Absolute quantitative analysis of endogenous neurotransmitters and amino acids by liquid chromatography-tandem mass spectrometry combined with multidimensional adsorption and collision energy defect

Shen, Jiajia; He, Wei; Li, Haofeng; Li, Changjian; Yan, Caixia; Yu, Tengjie; Guo, Huimin; Hu, Kangrui; Du, Yisha; Sun, Hong; Xie, Lin; Fang, Pingfei; Liang, Yan

doi:10.1016/j.chroma.2020.461867

Cited by 15 publications

(7 citation statements)

References 36 publications

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“…Rat plasma samples were processed according to previous report (Shen et al, 2021). A total of 500 μl of ice‐cold acetonitrile containing 200 ng of 2,5‐dihydroxybenzoic acid (DHB, internal standard) was added to the specimens.…”

Section: Methodsmentioning

confidence: 99%

Aberrant branched‐chain amino acid accumulation along the microbiota–gut–brain axis: Crucial targets affecting the occurrence and treatment of ischaemic stroke

Shen

Guo

Liu

et al. 2022

British J Pharmacology

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Background and Purpose Although increasing evidence illustrated that the bidirectional communication between the brain and the gut is closely related to the occurrence of various complex diseases. Limited effort has been made to explore the influence of intestinal flora on the risk of ischaemic stroke. The present study aims to identify microbiota and specialized microbiota metabolites related to the occurrence and treatment of ischaemic stroke. Experimental Approach The role of microbiota in the occurrence and the treatment of ischaemic stroke was evaluated on ischaemia/reperfusion (I/R), pseudo‐germ‐free and faecal transplantation animals. The target microbiota and specialized metabolites were identified by comparing their distribution in flora and metabolomic profiles in ischaemic stroke patients and animals with compared with healthy controls. The effects and mechanisms involved of the targeted metabolites in ischaemic stroke were explored in ischaemia/reperfusion rats, hypoxia/reoxygenation PC12 cells and LPS‐induced inflammatory BV2 cells. Key Results Both ischaemic stroke patients and I/R rats had significant accumulation of branched‐chain amino acids, which were closely associated with gut microflora dysbiosis and the development of ischaemic stroke. Lactobacillus helveticus (L.hel) and Lactobacillus brevis (L.bre) are identified as the microbiota most affected by ischaemia/reperfusion modelling and treatment. L.hel and L.bre colonization exhibited significant neuroprotective activity and could greatly alleviate the accumulation of branched‐chain amino acids. In addition, branched‐chain amino acid (BCAA) accumulation was shown to exacerbate microglia‐induced neuroinflammation by activating AKT/STAT3/NF‐κB signalling. Conclusion and Implications Our findings demonstrated the crucial role of intestinal flora and microbiota metabolites in the occurrence and treatment of ischaemic stroke.

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Section: Methodsmentioning

confidence: 99%

Aberrant branched‐chain amino acid accumulation along the microbiota–gut–brain axis: Crucial targets affecting the occurrence and treatment of ischaemic stroke

Shen

Guo

Liu

et al. 2022

British J Pharmacology

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“…Our previous study has established a LC-MS/MS method for the quantitative analysis of amino acids in biological matrix ( Shen et al, 2021 ). Ascorbic acid (20 mM) was added to 30 mg of the rat striatum.…”

Section: Methodsmentioning

confidence: 99%

Feasibility exploration of GSH in the treatment of acute hepatic encephalopathy from the aspects of pharmacokinetics, pharmacodynamics, and mechanism

Hu,

Xu,

Fan

et al. 2024

Front. Pharmacol.

