Exploring Mechanism of Renshen Guben Oral Liquids in Treating Renal Fibrosis Based on Metabolomics and Network Pharmacology

JIANG Hong; ZHANG Tong; ZHANG Junhong; QIN Yuewen; XIE Dongmei; WANG Ping; XU Haiyu

doi:10.13422/j.cnki.syfjx.20230666

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Exploring Mechanism of Renshen Guben Oral Liquids in Treating Renal Fibrosis Based on Metabolomics and Network Pharmacology

更新时间：2023-05-16

- Exploring Mechanism of Renshen Guben Oral Liquids in Treating Renal Fibrosis Based on Metabolomics and Network Pharmacology
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 12, Pages: 142-148(2023)
- 作者机构：
  
  1.安徽中医药大学，合肥 230012
  2.中国中医科学院中药研究所，北京 100700
  3.中国中医科学院国家药品监督管理局中医药研究与评价重点实验室，北京 100700
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230666
  CLC： R22;R969.1;R28;O657
- Published：20 June 2023，
  
  Published Online：14 March 2023，
  
  Received：26 December 2022，
- 稿件说明：
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江红,张瞳,张俊红等.基于代谢组学和网络药理学探究人参固本口服液治疗肾纤维化的作用机制[J].中国实验方剂学杂志,2023,29(12):142-148.

JIANG Hong,ZHANG Tong,ZHANG Junhong,et al.Exploring Mechanism of Renshen Guben Oral Liquids in Treating Renal Fibrosis Based on Metabolomics and Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(12):142-148.
江红,张瞳,张俊红等.基于代谢组学和网络药理学探究人参固本口服液治疗肾纤维化的作用机制[J].中国实验方剂学杂志,2023,29(12):142-148. DOI： 10.13422/j.cnki.syfjx.20230666.

JIANG Hong,ZHANG Tong,ZHANG Junhong,et al.Exploring Mechanism of Renshen Guben Oral Liquids in Treating Renal Fibrosis Based on Metabolomics and Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(12):142-148. DOI： 10.13422/j.cnki.syfjx.20230666.

摘要

目的

基于代谢组学和网络药理学开展人参固本口服液治疗肾纤维化小鼠的作用机制研究。

方法

将36只C57BL/6小鼠随机分为空白组、模型组、人参固本口服液组，除空白组外，均采用单侧输尿管结扎术制备小鼠单侧输尿管梗阻模型。术后人参固本口服液组灌胃给予4.2 g·kg

-1

浸膏粉的水溶液，连续给药14 d，空白组和模型组灌胃给予等量蒸馏水。末次给药后，收集尿液，采用超高效液相色谱-三重四极杆-串联质谱法（UPLC-QQQ-MS/MS）进行检测，以0.1%甲酸水溶液为流动相A，乙腈-异丙醇（70∶30）为流动相B，梯度洗脱（0~1 min，5%B；1~5 min，5%~30%B；5~9 min，30%~50%B；9~11 min，50%~78%B；11~13.5 min，78%~95%B；13.5~14 min，95%~100%B；14~16 min，100%B；16~16.1 min，100%~5%B；16.1~18 min，5%B），柱温40 ℃，流速0.4 mL·min

-1

，电喷雾离子源（ESI），采集范围

50~900；通过网络药理学对人参固本口服液成分的靶点与肾纤维化的靶点进行交互分析，网络拓扑分析筛选出关键成分和关键靶点，采用功能注释生物信息学分析数据库（DAVID）预测人参固本口服液治疗肾纤维化的信号通路。

结果

共鉴定出人参固本口服液治疗肾纤维化的7个差异代谢物，涉及8条代谢通路。网络药理学分析发现，人参固本口服液中36个核心成分与该7个差异代谢物相关，主要为人参皂苷类、三七皂苷类及核苷酸类化合物。基于“药材-成分-靶点-通路”网络，共筛选出23个关键靶点，与差异代谢物共同涉及亚油酸代谢、精氨酸生物合成、三羧酸循环（TCA）、精氨酸与脯氨酸代谢等通路。

结论

该研究基于代谢组学与网络药理学技术，确定了人参固本口服液治疗肾纤维化中7个差异代谢物、36个潜在药效成分、23个核心靶点和4条关键通路，可为该药的临床应用及机制研究提供实验依据。

Abstract

Objective

To investigate the mechanism of Renshen Guben oral liquids（RGOL） in treatment of mice with renal fibrosis based on metabolomics and network pharmacology.

Method

C57BL/6 mice were randomly divided into control group， model group and RGOL group， 12 mice in each group. Except for the control group， mice in the other groups were induced into unilateral ureteral obstruction（UUO） model by UUO. After preparation of the model， an aqueous solution of 4.2 g·kg

-1

extract powder was administered by gavage to RGOL group for 14 d， and an equal amount of distilled water was administered by gavage to the control and model groups. After the last administration on the 14

day， urine was collected and detected by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QQQ-MS/MS） with 0.1% formic acid aqueous solution as mobile phase A， and acetonitrile-isopropanol（70∶30） as mobile phase B for gradient elution（0-1 min， 5%B； 1-5 min， 5%-30%B； 5-9 min， 30%-50%B； 9-11 min， 50%-78%B； 11-13.5 min， 78%-95%B； 13.5-14 min， 95%-100%B； 14-16 min， 100%B； 16-16.1 min， 100%-5%B； 16.1-18 min， 5%B）， column temperature of 40 ℃， flow rate of 0.4 mL·min

-1

， electrospray ionization（ESI）， collection range of

50-900. Through network pharmacology， the targets of components in RGOL and the targets of renal fibrosis were analyzed interactively， and the key components and key targets were screened by network topology analysis， and DAVID platform was used to predict the signaling pathways of RGOL for the treatment of renal fibrosis.

Result

A total of 7 differential metabolites involving 8 metabolic pathways were identified in RGOL for the treatment of renal fibrosis. The network pharmacology revealed that 36 key components in RGOL were related to 7 differential metabolites， mainly ginsenosides， notoginsenosides and nucleotides. Based on the herbs-components-targets-pathways network， a total of 23 key targets related to the treatment of renal fibrosis by RGOL were highlighted， which together with the differential metabolites were involved in linoleic acid metabolism， arginine biosynthesis， tricarboxylic acid cycle（TCA）， arginine and proline metabolism and other pathways.

Conclusion

Based on metabolomics and network pharmacology， this study preliminarily identified 7 differential metabolites， 36 potential pharmacodynamic components and 23 key targets and 4 key pathways in RGOL for the treatment of renal fibrosis， providing an experimental basis for the clinical application and mechanism study of this preparation.

关键词

人参固本口服液代谢组学网络药理学肾纤维化超高效液相色谱-三重四极杆-串联质谱联用法（UPLC-QQQ-MS/MS）代谢通路

Keywords

Renshen Guben oral liquidsmetabolomicsnetwork pharmacologyrenal fibrosisultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QQQ-MS/MS）metabolic pathways

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