin, Diangeng Li, Weiguang Zhang, Zhiwei Yin, Hongjuan Yang. Mechanisms of Yishen-Jianpi-Lishui recipe in the treatment of glomerulonephritis: a study based on network pharmacology and molecular docking[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2021, 10(04): 189-197.

目的

应用网络药理学及分子对接技术探究益肾健脾利水方(肾炎舒片)治疗肾小球肾炎的活性成分及分子机制。

方法

通过中药系统药理数据库和分析平台(TCMSP)查询方中主要的7味中药(苍术、茯苓、白茅根、人参、枸杞子、金银花、蒲公英)的主要活性成分，并对其靶点进行预测。检索GeneCards、OMIM、PharmGKB、TTD、DrugBank数据库。利用UniProt数据库注释所有靶标蛋白。将活性成分作用靶点和疾病靶点交集部分作为肾炎舒片治疗肾小球肾炎的潜在作用靶点，并利用GO数据库和KEGG数据库进行通路富集分析，将得到的核心有效成分与核心靶标进行分子对接。

结果

筛选出81个活性成分、219个基因靶点、肾小球肾炎相关靶点1 952个、116个肾炎舒片治疗肾小球肾炎的潜在靶点蛋白。GO富集分析结果提示：肾炎舒片治疗肾小球肾炎的潜在靶点蛋白，主要参与脂多糖反应、细菌源分子反应、氧化反应以及细胞化学压力反应等生物学过程。KEGG富集分析结果提示：可能的作用通路包括脂质和动脉粥样硬化通路、糖尿病并发症的AGE-RAGE信号通路、乙型肝炎相关通路以及卡波西肉瘤相关疱疹病毒感染通路等。蛋白互作(PPI)网络分析结果显示：肾炎舒片可通过MYC、JUN、MAPK8、FOS、NR3C1、TP53、MAPK14、IL-2、MAPK1、AKT1、TNF、RELA这12个关键靶点治疗肾小球肾炎。分子对接结果提示肾炎舒片主要活性成分与多种治疗肾小球肾炎靶点蛋白均有较好结合(S>4.5)。

结论

本研究结果提示益肾健脾利水方(肾炎舒片)治疗肾小球肾炎具有多成分、多靶点、多通路的特点，为进一步阐释其药理作用机制及开发新药奠定了研究基础。

关键词: 肾益健脾利水方, 肾炎舒片, 肾小球肾炎, 网络药理学, 分子对接
Objective

To explore the active ingredients and molecular mechanisms of Yishen-Jianpi-Lishui recipe (Shenyanshu tablet, SYST) in the treatment of glomerulonephritis by the network pharmacology and molecular docking methods.

Methods

Through the analysis platform of Traditional Chinese Medicine Systems Pharmacology (TCMSP), the main active ingredients of the 7 main Chinese medicines (Atractylodes, Poria, Imperata, ginseng, wolfberry, honeysuckle, and dandelion) in the recipe were queried, and their targets were also predicted. The databases were searched including the human gene database (GeneCards), the database of Online Mendelian Inheritance in Man (OMIM), the Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB), the Therapeutic Target Database (TTD), and the drug action target database (DrugBank). The UniProt database was used to annotate all targets proteins. The intersection of the active ingredients′ targets and diseases′ targets were taken as the potential targets for the treatment of glomerulonephritis by SYST, for which the gene ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were applied for the pathway enrichment analysis, and the core active ingredients and core targets obtained were analyzed with the molecular docking method.

Results

A total of 81 active ingredients, 219 gene targets, 1, 952 glomerulonephritis-related targets, and 116 potential targets proteins for the treatment of glomerulonephritis with SYST were screened out. The GO enrichment analysis results suggested that the potential targets proteins for the treatment of glomerulonephritis with SYST were mainly involved in the biological processes such as lipopolysaccharide reaction, bacterial-derived molecular reaction, oxidation reaction, and cytochemical pressure reaction. The KEGG enrichment analysis results suggested that possible pathways included the lipid and atherosclerosis pathways, the advanced glycation end products (AGEs) and the receptor for AGE (RAGE) signaling pathways for diabetic complications, hepatitis B-related pathways, and Kaposi′s sarcoma-related herpes virus infection pathways, etc. The Protein-Protein Interaction (PPI) network analysis showed that SYST could act in the treatment of glomerulonephritis through 12 key targets including MYC, JUN, MAPK8, FOS, NR3C1, TP53, MAPK14, IL-2, MAPK1, AKT1, TNF, and RELA. The molecular docking results indicated that the main active components of SYST combined well with a variety of targets proteins for the treatment of glomerulonephritis (S>4.5).

