Medication Regularity for Chronic Renal Failure and Underlying Mechanism Based on Data Mining， Network Pharmacology， and Molecular Docking

Yi FU; Xin LI; Ying ZHU; Zhao-dong WU; Bang-ming CHEN; Yi FU; Yong-fang LIU; Meng SHU

doi:10.13422/j.cnki.syfjx.20220319

您当前的位置：

首页 >

文章列表页 >

Medication Regularity for Chronic Renal Failure and Underlying Mechanism Based on Data Mining， Network Pharmacology， and Molecular Docking

更新时间：2022-02-15

- Medication Regularity for Chronic Renal Failure and Underlying Mechanism Based on Data Mining， Network Pharmacology， and Molecular Docking
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 6, Pages: 151-158(2022)
- 作者机构：
  
  1.湖南中医药大学，长沙 410007
  2.江西省中医肾病临床医学研究中心/九江市中医院，江西九江 332001
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20220319
  CLC： R284.2;R285;R289;R22;R2-031;R33
- Received：02 November 2021，
  
  Published Online：25 January 2022，
  
  Published：20 March 2022
- 稿件说明：
移动端阅览
傅奕,李鑫,朱莹等.慢性肾功能衰竭用药规律及潜在机制分析[J].中国实验方剂学杂志,2022,28(06):151-158.

FU Yi,LI Xin,ZHU Ying,et al.Medication Regularity for Chronic Renal Failure and Underlying Mechanism Based on Data Mining， Network Pharmacology， and Molecular Docking[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(06):151-158.
傅奕,李鑫,朱莹等.慢性肾功能衰竭用药规律及潜在机制分析[J].中国实验方剂学杂志,2022,28(06):151-158. DOI： 10.13422/j.cnki.syfjx.20220319.

FU Yi,LI Xin,ZHU Ying,et al.Medication Regularity for Chronic Renal Failure and Underlying Mechanism Based on Data Mining， Network Pharmacology， and Molecular Docking[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(06):151-158. DOI： 10.13422/j.cnki.syfjx.20220319.

摘要

目的

阐释江西省名中医吴兆东主任医师治疗慢性肾功能衰竭的遣药组方规律，并探讨潜在新方组合的潜在作用机制。

方法

收集2019年7月至2021年7月吴兆东主任门诊处方，运用中医传承辅助平台（V2.5）进行数据挖掘，分析处方药物的用药频次、药物关联，并得出潜在中药新方组合。运用中药系统药理学数据库及分析平台（TCMSP）、STRING及京都基因与基因组百科全书（KEGG）对“新处方”中药物靶标间相互作用关系进行分析，并进行分子对接验证和实验验证。

结果

①共筛选出200首处方，包含217味中药，演化得到8个潜在新方组合：处方1苦杏仁-黄芪-桔梗-当归-土茯苓-炒白术；处方2防风-荆芥-地肤子-紫菀-薄荷；处方3苦杏仁-紫菀-桔梗-枇杷叶-炙麻黄；处方4紫苏梗-党参-黄连-太子参；处方5旱莲草-炙黄芪-贯众-金樱子-薏苡仁-女贞子；处方6泽兰-忍冬藤-络石藤-泽泻；处方7黄芩-水蛭-赤芍-枇杷叶-北沙参；处方8甘草-玄参-野菊花-土茯苓-六月雪。②筛选出潜在新处方组合（新方1）的主要化学成分有18种；③预测到新方1活性成分的作用靶标80个，映射后得出新方1治疗CRF37个潜在靶标［（如白细胞介素（IL）-6、血管内皮生长因子（VEGF）、半胱氨酸天冬氨酸蛋白水解酶（Caspase）-3、一氧化氮合酶（NOS）3、缺氧诱导因子（HIF）-1等］；④中药-疾病靶标涉及的KEGG通路主要包括脂质和动脉粥样硬化、NF-

B、Toll样受体、HIF1信号通路。⑤新方1显著降低CRF大鼠血清肌酐、尿素氮，提高肾组织NO、NOS3含量。

结论

新方1中药组合显示了多成分、多靶点的药物作用特点，其机制可能与其抑制肾纤维化、抗炎、改善肠道微生态、改善肾脏缺氧缺血有关。

Abstract

Objective

To clarify the medication regularity of WU Zhao-dong，a famous chief physician in traditional Chinese medicine （TCM） of Jiangxi province， and investigate the potential mechanism of potential new prescriptions against chronic renal failure （CRF）.

