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Metabolomics study of Buyang Huanwu Tang Decoction in ischemic stroke mice by 1H NMR

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Abstract

The characteristic of traditional Chinese medicine (TCM) is the use of multiple components for multiple therapeutic targets. Metabolomics provides a measurement of multiparametric metabolic response in a living system to the effects of genetic or environmental modulation, which has been highly favored in evidence-based TCM study in recent years. A Chinese herbal decoction of Buyang Huanwu Tang (BHTD) has long been used for stroke treatment. In this study, nuclear magnetic resonance (NMR)-based metabolomics was conducted to examine the therapeutic effects of BHTD in a cerebral artery occlusion-induced sub-acute stroke mouse model. The brain tissues were analyzed in a nano probe using Carr-Purcell-Meiboom-Gill (CPMG) sequence for metabolic profiles. The spectral data were analyzed in conjunction with orthogonal partial least-squares discriminant analysis (OPLS-DA) to discover the metabolic effects in stroke mice and the effects of BHTD treatment. Twenty endogenous metabolites were identified. Among them, significant increase in acetone, β-hydroxybutyrate, glucose, lactate, and alanine, and significant decrease of γ-aminobutyrate, acetate, N-acetyl aspartate, glutamate, citrate, creatine + phosphocreatine, choline, phosphocholine + glycerophosphocholine, taurine, myo-inositol, glycerol, glycolate, and adenine were found in the brain of stroke mice when compared with normal mice. OPLS-DA results showed that metabolite profiles in the brain of ischemic stroke mice, treated with BHTD, were partially reversed to normal. After BHTD treatment, the levels of most abnormal metabolites were restored. Our study suggests that NMR-based metabolomics can provide a simple and easy tool for herbal therapeutic evaluation.

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Abbreviations

GABA:

γ-Aminobutyrate

BHTD:

Buyang Huanwu Tang

CPMG:

Carr-Purcell-Meiboom-Gill

CI/R:

Cerebral ischemic/reperfusion

Cr:

Creatine

GPC:

Glycerophosphocholine

1H-MRS:

1H-magnetic resonance spectroscopy

β-HB:

β-hydroxybutyrate

NAA:

N-acetyl aspartate

OPLS-DA:

Orthogonal partial least-squares discriminant analysis

PLS-DA:

Partial least squares discriminant analysis

PC:

Phosphocholine

PCr:

Phosphocreatine

PCA:

Principal component analysis

1H NMR:

Proton nuclear magnetic resonance

TCM:

Traditional Chinese medicine

VIP:

Variable importance of projection

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Acknowledgments

We are indebted to Prof. Mark R. Viant (School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK) for his generous provision of ProMetab software. This work was financially supported by grants from the National Science Council (NSC 99-2628-B-077-001-MY3) and the National Research Institute of Chinese Medicine (NRICM 99 PP02 & 100 PP02).

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Authors and Affiliations

  1. National Research Institute of Chinese Medicine, Taipei, 112, Taiwan

    Hong-Jhang Chen, Yuh-Chiang Shen, Keng-Chang Tsai, Chung-Kuang Lu, Chien-Chang Shen & Yun-Lian Lin

  2. Institute of Environmental Health, National Taiwan University, Taipei, 100, Taiwan

    Chin-Yu Lin

  3. School of Pharmacy, National Taiwan University, Taipei, 100, Taiwan

    Yun-Lian Lin

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  1. Hong-Jhang Chen
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Correspondence to Chien-Chang Shen or Yun-Lian Lin.

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Hong-Jhang Chen and Yuh-Chiang Shen are contributed equally.

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Chen, HJ., Shen, YC., Lin, CY. et al. Metabolomics study of Buyang Huanwu Tang Decoction in ischemic stroke mice by 1H NMR. Metabolomics 8, 974–984 (2012). https://doi.org/10.1007/s11306-011-0394-0

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