UPLC-ESI-IT-TOF-MS metabolomic study of the therapeutic effect of Xuefu Zhuyu decoction on rats with traumatic brain injury

Fu, Chunyan; Wu, Qian; Zhang, Zhimin; Xia, Zian; Ji, Hongchao; Lü, Hongmei; Wang, Yang

doi:10.1016/j.jep.2019.112149

Cited by 26 publications

(17 citation statements)

References 41 publications

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“…Evaluating the mechanism of pharmacological action of traditional Chinese medicine (TCM) is difficult because of the unclear active components and their possible synergistic actions (Yang et al, 2015). Metabolomics can comprehensively profile the metabolites in the entire organism that alter in responses to the pathophysiological or drug stimuli, identify their related metabolic pathways, and systematically clarify the mechanism of drug actions (Newgard, 2017;Fu et al, 2019). Thus metabolomics may be a powerful approach to unveil the underlying mechanism of MHD.…”

Section: Introductionmentioning

confidence: 99%

“…Thus metabolomics may be a powerful approach to unveil the underlying mechanism of MHD. Recently, ultrahigh performance liquid chromatography (UPLC) coupled with a high resolution mass spectrometer (MS) such as Q-Exactive Orbitrap MS are drawing great attention in metabolomics because of the superior peak resolution, selectivity, sensitivity, reproducibility and analysis speed (Fu et al, 2019;Zhong et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism

et al. 2021

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Acute liver failure (ALF) is a serious clinical disorder with high fatality rates. Mahuang decoction (MHD), a well-known traditional Chinese medicine, has multiple pharmacological effects, such as anti-inflammation, anti-allergy, anti-asthma, and anti-hyperglycemia. In this study, we investigated the protective effect of MHD against ALF. In the lipopolysaccharide and D-galactosamine (LPS/D-GalN)-induced ALF mouse model, the elevated activities of the serum alanine and aspartate transaminases as well as the liver pathological damage were markedly alleviated by MHD. Subsequently, a metabolomics study based on the ultrahigh performance liquid chromatograph coupled with Q Exactive Orbitrap mass spectrometry was carried to clarify the therapeutic mechanisms of MHD against ALF. A total of 36 metabolites contributing to LPS/D-GalN-induced ALF were identified in the serum samples, among which the abnormalities of 27 metabolites were ameliorated by MHD. The analysis of metabolic pathways revealed that the therapeutic effects of MHD are likely due to the modulation of the metabolic disorders of tricarboxylic acid (TCA) cycle, retinol metabolism, tryptophan metabolism, arginine and proline metabolism, nicotinate and nicotinamide metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan synthesis, as well as cysteine and methionine metabolism. This study demonstrated for the first time that MHD exerted an obvious protective effect against ALF mainly through the regulation of TCA cycle and amino acid metabolism, highlighting the importance of metabolomics to investigate the drug-targeted metabolic pathways.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism

et al. 2021

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“…Biofluids are commonly analyzed in metabolomics to reflect systemic metabolic perturbations (Beckonert et al, 2007). Our recent reports of plasma metabolomics indicated that XFZYD exerts neuroprotective effects on the controlled cortical impact (CCI) rats model via multiple pathways (Feng et al, 2017;Fu et al, 2019). However, due to the blood-brain barrier, the metabolic alterations in the biofluid may not be in parallel with that in the injured brain (Qian et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Metabolomics Deciphers Potential Targets of Xuefu Zhuyu Decoction Against Traumatic Brain Injury in Rat

et al. 2020

Front. Pharmacol.

