Available online 13 October 2022

The mechanism of theanine in prevention of depression based on metabolomics was studied for the first time.

Simultaneous untargeted and targeted metabolomics studies in CUMS-induced rat periphery and central nervous system were carried out for the first time.

A rapid HILIC-QQQ-MS/MS method was developed and validated for the accurate determination of altered amino acids and neurotransmitters.

L-theanine has been shown to have a therapeutic effect on depression. However, whether L-theanine has an excellent preventive effect on depression in children and adolescents and its mechanism have not been well explained. Given the complexity of the pathogenesis of depression, this study investigated the preventive effect and mechanism of L-theanine on depression in juvenile rats by combining serum and hippocampal metabolomic strategies. Behavioral tests, hippocampal tissue sections, and serum and hippocampal biochemical indexes were studied, and the results confirmed the preventive effect of L-theanine. Untargeted reversed-phase liquid chromatography–quadrupole-time-of-flight mass spectrometry and targeted hydrophilic interaction liquid chromatography-triple quadrupole mass spectrometry were developed to analyze the metabolism changes in serum and hippocampus to screen for potential biomarkers related to L-theanine treatment. The results suggested that 28 abnormal metabolites in the serum and hippocampus that were considered as potential biomarkers returned to near-normal levels after L-theanine administration. These biomarkers were involved in various metabolic pathways, mainly including amino acid metabolism and lipid metabolism. The levels of amino acids and neurotransmitters in the phenylalanine, tryptophan and glutamate pathways were significantly reduced after L-theanine administration compared with chronic unpredictable mild stress-induced rats. In summary, L-theanine had a significant preventive effect on depression and achieved its preventive results on depression by regulating various aspects of the body, such as amino acids, lipids, and inflammation. This research systematically analyzed the mechanism of L-theanine in preventing depression and laid the foundation for applying L-theanine to prevent depression in children and adolescents.

L-theanine

Depression

Metabolomics

Liquid chromatography-mass spectrometry

© 2022 The Author(s). Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.