Conclusion

The results of this study suggested that SYST has the characteristics of multiple components, multiple targets, and multiple pathways in the treatment of glomerulonephritis, which laid a research foundation for further elucidating its pharmacological mechanism and developing new drugs.

Key words: Yishen-Jianpi-Lishui recipe, Shenyanshu tablet, Glomerulonephritis, Network pharmacology, Molecular docking
图1 肾小球肾炎相关靶蛋白筛选韦恩分析图
图2 肾炎舒片-肾小球肾炎靶标的韦恩分析图
表1 肾炎舒片治疗肾小球肾炎潜在靶蛋白的GO分析
GO分类 GO ID 描述 基因比例 P值
生物过程 GO：0032496 对脂多糖的反应 33/116 8.31E-31
生物过程 GO：0002237 对细菌来源分子的反应 33/116 6.88E-30
生物过程 GO：0006979 抗氧化反应 34/116 1.44E-27
生物过程 GO：0062197 细胞对化学应激的反应 31/116 4.65E-27
生物过程 GO：0072593 活性氧代谢过程 28/116 6.73E-26
生物过程 GO：0000302 对活性氧的反应 26/116 1.57E-25
生物过程 GO：0034599 细胞对氧化应激的反应 28/116 5.28E-25
生物过程 GO：0071222 细胞对脂多糖的反应 24/116 4.90E-24
生物过程 GO：0071216 细胞对生物刺激的反应 25/116 1.26E-23
生物过程 GO：0071219 细胞对细菌来源分子的反应 24/116 2.40E-23
细胞组分 GO：0045121 膜筏 18/116 9.25E-13
细胞组分 GO：0098857 膜微结构域 18/116 9.74E-13
细胞组分 GO：0098589 膜区 18/116 1.87E-12
细胞组分 GO：0044853 质膜筏 9/116 2.36E-08
细胞组分 GO：0005901 小窝 8/116 2.97E-08
细胞组分 GO：0090575 RNA聚合酶II转录调节复合物 9/116 4.98E-07
细胞组分 GO：0005667 转录调节复合物 13/116 1.06E-06
细胞组分 GO：0031983 囊腔 11/116 4.10E-06
细胞组分 GO：0000307 周期蛋白依赖性蛋白激酶全酶复合物 5/116 5.41E-06
细胞组分 GO：0034774 分泌颗粒内腔 10/116 2.22E-05
分子功能 GO：0140297 DNA结合转录因子结合 20/116 5.35E-14
分子功能 GO：0061629 RNA聚合酶Ⅱ特异性DNA结合转录因子 18/116 7.56E-14
分子功能 GO：0004879 核受体活性 10/116 8.68E-13
分子功能 GO：0098531 配体激活的转录因子活性 10/116 8.68E-13
分子功能 GO：0005126 细胞因子受体结合 16/116 1.52E-11
分子功能 GO：1901338 儿茶酚胺结合 6/116 1.61E-10
分子功能 GO：0003707 类固醇激素受体活性 7/116 2.00E-10
分子功能 GO：0005125 细胞因子活性 14/116 2.76E-10
分子功能 GO：0001223 转录辅激活结合 7/116 4.67E-10
分子功能 GO：0004252 丝氨酸蛋白酶肽链内切酶活性 11/116 9.94E-09
表2 肾炎舒片治疗肾小球肾炎潜在靶蛋白的KEGG分析
ID 描述 基因比例 P值
hsa04933 糖尿病并发症中的AGE-RAGE信号通路 30/111 2.57E-33
hsa05417 脂质和动脉粥样硬化 32/111 4.30E-25
hsa05161 乙型肝炎 28/111 8.76E-24
hsa04657 IL-17信号通路 23/111 2.86E-23
hsa05418 流体剪切应力与动脉粥样硬化 26/111 5.11E-23
hsa05167 卡波西肉瘤相关疱疹病毒感染 27/111 2.07E-20
hsa04668 TNF信号通路 22/111 5.04E-20
hsa05207 化学致癌-受体活化 26/111 3.44E-18
hsa05163 人巨细胞病毒感染 26/111 1.56E-17
hsa05215 前列腺癌 19/111 2.32E-17
hsa04625 C型凝集素受体信号通路 19/111 9.26E-17
hsa05140 利什曼病 17/111 1.47E-16
hsa01522 内分泌抵抗 18/111 5.78E-16
hsa05142 美洲锥虫病 18/111 1.22E-15
hsa05160 丙型肝炎 21/111 1.45E-15
hsa05133 百日咳 16/111 2.76E-15
hsa04659 Th17细胞分化 18/111 2.95E-15
hsa05169 EB病毒感染 22/111 2.30E-14
hsa04620 Toll样受体信号通路 17/111 3.06E-14
hsa05205 蛋白聚糖在癌症 22/111 3.14E-14
表3 肾炎舒片治疗肾小球肾炎的核心靶蛋白的KEGG分析
ID 描述 P值 基因数目
hsa05161 乙型肝炎 4.90E-16 10
hsa05142 美洲锥虫病 1.18E-15 9
hsa04660 T细胞受体信号通路 1.41E-15 9
hsa05166 人类T细胞白血病病毒1感染 1.06E-14 10
hsa05135 鼠疫感染 1.82E-14 9
hsa04010 MAPK信号通路 2.09E-13 10
hsa04620 Toll样受体信号通路 2.65E-13 8
hsa04625 C型凝集素受体信号通路 2.65E-13 8
hsa05167 卡波西肉瘤相关疱疹病毒感染 4.42E-13 9
hsa04668 TNF信号通路 4.87E-13 8