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Xuefu Zhuyu decoction (XFZYD) performs multiple functions for traumatic brain injury (TBI) treatment. However, its clinical application is limited by the incomplete exploration of targets and inadequate discussion of mechanisms. We aimed to investigate the metabolic alterations of XFZYD in acute and chronic stages of TBI. Sprague-Dawley rats were randomly divided into the sham, controlled cortical impact (CCI) and XFZYD group. Behavioral and histopathological tests were used to evaluate the neuroprotective effects. Coagulation assays were performed to assess safety. Moreover, we analyzed the metabolomic profiling of hippocampal samples with different time intervals after CCI by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Differential metabolites were screened by multivariate data analysis. To further uncover the association between candidate metabolites and biological interaction networks, we applied bioinformatics analysis using MetaboAnalyst 4.0, STITCH 5.0 and TCMSP. The potential mechanism was verified by ELISA and Western blot. XFZYD ameliorated neurological deficiencies post-CCI without impairing blood coagulation in the rat's model. Seventeen and fourteen metabolites were filtered on d 3 and 21, respectively. Eleven of potential metabolites were common at these time points, involving two significant pathways (arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis). Gamma-aminobutyric acid (GABA) and the related pathways were specifically affected by XFZYD at the acute phase of TBI, while biosynthesis of amino acids was the major pathway influenced at the chronic phase. This study provides broad insights into the therapeutic effects of XFZYD in treating TBI through the whole phases.

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“…Thereby, it is urgent to develop novel therapeutic strategies and drugs for the management of TBI. The traditional Chinese medicine, Xuefu Zhuyu Decoction (XFZYD), can invigorate the circulation of blood without any consumption of blood as well as dissipate blood stasis and promote angiogenesis [5,12] . Oral administration leads to peripheral vasodilation and enhanced aerobic catabolism, alleviating tissue edema, exudation, and inflammatory reaction by which clinical symptoms can be improved [5,13,14] .…”

Section: Introductionmentioning

confidence: 99%

Systematic Analysis of tRNA-Derived Small RNAs Reveals Effects of Xuefu-Zhuyu Decoction on Hippocampus of Rats after Traumatic Brain Injury

Dai¹,

Tang²,

Lu³

et al. 2021

Preprint

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Background: Traumatic brain injury (TBI) is one of the most common neurosurgical diseases which refers to brain function impairment or brain pathological changes induced by external causes. A traditional Chinese medicine, Xuefu Zhuyu Decoction (XFZYD), has been indicated to harbor therapeutic property against TBI. Transfer RNA (tRNA)-derived small RNAs i.e., tsRNAs (a group of small RNAs derived from tRNAs) are multifunctional regulatory non-coding RNAs generated under pressure and implicated in the progression of TBI.Methods: TBI model was successfully constructed by using of rats. Further using sequencing and omics to identify novel tsRNAs as drug targets for XFZYD therapy against TBI in rat hippocampus. qPCR assay was used to further verify the experimental results. GO analyzed the signaling pathways of downstream target genes of tsRNA in XFZYD regulated TBI model. qPCR was used to detect the influence of over-expressed tsRNA mimic/inhibitor on their target genes in PC12 cell.Results: Our RNA-Seq data illustrates that 11 tsRNAs were mediated by the XFZYD. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment and nicotine pharmacodynamics pathway. We also confirm that Pi4kb, Mlh3, Pcdh9, and Ppp1cb were targets genes of 2 XFZYD regulated tsRNAs in hippocampus of rat model and PC12 cells. Furthermore, biological function analysis revealing potential therapeutic effects of tsRNAs, and results found Mapk1, Gnai1 was the related genes of for XFZYD therapy against TBI.Conclusion: Our work successfully illuminates the efficiency of XFZYD for the treatment of TBI. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment and nicotine pharmacodynamics pathway in TBI rat model.

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UPLC-ESI-IT-TOF-MS metabolomic study of the therapeutic effect of Xuefu Zhuyu decoction on rats with traumatic brain injury

Cited by 26 publications

References 41 publications

Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism

Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism

Metabolomics Deciphers Potential Targets of Xuefu Zhuyu Decoction Against Traumatic Brain Injury in Rat

Systematic Analysis of tRNA-Derived Small RNAs Reveals Effects of Xuefu-Zhuyu Decoction on Hippocampus of Rats after Traumatic Brain Injury

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