UPLC-Q-TOF-MS profiling of the hippocampus reveals metabolite biomarkers for the impact of Dl-3-n-butylphthalide on the lipopolysaccharideinduced rat model of depression

Abstract

Purpose: An increasing body of evidence reveals that inflammation is involved in the pathological mechanisms of depression. Our previous basic research confirmed that Dl-3-n-butylphthalide (NBP) possess anti-inflammatory properties. However, studies investigatingmetabolite biomarkers for the involvement of NBP in hippocampus tissue in the lipopolysaccharide (LPS)-induced rat model of depression are currently limited. Thus, the aim of this study was to identify metabolite biomarkers in the hippocampus for the impact of NBP in this model of depression. Material and methods: Male Sprague-Dawley rats were randomly allocated to one of the following three groups (n=6): Control, LPS-induced rat model of depression (LPS), and NBP involvement in the LPS-induced rat model of depression (LPS+NBP). Ultra-high-performance liquid chromatography-mass spectroscopy was used to determine the hippocampal metabolites. Multivariate statistical analysis was performed to identify differentially expressed hippocampal metabolites in the three groups. Results: Most of the identified differentially expressed metabolites were related to amino acid, lipid, energy, and oxidative stress metabolism. Additionally, metabolites were eventually connected to different pathways and metabolic networks, which may partly account for the pathophysiological process of depression. Conclusion: The present findings provide insight into the anti-inflammatory effects of NBP, and further elucidate the pathophysiologicalmechanisms underlying inflammation-induced depression.