hsa05417 脂质动脉粥样硬化 1.13E-12 9
hsa04380 破骨细胞分化 1.45E-12 8
hsa04210 细胞凋亡 2.38E-12 8
hsa05418 流体剪切应力与动脉粥样硬化 2.85E-12 8
hsa05133 百日咳 3.66E-12 7
hsa05132 沙门氏菌感染 4.28E-12 9
hsa05210 结肠直肠癌 8.94E-12 7
hsa04658 Th1和Th2细胞分化 1.45E-11 7
hsa04657 IL-17信号通路 1.70E-11 7
hsa01522 内分泌抵抗 2.29E-11 7
图3 肾炎舒片治疗肾小球肾炎的蛋白-蛋白互作网络图
图4 肾炎舒片治疗肾小球肾炎的核心蛋白的筛选
图5 草药-活性成分-核心靶标网络构建
图6 肾炎舒片治疗肾小球肾炎核心靶标在MAPK信号通路富集图
表4 肾炎舒片活性分子与肾小球肾炎核心靶标分子对接结果
活性成分 靶标基因名称 PDB ID 结合能(kcal/mol)
山柰酚 MAPK8 P45983 -8.3
  AKT1 P31749 -9.9
  TNF P01375 -9.9
  JUN P05412 -8.8
槲皮苷 FOS P01100 -8.7
  TP53 P04637 -8.8
  IL2 P60568 -9.0
  MAPK1 P28482 -8.7
  AKT1 P31749 -9.9
  TNF P01375 -10.0
  JUN P05412 -8.6
  MYC P01106 -6.8
黄岑素 FOS P01100 -9.6
  TP53 P04637 -8.5
  AKT1 P31749 -10.0
人参二醇 NR3C1 P04150 -8.4
汉黄芩素 TP53 P04637 -8.9
  AKT1 P31749 -9.7
  TNF P01375 -9.8
  MAPK14 Q16539 -8.1
  JUN P05412 -7.4
薯蓣皂苷配基 TP53 P04637 -10.1
  AKT1 P31749 -7.7
毛地黄黄酮 TP53 P04637 -8.6
  IL2 P60568 -8.8
  MAPK1 P28482 -9.0
  AKT1 P31749 -10.1
  TNF P01375 -10.3
  JUN P05412 -9.0
β胡萝卜素 AKT1 P31749 -8.9
  JUN P05412 -7.6
  MYC P01106 -6.4
人参皂苷 TNF P01375 -9.9
3′_甲氧基大豆黄素 MAPK14 Q16539 -8.3
黄豆黄素 MAPK14 Q16539 -8.3
β谷甾醇 JUN P05412 -8.0
图7 活性分子与靶标蛋白分子对接示意图
[1]
GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 [J]. Lancet, 2020, 395 (10225): 709-733.
[2]
Yang C, Gao B, Zhao X, et al. Executive summary for China Kidney Disease Network (CK-NET) 2016 annual data report [J]. Kidney Int, 2020, 98 (6): 1419-1423.
[3]
Goncalves GFB, Silva MEM, Sampaio FJB, et al. Quercetin as a nephroprotector after warm ischemia: histomorphometric evaluation in a rodent model [J]. Int Braz J Urol, 2021, 47 (4): 796-802.
[4]
Rahdar A, Hasanein P, Bilal M, et al. Quercetin-loaded F127 nanomicelles: antioxidant activity and protection against renal injury induced by gentamicin in rats [J]. Life Sci, 2021, 276: 119420.
[5]
Lu S, Zhou S, Chen J, et al. Quercetin nanoparticle ameliorates lipopolysaccharide-triggered renal inflammatory impairment by regulation of Sirt1/NF-κB pathway [J]. J Biomed Nanotechnol, 2021, 17 (2): 230-241.
[6]
Al-Rasheed NM, Faddah LM, Mohamed AM, et al. Potential impact of quercetin and idebenone against immuno-inflammatory and oxidative renal damage induced in rats by titanium dioxide nanoparticles toxicity [J]. J Oleo Sci, 2013, 62 (11): 961-971.
[7]
Kim GT, Lee SH, Kim JI, et al. Quercetin regulates the sestrin 2-AMPK-p38MAPK signaling pathway and induces apoptosis by increasing the generation of intracellular ROS in a p53-independent manner [J]. Int J Mol Med, 2014, 33 (4): 863-869.
[8]
Sharma D, Kumar Tekade R, Kalia K. Kaempferol in ameliorating diabetes-induced fibrosis and renal damage: an in vitro and in vivo study in diabetic nephropathy mice model [J]. Phytomedicine, 2020, 76: 153235.
[9]