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Our previous study highlighted the therapeutic potential of glutathione (GSH), an intracellular thiol tripeptide ubiquitous in mammalian tissues, in mitigating hepatic and cerebral damage. Building on this premise, we posited the hypothesis that GSH could be a promising candidate for treating acute hepatic encephalopathy (AHE). To verify this conjecture, we systematically investigated the feasibility of GSH as a therapeutic agent for AHE through comprehensive pharmacokinetic, pharmacodynamic, and mechanistic studies using a thioacetamide-induced AHE rat model. Our pharmacodynamic data demonstrated that oral GSH could significantly improve behavioral scores and reduce hepatic damage of AHE rats by regulating intrahepatic ALT, AST, inflammatory factors, and homeostasis of amino acids. Additionally, oral GSH demonstrated neuroprotective effects by alleviating the accumulation of intracerebral glutamine, down-regulating glutamine synthetase, and reducing taurine exposure. Pharmacokinetic studies suggested that AHE modeling led to significant decrease in hepatic and cerebral exposure of GSH and cysteine. However, oral GSH greatly enhanced the intrahepatic and intracortical GSH and CYS in AHE rats. Given the pivotal roles of CYS and GSH in maintaining redox homeostasis, we investigated the interplay between oxidative stress and pathogenesis/treatment of AHE. Our data revealed that GSH administration significantly relieved oxidative stress levels caused by AHE modeling via down-regulating the expression of NADPH oxidase 4 (NOX4) and NF-κB P65. Importantly, our findings further suggested that GSH administration significantly regulated the excessive endoplasmic reticulum (ER) stress caused by AHE modeling through the iNOS/ATF4/Ddit3 pathway. In summary, our study uncovered that exogenous GSH could stabilize intracerebral GSH and CYS levels to act on brain oxidative and ER stress, which have great significance for revealing the therapeutic effect of GSH on AHE and promoting its further development and clinical application.

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“…LC-MS/MS method was developed to determine neurotransmitters in different brain regions, serum, and plasma. Experimental conditions refer to the literature ( Shen et al, 2021 ). The mobile phase consisted of solvent A (0.2% formic acid and 5.0 mM ammonium formate in water) and solvent B (acetonitrile).…”

Section: Methodsmentioning

confidence: 99%

Isoliquiritigenin Alleviates Semen Strychni-Induced Neurotoxicity by Restoring the Metabolic Pathway of Neurotransmitters in Rats

et al. 2021

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Acute neurotoxicity of Semen Strychni can result in sudden death in epilepsy. The detoxification method and mechanism of Semen Strychni acute poisoning have not been clarified. This experiment focused on the mechanism of Semen Strychni neurotoxicity and the alleviation effects of isoliquiritigenin. The rats were intraperitoneally injected with Semen Strychni extract (125 mg/kg), followed by oral administration of isoliquiritigenin (50 mg/kg) for 7 days. FJ-B staining was used to evaluate the degree of injury on hippocampus neurons. The concentration of monoamines, amino acids, and choline neurotransmitters, the Dopamine (DA) and 5-hydroxytryptamine (5-HT) metabolic pathway in the hippocampus, cerebellum, striatum, prefrontal cortex, hypothalamus, serum, and plasma were detected by LC-MS/MS. The expression of neurotransmitter metabolic enzymes [catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO)] and neurotransmitter receptors [glutamate N-methyl-D-aspartic acid receptors (NMDARs) and gamma-aminobutyric acid type A receptor (GABRs)] were, respectively determined using ELISA and qRT-PCR. The results indicated that Semen Strychni induced neuronal degeneration in the hippocampal CA1 region. Meanwhile, Semen Strychni inhibited the mRNA expression of NMDAR1, NMDAR2A, NMDAR2B, GABRa1, GABRb2 and reduced the level of MAO, which disrupted the DA and 5-HT metabolic pathway. However, isoliquiritigenin reversed these effects. In summary, isoliquiritigenin showed alleviation effects on Semen Strychni-induced neurotoxicity, which could be attributed to restoring neurotransmitters metabolic pathway, most likely through the activation of NMDA receptors.

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Absolute quantitative analysis of endogenous neurotransmitters and amino acids by liquid chromatography-tandem mass spectrometry combined with multidimensional adsorption and collision energy defect

Cited by 15 publications

References 36 publications

Aberrant branched‐chain amino acid accumulation along the microbiota–gut–brain axis: Crucial targets affecting the occurrence and treatment of ischaemic stroke

Aberrant branched‐chain amino acid accumulation along the microbiota–gut–brain axis: Crucial targets affecting the occurrence and treatment of ischaemic stroke

Feasibility exploration of GSH in the treatment of acute hepatic encephalopathy from the aspects of pharmacokinetics, pharmacodynamics, and mechanism

Isoliquiritigenin Alleviates Semen Strychni-Induced Neurotoxicity by Restoring the Metabolic Pathway of Neurotransmitters in Rats

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