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Metabolomics Coupled with Pattern Recognition and Pathway Analysis on Potential Biomarkers in Liver Injury and Hepatoprotective Effects of Yinchenhao

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Abstract

Metabolomics can provide an opportunity to develop the systematic analysis of the metabolites in biological samples and has been increasingly applied to discovering and identifying biomarkers and perturbed pathways. It enables us to better understand the metabolic pathways which can clarify the mechanism of traditional Chinese medicines (TCM). Yinchenhao (YCH, Artemisia annua L), a famous TCM plant, has been used clinically for more than a thousand years to relieve liver diseases in Asia, and its mechanisms are not still completely clear. Here, metabolomic techniques may provide additional insight, and our investigation was designed to assess the effects and possible mechanisms of YCH on α-naphthylisothiocyanate (ANIT)-induced liver injury. Metabolite profiling was performed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) combined with pathway analysis and pattern recognition approaches including independent component analysis (ICA) and partial least squares-discriminant analysis (PLS-DA). Biochemistry test was also performed for the liver tissue and plasma samples. The changes in metabolic profiling were restored to their baseline values after YCH treatment according to the ICA score plots. Of note, YCH has a potential pharmacological effect through regulating multiple perturbed pathways to normal state, correlating well to the assessment of biochemistry test. Five different potential biomarkers in the positive mode contributing to the treatment of YCH were discovered. Pathway analysis showed that these metabolites were associated with perturbations in pyrimidine metabolism, primary bile acid biosynthesis, and propanoate metabolism, which may be helpful to further understand the action mechanisms of YCH. It showed that changed biomarkers and pathways may provide evidence to insight into drug action mechanisms and drug discovery.

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Acknowledgments

This work was supported by grants from the Key Program of Natural Science Foundation of State (Grant Nos. 90709019, 81173500, 81373930, 81302905, 81102556, and 81202639), National Key Technology Research and Development Program of the Ministry of Science and Technology of China (Grant Nos. 2011BAI03B03, 2011BAI03B06, and 2011BAI03B08), and National Key Subject of Drug Innovation (Grant No. 2009ZX09502-005).

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The authors declare no competing financial interests.

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Authors and Affiliations

  1. National TCM Key Laboratory of Serum Pharmacochemistry, Key Laboratory of Metabolomics and Chinmedomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, 150040, Harbin, China

    Hui Sun, Ai-hua Zhang, Di-xing Zou, Wen-jun Sun, Xiu-hong Wu & Xi-jun Wang

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  1. Hui Sun
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  2. Ai-hua Zhang
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  3. Di-xing Zou
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  4. Wen-jun Sun
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Correspondence to Hui Sun or Xi-jun Wang.

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Sun, H., Zhang, Ah., Zou, Dx. et al. Metabolomics Coupled with Pattern Recognition and Pathway Analysis on Potential Biomarkers in Liver Injury and Hepatoprotective Effects of Yinchenhao. Appl Biochem Biotechnol 173, 857–869 (2014). https://doi.org/10.1007/s12010-014-0903-5

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  • DOI: https://doi.org/10.1007/s12010-014-0903-5

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