Method

The outpatient prescriptions of WU Zhao-dong from July 2019 to July 2021 were collected. Data mining was carried out by using the Traditional Chinese Medicine Inheritance Auxiliary Platform （V 2.5） to analyze the medication frequency and drug association and obtain potential new prescriptions. The interaction between drug targets in new prescriptions was analyzed by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），STRING，and Kyoto Encyclopedia of Genes and Genomes（KEGG）， followed by verification by molecular docking and experiments.

Result

A total of 200 prescriptions were screened out， with 217 Chinese medicinal drugs involved， and eight new potential prescriptions were derived. To be specific， Prescription 1： Armeniacae Semen Amarum-Astragali Radix

Platycodonis Radix-Angelicae Sinensis Radix-Smilacis Glabrae Rhizoma

fried Atractylodis Macrocephalae Rhizoma， Prescription 2： Saposhnikoviae Radix-Schizonepetae Herba-Kochiae Fructus-Asteris Radix et Rhizoma-Menthae Haplocalycis Herba，Prescription 3：Armeniacae Semen Amarum-Asteris Radix et Rhizoma-Platycodonis Radix-Eriobotryae Folium-prepared Ephedrae Herba， Prescription 4：Perillae Caulis-Codonopsis Radix-Coptidis Rhizoma-Pseudostellariae Radix， Prescription 5：Ecliptae Herba-Astragali Radix Praeparata Cum Melle-Dryopteridis Crassirhizomatis Rhizoma-Rosae Laevigatae Fructus-Coicis Semen-Ligustri Lucidi Fructus， Prescription 6： Lycopi Herba-Lonice Raejaponicae Caulis-Trachelospermi Caulis et Folium-Alismatis Rhizoma， Prescription 7：Scutellariae Radix-Hirudo-Paeoniae Radix Rubra-Eriobotryae Folium-Glehniae Radix， Prescription 8：Glycyrrhizae Radix et Rhizoma-Scrophulariae Radix-Chrysanthemi Indici Flos-Smilacis Glabrae Rhizoma- Serissae Herba. In Prescription 1，18 main chemical components were screened out. Eighty targets of active components of Prescription 1 were predicted， and 37 potential targets for the treatment of CRF were obtained， including interleukin （IL）-6， vascular endothelial growth factor （VEGF）， cysteinyl aspartate-specific protease-3 （Caspase-3）， nitric oxide synthase 3 （NOS3）， and hypoxia-inducible factor-1 （HIF-1）. The KEGG pathways involved in the targets of Chinese medicinal drugs and disease mainly included the signaling pathways of lipid and atherosclerosis，NF-

B， Toll-like receptors， and HIF-1. Prescription 1 significantly decreased serum creatinine and urea nitrogen， and increased the content of NO and NOS3 in renal tissues of CRF rats.

Conclusion

Prescription 1 shows the multi-component and multi-target characteristics of action，and its mechanism may be related to its inhibition of renal fibrosis，anti-inflammation，improvement of intestinal microecology，and improvement of renal hypoxia and ischemia.

关键词

Keywords

references

LV J C ， ZHANG L X . Prevalence and disease burden of chronic kidney disease ［J］. Adv Exp Med Biol ， 2019 ， 1165 ： 3 - 15 .

HEERSPINK H ， STEFÁNSSON B V ， CORREA-ROTTER R ， et al . Dapagliflozin in patients with chronic kidney disease ［J］. N Engl J Med ， 2020 ， 383 （ 15 ）： 1436 - 1446 .

RUIZ-ORTEGA M ， RAYEGO-MATEOS S ， LAMAS S ， et al . Targeting the progression of chronic kidney disease ［J］. Nat Rev Nephrol ， 2020 ， 16 （ 5 ）： 269 - 288 .

