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Study on urine metabolome of platycodon grandiflorus leaves extracts on depression in mice based on UPLC-QTOF-MS technology
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DOI   10.11656/j.issn.1672-1519.2020.01.23
Key Words   platycodon grandiflorum leaves;depression;metabolomics;metabolic pathway
Author NameAffiliation
CAI Xiaojun Heilongjiang Academy of Chinese Medicine, Harbin 150036, China 
XIE Yanpeng Heilongjiang Academy of Chinese Medicine, Harbin 150036, China 
HU Yang Heilongjiang Academy of Chinese Medicine, Harbin 150036, China 
LIU Song Heilongjiang Academy of Chinese Medicine, Harbin 150036, China 
WANG Lei Heilongjiang Academy of Chinese Medicine, Harbin 150036, China 
Abstract
    [Objective] To investigate the effect of platycodon grandiflorum leaves extract on depression model in mice based on UPLC-QTOF-MS technology,and to explore the pathogenesis of depression in mice and the mechanism of platycodon grandiflorum leaves intervention.[Methods] The depression model of mice was induced by intraperitoneal injection of lipopolysaccharide (1 mg/kg). The mice were randomly divided into model group and drug group according to their body weight. Eight healthy mice of the same batch were selected as the control group. The mice in the administration group were treated with platycodon grandiflorum leaves by gavage[400 mg/(kg·d)] for one week. The control group and the model group were treated with physiological saline of equal volume. IL-6 and TNF-α were used for evaluation,and urine metabolomics was used for data acquisition and data processing. By tracing the key metabolic enzymes and pathways upstream through terminal metabolites to evaluated comprehensively from the overall metabolic level the pharmacodynamics and mechanism of platycodon grandiflorum leaves.[Results] The results of biochemical indexes showed that the expressions of IL-6 and TNF-α in the prefrontal cortex of the model group were significantly higher than those in the control group(P<0.01);compared with the model group,the indexes in the drug group showed a significant retrograde trend(P<0.05). The results of urine metabolomics study showed that the metabolic profiles of three groups of mice clustered significantly. Moreover,the metabolic distribution of the drug group was closer to that of the control group,which showed that the metabolic status of the drug group was closer to that of the healthy mice at the overall metabolic level. Progenesis QI software was used to identify 29 urine biomarkers which contributed significantly to grouping. It involves Linoleic acid metabolism,Arachidonic acid metabolism,Glutathione metabolism,Sphingolipid metabolism,Energy metabolism and so on. The above metabolic pathways showed a tendency to be reversed after platycodon grandiflorum leaves were given.[Conclusion] The extract of platycodon grandiflorum leaves has a certain therapeutic effect on depressive mice. The regulation of multi-component and multi-path pathway may be the key to its effectiveness. It can indirectly intervene depression by regulating Linoleic acid metabolism and Arachidonic acid metabolism.

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