Study on antidepressant mechanism of Chaigui Granules on urine metabolic marker of CUMS rats
Objective 1H-NMR dynamic metabonomics and integrated network pharmacology were used to explore the key pathways and potential targets of Chaigui Granules(CGG)in regulating the antidepressant effect of chronic unpredictable mild stress(CUMS)rats urinary metabolic markers.Methods Except the control group,CUMS model was made in all groups for 7 weeks,and only in the first 4 weeks,1 hour after ig administration for 3 weeks,the model was established and the drug intervention was carried out in venlafaxine(35 mg·kg-1)and CGG(8.3 g·kg-1),study the antidepressant effect of CGG through body weight,sugar water preference experiment,and forced swimming experiment.The urine was collected at different time points.1H-NMR metabonomics was used to monitor the dynamic changes of urinary metabolic markers during the administration of CGG,and to explore the key pathways and potential targets of CGG in the treatment of depression by integrated biological network analysis.Results Compared with the model group,CGG significantly increased the body weight of rats(P＜0.05),significantly increased the sugar water preference rate(P＜0.01),and significantly reduced the swimming immobility time(P＜0.05,0.01).The results showed that CGG could dynamically modulate 10 urinary metabolic markers such as Aspartate to near normal levels,and the administration cycle of different metabolites to normal levels was different.The levels of pantothenate and hippurate were significantly reduced one week after CGG administration(P＜0.05,0.01).Methionine,methylamine and aspartate were significantly reduced two weeks after CGG administration(P＜0.01),2-oxoglutarate,taurine,butyrate,lysine and lactic acid were significantly reduced after three weeks of CGG administration(P＜0.05、0.01).At the same time,the results of network pharmacology analysis indicated that CGG might exert its therapeutic effect by adjusting the key pathway of alanine,aspartate and glutamate metabolism,the four targets of GPT,GLUD1,GLUD2 and GOT2 in the metabolic pathway may be potential targets of CGG in the treatment of depression.Conclusion This study explored the mechanism of CGG in the treatment of depression from 1H-NMR dynamic metabolomics and biological network analysis,and provided a scientific theoretical basis for the clinical application of CGG.
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