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

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.