张荣东，林莺，刘利华 . 国医大师邹燕勤从肾虚湿瘀论治慢性肾脏病经验［J］. 中国中医药信息杂志， 2021 ， 28 （ 6 ）： 109 - 111 .

刘新，肖春霞，张星平，等 . 张星平运用元气理论辨治慢性肾功能衰竭经验［J］. 中华中医药杂志， 2019 ， 34 （ 10 ）： 4639 - 4642 .

樊威伟 . 张大宁从虚、瘀、湿、逆论治慢性肾功能衰竭经验［J］. 中医杂志， 2019 ， 60 （ 11 ）： 916 - 919 .

张宏，王旭昀，刘美奇，等 . 国医大师吕仁和教授治疗慢性肾功能衰竭经验总结［J］. 西部中医药， 2020 ， 33 （ 2 ）： 37 - 39 .

国家药品食品监督局 . 中药新药临床研究指导原则（试行）［M］. 北京：中国医药科技出版社， 2002 ： 164 .

余柯娜，麻志恒，钟利平，等 . SD大鼠与C57小鼠5/6肾切除慢性肾功能衰竭模型的比较［J］. 中国比较医学杂志， 2015 ， 25 （ 8 ）： 48 - 53，87 .

苏醒，徐建龙，包蓓艳 . 黄芪当归汤辅助治疗慢性肾功能衰竭（3期～4期）的临床研究［J］. 中华中医药学刊， 2015 ， 33 （ 2 ）： 495 - 497 .

刘婕，冯兴中 . 吕仁和治疗慢性肾功能衰竭药对挖掘与浅析［J］. 世界中医药， 2017 ， 12 （ 3 ）： 606 - 609 .

顾思浩，孔维崧，张彤，等 . 白术的化学成分与药理作用及复方临床应用进展［J］. 中华中医药学刊， 2020 ， 38 （ 1 ）： 69 - 73 .

文雯，程祖强，侯凯 . 基于肠道微生态的白术散作用机制研究进展［J］. 微生物学通报， 2021 ： 1 - 11 .

夏平，张露，刘琼，等 . 基于"肾虚湿瘀"理论治疗慢性肾脏病的核心方药分析［J］. 世界科学技术—中医药现代化， 2019 ， 21 （ 6 ）： 1075 - 1084 .

范为民，李艳 . 国医大师李济仁教授辨治肾系疾病经验撷要［J］. 时珍国医国药， 2016 ， 27 （ 12 ）： 3027 - 3029 .

易志忠，陈国忠，欧智海，等 . 基于"升降相因"探讨脏腑气机升降及药对配伍理论［J］. 中国中医基础医学杂志， 2021 ， 27 （ 2 ）： 228 - 229，239 .

LIU Y ， LEI L ， WANG X ， et al . Plasma cholesterol-raising potency of dietary free cholesterol versus cholesteryl ester and effect of β -sitosterol ［J］. Food Chem ， 2015 ， 169 ： 277 - 282 .

LIU R ， HAO D ， XU W ， et al . β -Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice ［J］. Pharm Biol ， 2019 ， 57 （ 1 ）： 161 - 168 .

ANTWI A O ， OBIRI D D ， OSAFO N ， et al . Stigmasterol inhibits lipopolysaccharide-induced innate immune responses in murine models ［J］. Int Immunopharmacol ， 2017 ， 53 ： 105 - 113 .

KANGSAMAKSIN T ， CHAITHONGYOT S ， WOOTTHICHAIRANGSAN C ， et al . Lupeol and stigmasterol suppress tumor angiogenesis and inhibit cholangiocarcinoma growth in mice via downregulation of tumor necrosis factor- α ［J］. PLoS One ， 2017 ， 12 （ 12 ）： e0189628 .

LIU N ， FENG J ， LU X ， et al . Isorhamnetin inhibits liver fibrosis by reducing autophagy and inhibiting extracellular matrix formation via the TGF-1/Smad3 and TGF-1/p38 MAPK pathways ［J］. Int Immunopharmacol ， 2019 ， 2019 ： 6175091 .

