Study on Mechanism of Reducing Excess Fire of Liver and Gallbladder of Bile Processed Coptidis Rhizoma Based on UPLC-Q-Orbitrap HRMS and Network Pharmacology

Qian RAN; Guan-hua LOU; Hai-rong ZENG; Qin-wan HUANG; Jin WANG

doi:10.13422/j.cnki.syfjx.20201057

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Study on Mechanism of Reducing Excess Fire of Liver and Gallbladder of Bile Processed Coptidis Rhizoma Based on UPLC-Q-Orbitrap HRMS and Network Pharmacology

Pharmacy Fundamentals | 更新时间：2020-08-11

- Study on Mechanism of Reducing Excess Fire of Liver and Gallbladder of Bile Processed Coptidis Rhizoma Based on UPLC-Q-Orbitrap HRMS and Network Pharmacology
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 13, Pages: 181-189(2020)
- 作者机构：
  
  成都中医药大学药学院，成都 611137
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20201057
  CLC： R22;R96;R28;O657.6;C37
- Published Online：11 February 2020，
  
  Published：05 July 2020
- 稿件说明：
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冉倩,楼冠华,曾海蓉等.基于UPLC-Q-Orbitrap HRMS和网络药理学分析胆黄连的泻肝胆实火机制[J].中国实验方剂学杂志,2020,26(13):181-189.

RAN Qian,LOU Guan-hua,ZENG Hai-rong,et al.Study on Mechanism of Reducing Excess Fire of Liver and Gallbladder of Bile Processed Coptidis Rhizoma Based on UPLC-Q-Orbitrap HRMS and Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(13):181-189.
冉倩,楼冠华,曾海蓉等.基于UPLC-Q-Orbitrap HRMS和网络药理学分析胆黄连的泻肝胆实火机制[J].中国实验方剂学杂志,2020,26(13):181-189. DOI： 10.13422/j.cnki.syfjx.20201057.

RAN Qian,LOU Guan-hua,ZENG Hai-rong,et al.Study on Mechanism of Reducing Excess Fire of Liver and Gallbladder of Bile Processed Coptidis Rhizoma Based on UPLC-Q-Orbitrap HRMS and Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(13):181-189. DOI： 10.13422/j.cnki.syfjx.20201057.

摘要

目的

基于UPLC-Q-Orbitrap HRMS和网络药理学阐明胆黄连泻肝胆实火的物质基础、作用机制及炮制原理。

方法

采用UPLC-Q-Orbitrap HRMS技术鉴定胆黄连的化学成分，流动相0.1%甲酸水溶液（A）-乙腈（B）梯度洗脱（0~20 min，5%~80%B；20~30 min，80%~95%B；30~30.1 min，95%~5%B；30.1~35 min，5%B），流速0.2 mL·min

-1

，电喷雾离子源（ESI），正、负离子模式扫描，扫描范围

100~1 500。在此基础上，选择肝胆实火的临床表现和病因作为媒介，利用在线数据库对胆黄连泻肝胆实火的潜在药效物质基础、作用靶点和作用特征进行预测分析。从炮制后新增活性成分的作用特点入手，运用网络药理学探究胆汁制黄连的炮制原理。

结果

分析并鉴定了胆黄连中19种成分，其中6种为炮制后新增的胆酸类成分。药物本身的生物碱类成分巴马汀、甲基黄连碱、表小檗碱、小檗碱、小檗红碱、黄连碱、药根碱和新增的胆酸类成分甘氨猪去氧胆酸、牛磺猪去氧胆酸、猪去氧胆酸、甘氨鹅去氧胆酸、牛磺鹅去氧胆酸是胆黄连潜在的药效物质基础。预测筛选出与胆黄连泻肝胆实火作用相关靶点66个。胆汁赋予的胆酸类成分与黄连的生物碱成分有16个共同作用靶点和多条相同的信号通路，且肝胆实火的多个病灶为胆酸类成分的靶器官。胆黄连通过作用于白蛋白（ALB），半胱氨酸天冬氨酸蛋白酶-3（CASP3），丝裂原活化蛋白激酶14（MAPK14），糖皮质激素受体（NR3C1）等靶点和白细胞介素-17（IL-17）信号通路，磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路，MAPK信号通路等通路发挥对肝胆实火证的治疗作用。

结论

胆黄连呈现了多成分、多靶点、多途径泻肝胆实火的作用特点，且炮制辅料胆汁和炮制药物黄连具有协同作用，胆汁可增强药物在病灶的作用强度，印证了黄连经胆汁制后泻肝胆实火作用增强的炮制理论。

Abstract

Objective

Based on UPLC-Q-Orbitrap HRMS and network pharmacology

the material basis

processing principle and molecular mechanism of bile processed Coptidis Rhizoma

(BPRC) for reducing excess fire of liver and gallbladder were elucidated.

Method

The chemical ingredients of BPRC were analyzed by UPLC-Q-Orbitrap HRMS. Chromatographic separation was achieved with 0.1% formic acid solution (A)-acetonitrile (B) as the mobile phase in gradient elution (0-20 min

5%-80%B; 20-30 min

80%-95%B; 30-30.1 min

95%-5%B; 30.1-35 min

95%-5%B). The flow rate was 0.2 mL·min

-1

electrospray ionization (ESI) was applied and operated in positive and negative ion modes

the acquisition range was

100-1 500. Based on the clinical manifestations and pathogenic factors of excess fire of liver and gallbladder

the potential effective ingredients

targets and functional characteristics of BPRC were predicted and analyzed by online database. Based on the characteristics of the new active ingredients after processing

the processing principle of BPRC was investigated by network pharmacology.

Result

A total of 19 ingredients in BPRC were identified

six of which were newly added cholic acids after processing. It was determined that the alkaloids

including worenine

epiberberine

jatrorrhizine

coptisine

berberrubine

berberine

palmatine and cholic acids

including glycohyodeoxycholic acid

taurohyodeoxycholic acid

glycochenodeoxycholic acid

hyodeoxycholic acid and taurochenodeoxycholic acid

were identified as material basis of BPRC

A total of 66 targets of reducing excess fire of liver and gallbladder of BPRC were screened. There were 16 common targets and multiple same signaling pathways between cholic acids and alkaloids of BPRC

and many lesions of excess fire of liver and gallbladder were target organs of cholic acids. By acting on some targets

including albumin (ALB)

Caspase-3 (CASP3)

mitogen-activated protein kinase 14 (MAPK14)

glucocorticoid receptor (NR3C1) and other targets and some signaling pathways

including interleukin (IL)-17

phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt)

MAPK and other pathways

BPRC could reduce excess fire of liver and gallbladder.

Conclusion

BPRC has the characteristics of multi-component

multi-target and multi-pathway on reducing excess fire of liver and gallbladder. Bile and Coptidis Rhizoma have synergistic effect and bile can enhance the intensity of BPRC in lesions

which confirms the processing theory that the effect of BPRC on excess fire of liver and gallbladder enhance after being processed by bile.

关键词

Keywords

references

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