Metabolomics reveals the effect of Xuefu Zhuyu Decoction on plasma metabolism in rats with acute traumatic brain injury.

Dandan Feng,Tao Tang,Pingping Gan,Feng He,Zian Xia,Rong Fan,Wei Huang,Chunhu Zhang,Jing Zhou,Weijun Peng,Hanjin Cui,Yang Wang,Xingui Xiong,Zhiming Wang,Hongmei Lu

doi:10.18632/oncotarget.21876

Abstract

Xuefu Zhuyu Decoction (XFZY), an important traditional Chinese herbal formula, has been reported effective on traumatic brain injury (TBI) in rats. However, its cerebral protection mechanism has not been clarified at the metabolic level. This work aims to explore the global metabolic characteristics of XFZY in rats during the acute phase of TBI on days 1 and 3. A plasma metabolomics method based on gas chromatography-mass spectrometry coupled with univariate analysis and multivariate statistical analysis was performed in three groups (Sham, Vehicle, XFZY). Then, a pathway analysis using MetaboAnalyst 3.0 was performed to illustrate the pathways of therapeutic action of XFZY in TBI. XFZY treatment attenuates neurological dysfunction and cortical lesion volume post-injury on day 3, and reverses the plasma metabolite abnormalities (glutamic acid, lactic acid, 3-hydroxybutyric acid, and ribitol, etc.). These differential metabolites are mainly involved in D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and inositol phosphate metabolism. Our study reveals potential biomarkers and metabolic networks of acute TBI and neuroprotection effects of XFZY, and shows this metabolomics approach with MetaboAnalyst would be a feasible way to systematically study therapeutic effects of XFZY on TBI.

Highlights

Traumatic brain injury (TBI) is the major cause of death and disability in individuals under the age of 45 years [1, 2]
A plasma metabolomics method based on gas chromatography-mass spectrometry coupled with univariate analysis and multivariate statistical analysis was performed in three groups (Sham, Vehicle, Xuefu Zhuyu Decoction (XFZY))
Our findings showed that metabolic changes of XFZY treatment on cortical impact injury (CCI) are predominantly related to abnormal amino acid metabolism

Summary

Introduction

Traumatic brain injury (TBI) is the major cause of death and disability in individuals under the age of 45 years [1, 2]. It is frequently referred to as the “silent epidemic” because of undetected complications that resulted from TBI and limited awareness, funding, and research progress [4, 5]. In the United State, an estimated 1.7 million people suffer from TBI annually [6], and about 5.3 million people live with a TBI-related disability [7]. Despite progress made in diagnosis, neurological care, and functional rehabilitation, no effective therapy is currently available for TBI [8]. Since TBI is not a single www.impactjournals.com/oncotarget

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