LIU C ， LIU H ， LU C ， et al . Kaempferol attenuates imiquimod-induced psoriatic skin inflammation in a mouse model ［J］. Clin Exp Immunol ， 2019 ， 198 （ 3 ）： 403 - 415 .

IMRAN M ， RAUF A ， SHAH Z A ， et al . Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol：A comprehensive review ［J］. Phytother Res ， 2019 ， 33 （ 2 ）： 263 - 275 .

FEIGERLOVÁ E ， BATTAGLIA-HSU S F . IL-6 signaling in diabetic nephropathy：From pathophysiology to therapeutic perspectives ［J］. Cytokine Growth Factor Rev ， 2017 ， 37 ： 57 - 65 .

ZHANG Y ， ZHANG Y . lncRNA ZFAS1 improves neuronal injury and inhibits inflammation，oxidative stress，and apoptosis by sponging miR-582 and upregulating NOS3 expression in cerebral ischemia/reperfusion injury ［J］. Inflammation ， 2020 ， 43 （ 4 ）： 1337 - 1350 .

WEN S ， WANG Z H ， ZHANG C X ， et al . Caspase-3 promotes diabetic kidney disease through gasdermin E-mediated progression to secondary necrosis during apoptosis ［J］. Diabetes Metab Syndr Obes ， 2020 ， 13 ： 313 - 323 .

LAWAN A ， BENNETT A M . Mitogen-activated protein kinase regulation in hepatic metabolism ［J］. Trends Endocrinol Metab ， 2017 ， 28 （ 12 ）： 868 - 878 .

POZNYAK A ， GRECHKO AV ， POGGIO P ， et al . The Diabetes mellitus-atherosclerosis connection：the role of lipid and glucose metabolism and chronic inflammation ［J］. Int J Mol Sci ， 2020 ， 21 （ 5 ）： 1835 .

LIU W ， ZHU H ， FANG H . Propofol potentiates sevoflurane-induced inhibition of nuclear factor- κ B-mediated inflammatory responses and regulation of mitogen-activated protein kinases pathways via toll-like receptor 4 signaling in lipopolysaccharide-induced acute lung injury in mice ［J］. Am J Med Sci ， 2017 ， 354 （ 5 ）： 493 - 505 .

FENG Q ， LIU D ， LU Y ， et al . The interplay of renin-angiotensin system and Toll-like receptor 4 in the inflammation of diabetic nephropathy ［J］. J Immunol Res ， 2020 ， 2020 （ 1 ）： 6193407 .

唐群，吴华，张熙，等 . 六味地黄汤对慢性肾衰模型大鼠PHD2和HIF-1 α 表达的影响［J］. 北京中医药大学学报， 2017 ， 40 （ 4 ）： 290 - 296 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mahoniae Caulis Alkaloids Ameliorate Depression by Regulating Synaptic Plasticity via cAMP Pathway

Analysis of Potential Active Components and Molecular Mechanism of Baoxin Granules Regulating Ferroptosis in Treatment of Heart Failure

Effect and Mechanism of Angelicae Sinensis Radix-Polygonati Rhizoma Herb Pair in Treatment of Simple Obesity

Screening of Anti-breast Cancer Active Ingredients in Famous Classical Formula Yanghetang

Analysis on Pharmacodynamic Material Basis and Mechanism of Famous Classical Formula Renshen Wuweizi Tang in Treatment of Spleen and Lung Qi Deficiency Syndrome

Related Author

HE Junhui

JIA Chunlian

LAI Kedao

ZHOU Guili

ZHOU Rongfei

LI Yi

LI Dongmei

XIE Jiaxiu

Related Institution

Key Laboratory of Chemistry and Engineering of Forest Products， National Ethnic Affairs Commission， Guangxi Key Laboratory of Chemistry and Engineering of Forest Products/Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products， School of Chemistry and Chemical Engineering， Guangxi Minzu University

Guangxi Key Laboratory of Chinese Medicine Quality Standard， Guangxi Institute of Chinese Medicine and Pharmaceutical Science

Guangxi Medical University

State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs， Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences

Jiangxi Province Key Laboratory of Traditional Chinese Medicine（TCM） Pharmacology，Institute of TCM Health Industry，China Academy of Chinese Medical Sciences

AI问答

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