Main ways and target prediction of detoxification mechanism of <italic style="font-style: italic">Euphorbia kansui </italic>after stir-frying with vinegar

YANG Xiaoxu; HE Zhimin; LI Wenlan

doi:10.6039/j.issn.1001-0408.2023.04.08

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Main ways and target prediction of detoxification mechanism of Euphorbia kansui after stir-frying with vinegar

更新时间：2023-02-24

- Main ways and target prediction of detoxification mechanism of Euphorbia kansui after stir-frying with vinegar
- ZHONGGUO YAOFANG Vol. 34, Issue 4, Pages: 423-428(2023)
- 作者机构：
  
  哈尔滨商业大学药学院，哈尔滨　150001
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.04.08
  CLC： R917;R285
- Published：28 February 2023，
  
  Received：24 August 2022，
  
  Revised：02 January 2023，
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杨晓旭,贺志敏,李文兰.甘遂醋炙减毒机制的主要途径及靶点预测 ^Δ[J].中国药房,2023,34(04):423-428.

YANG Xiaoxu,HE Zhimin,LI Wenlan.Main ways and target prediction of detoxification mechanism of Euphorbia kansui after stir-frying with vinegar[J].ZHONGGUO YAOFANG,2023,34(04):423-428.
杨晓旭,贺志敏,李文兰.甘遂醋炙减毒机制的主要途径及靶点预测 ^Δ[J].中国药房,2023,34(04):423-428. DOI： 10.6039/j.issn.1001-0408.2023.04.08.

YANG Xiaoxu,HE Zhimin,LI Wenlan.Main ways and target prediction of detoxification mechanism of Euphorbia kansui after stir-frying with vinegar[J].ZHONGGUO YAOFANG,2023,34(04):423-428. DOI： 10.6039/j.issn.1001-0408.2023.04.08.

摘要

目的

研究甘遂醋炙减毒机制的主要途径及靶点。

方法

取24只SPF级SD大鼠，随机分为空白组、生甘遂组（850 mg/kg）、醋甘遂组（850 mg/kg），每组8只。空白组灌胃0.5%羧甲基纤维素钠溶液，生甘遂组、醋甘遂组给予相应的供试品药液，连续给药20 d，第20天收集大鼠12 h尿液。采用超高效液相色谱串联四极杆静电场轨道阱高分辨质谱（UPLC-Q-Exactive-MS）技术分析尿液样本。经Compound Discoverer 3.0软件进行数据前处理，经BioCyc、HMDB等数据库进行代谢物结构鉴定，应用主成分分析（PCA）、正交偏最小二乘法-判别分析（OPLS-DA）等多种方法观察不同组别是否呈现各自聚类现象；基于MetaboAnalyst进行通路分析，对甘遂醋炙减毒机制潜在靶点进行预测。

结果

鉴定出20个有显著性差异的内源性代谢物，其中有

-乙酰基-L-天冬氨酸、3-磷酸羟基丙酮酸等10个目标生物标志物为醋甘遂减毒机制作用靶点，参与的主要代谢通路包括精氨酸生物合成，丙氨酸、天冬氨酸和谷氨酸代谢，半胱氨酸和蛋氨酸代谢及精氨酸和D-鸟氨酸代谢。对通路中所有相关代谢物的生物学意义进行分析推测，甘遂醋炙后可能通过降低

-乙酰基-L-天冬氨酸水平缓解神经毒性，通过升高L-高精氨酸水平对心脑血管系统存在保护作用等。

结论

甘遂经醋炙后，可对机体的神经系统、心脑血管系统、免疫系统及能量代谢等方面的不利因素有明显改善，其发挥减毒机制的最集中相关的代谢通路为精氨酸生物合成。

Abstract

OBJECTIVE

To study main way and target of

Euphorbia kansui

after stir-frying with vinegar.

METHODS

Twenty-four SPF grade SD rats were randomly divided into blank group，

E. kansui

group （850 mg/kg） and vinegar

stir-fried

E. kansui

group （850 mg/kg）， with 8 rats in each group. Blank group was given 0.5% sodium carboxymethyl cellulose solution intragastrically， and

E. kansui

group and vinegar

stir-fried

E. kansui

group were given relevant test sample for consecutive 20 d. The rats’ urine of 12 hours was collected on the 20th day. The urine samples of rats in each group were determined by UPLC-Q-Exactive-MS. The data was pre-processed by Compound Discoverer 3.0 software， and the metabolite structure was identified by BioCyc， HMDB and other databases. Whether different groups presented their own clustering phenomenon was observed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）， etc. Based on the pathway analysis of MetaboAnalyst， the potential targets of detoxification mechanism of

E. kansui

after stir-frying with vinegar were predicted.

RESULTS

Twenty significantly differential endogenous metabolites were identified， of which 10 target metabolites， such as

-acetyl-L-aspartate and 3-phosphonooxypyruvic acid， were targets of detoxification mechanism of

E. kansui

after stir-frying with vinegar. The main metabolic pathways included arginine biosynthesis， alanine， aspartic acid and glutamic acid metabolism， cysteine and methionine metabolism， and arginine and D-ornithine metabolism. The biological significance of all related metabolites in the pathways was analyzed and speculated； after stir-frying with vinegar，

E. kansui

may alleviate neurotoxicity by reducing the level of

-acetyl-L-aspartic acid；

E. kansui

had a protective effect on cardio-cerebrovascular system by increasing the level of L-high arginine.

CONCLUSIONS

After stir-frying with vinegar，

E. kansui

can significantly improve the adverse factors in terms of nervous system， cardio-cerebrovascular system， immune system and energy metabolism. The most concentrated metabolic pathway related to its detoxification mechanism is arginine biosynthesis.

关键词

甘遂炮制减毒代谢组学目标生物标志物代谢通路

Keywords

processing and detoxificationmetabonomicstarget biomarkersmetabolic pathway

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Institute of Traditional Chinese Medicine/Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine/Key Laboratory of Glucolipid Metabolism Disease/Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Metabolic Diseases of Guangdong Province， Guangdong Pharmaceutical University

College of Traditional Chinese Medicine， Guangdong Pharmaceutical University

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Main ways and target prediction of detoxification mechanism of Euphorbia kansui after stir-frying with vinegar

DOI：10.6039/j.issn.1001-0408.2023.04.08

摘要

Abstract

关键词

Keywords

references