Ji X, Cao J, Zhang L, et al. Kaempferol protects renal fibrosis through activating the BMP-7-Smad1/5 signaling pathway [J]. Biol Pharm Bull, 2020, 43(3): 533-539.
[10]
Wang Z, Sun W, Sun X, et al. Kaempferol ameliorates cisplatin induced nephrotoxicity by modulating oxidative stress, inflammation and apoptosis via ERK and NF-κB pathways [J]. AMB Express, 2020, 10 (1): 58.
[11]
Owumi SE, Lewu DO, Arunsi UO, et al. Luteolin attenuates doxorubicin-induced derangements of liver and kidney by reducing oxidative and inflammatory stress to suppress apoptosis [J]. Hum Exp Toxicol, 2021, Epub ahead of print.
[12]
Zhang M, He L, Liu J, et al. Luteolin attenuates diabetic nephropathy through suppressing inflammatory response and oxidative stress by inhibiting STAT3 pathway [J]. Exp Clin Endocrinol Diabetes, 2020, Epub ahead of print.
[13]
Kalbolandi SM, Gorji AV, Babaahmadi-Rezaei H, et al. Luteolin confers renoprotection against ischemia-reperfusion injury via involving Nrf2 pathway and regulating miR320 [J]. Mol Biol Rep, 2019, 46 (4): 4039-4047.
[14]
Yu P, Wellmann U, Kunder S, et al. Toll-like receptor 9-independent aggravation of glomerulonephritis in a novel model of SLE [J]. Int Immunol, 2006, 18(8): 1211-1219.
[15]
Wornle M, Schmid H, Banas B, et al. Novel role of Toll-like receptor 3 in hepatitis C-associated glomerulonephritis [J]. Am J Pathol, 2006, 168 (2): 370-385.
[16]
Liu Q, Imaizumi T, Kawaguchi S, et al. Toll-like receptor 3 signaling contributes to regional neutrophil recruitment in cultured human glomerular endothelial cells [J]. Nephron, 2018, 139 (4): 349-358.
[17]
Li DD, Bechara R, Ramani K, et al. RTEC-intrinsic IL-17-driven inflammatory circuit amplifies antibody-induced glomerulonephritis and is constrained by Regnase-1 [J]. JCI Insight, 2021, 6 (13):147505.
[18]
Pisitkun P, Ha HL, Wang H, et al. Interleukin-17 cytokines are critical in development of fatal lupus glomerulonephritis [J]. Immunity, 2012, 37 (6): 1104-1115.
[19]
Chen X, Sun M. Identification of key genes, pathways and potential therapeutic agents for IgA nephropathy using an integrated bioinformatics analysis [J]. J Renin Angiotensin Aldosterone Syst, 2020, 21(2): 1470320320919635.
[20]
Wang Q, Wang X, Ye Z. Screening and bioinformatics analysis of IgA nephropathy gene based on GEO databases [J]. Biomed Res Int, 2019, 2019: 8794013.
[21]
Li Y, Liu Q, Ou ST, et al. Research on mechanism of MAPK signal pathway induced by BMSCs for the proteinuria of rat′s kidney, glomerulosclerosis and activity of RAS [J]. Eur Rev Med Pharmacol Sci, 2021, 25 (2): 795-803.
[22]
Ponticelli C, Locatelli F. Glucocorticoids in the treatment of glomerular diseases: pitfalls and pearls [J]. Clin J Am Soc Nephrol, 2018, 13 (5): 815-822.
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