Integrated plasma and urine metabolomics coupled with HPLC/QTOF-MS and chemometric analysis on potential biomarkers in liver injury and hepatoprotective effects of Er-Zhi-Wan

被引：73

作者：

Yao, Weifeng ^{[1
,2
]}

Gu, Haiwei ^{[2
,5
]}

Zhu, Jiangjiang ^{[2
]}

Barding, Gregory ^{[2
,6
]}

Cheng, Haibo ^{[3
]}

Bao, Beihua ^{[1
,4
]}

Zhang, Li ^{[1
,4
]}

Ding, Anwei ^{[1
,4
]}

Li, Wei ^{[1
]}

机构：

[1] Nanjing Univ Chinese Med, Coll Pharm, Nanjing 210023, Jiangsu, Peoples R China

[2] Univ Washington, Dept Anesthesiol & Pain Med, Northwest Metabol Res Ctr, Seattle, WA 98109 USA

[3] Nanjing Univ Chinese Med, Jiangsu Engn Lab Res & Industrializat Empir Formu, Nanjing 210023, Jiangsu, Peoples R China

[4] Nanjing Univ Chinese Med, Jiangsu Key Lab Tradit Chinese Med Formulae Res, Nanjing 210023, Jiangsu, Peoples R China

[5] E China Inst Technol, Jiangxi Key Lab Mass Spectrometry & Instrumentat, Nanchang, Jiangxi, Peoples R China

[6] Calif State Polytech Univ Pomona, Dept Chem & Biochem, Pomona, CA 91768 USA

来源：

ANALYTICAL AND BIOANALYTICAL CHEMISTRY | 2014年 / 406卷 / 28期

基金：

中国国家自然科学基金;

关键词：

Integrated metabolomics; Er-Zhi-Wan (EZW); Hepatoprotective; HPLC/QTOF-MS; Chemometrics; TRADITIONAL CHINESE MEDICINE; PIPECOLIC ACID; ERZHI PILL; MASS; MODEL; RATS; METABONOMICS; BIOCHEMISTRY; PROTEOME; SYSTEMS;

D O I：

10.1007/s00216-014-8169-x

中图分类号：

Q5 [生物化学];

学科分类号：

070307 [化学生物学];

摘要：

Metabolomics techniques are the comprehensive assessment of endogenous metabolites in a biological system and may provide additional insight into the molecular mechanisms. Er-Zhi-Wan (EZW) is a traditional Chinese medicine formula, which contains Fructus Ligustri Lucidi (FLL) and Herba Ecliptae (HE). EZW is widely used to prevent and treat various liver injuries through the nourishment of the liver. However, the precise molecular mechanism of hepatoprotective effects has not been comprehensively explored. Here, an integrated metabolomics strategy was designed to assess the effects and possible mechanisms of EZW against carbon tetrachloride-induced liver injury, a commonly used model of both acute and chronic liver intoxication. High-performance chromatography/quadrupole time-of-flight mass spectrometry (HPLC/QTOF-MS) combined with chemometric approaches including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to discover differentiating metabolites in metabolomics data of rat plasma and urine. Results indicate six differentiating metabolites, tryptophan, sphinganine, tetrahydrocorticosterone, pipecolic acid, l-2-amino-3-oxobutanoic acid and phosphoribosyl pyrophosphate, in the positive mode. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan metabolism, sphingolipid metabolism, steroid hormone biosynthesis, lysine degradation, glycine, serine and threonine metabolism, and pentose phosphate pathway. Of note, EZW has a potential pharmacological effect, which might be through regulating multiple perturbed pathways to the normal state. Our findings also showed that the robust integrated metabolomics techniques are promising for identifying more biomarkers and pathways and helping to clarify the function mechanisms of traditional Chinese medicine.

引用

页码：7367 / 7378

页数：12

共 53 条

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