Effects Of Chaihu Shu Gan San On The Prefrontal Cortex Metabolomics In Depressive Model Rats

Objective: To explore the mechanism of Chaihu Shu Gan San antidepressant effect,metabolomics was used to search for differential metabolites and metabolic pathways in the Prefrontal cortex(PFC)related to Chaihu Shu Gan San antidepressant activity in rats.Methods:(1)Healthy adult male rats were randomly divided into four groups: Sham group(Sham),Model group(Model),Chaihu Shu Gan San group(CSGS)and Flouxetine group.Rats except Sham group were exposed by random discontinuous CUMS methods every day.Forced swimming test and sugar preference test of rats in each group were measured and body weight of rats was recorded at day 0,14 and 28.(2)Metabolomics method was used to detect PFC tissues in each group and screen differential metabolites.(3)Quantitative detection of differential metabolites under CSGS intervention by ELISA.(4)Metabo Analyst enriched metabolic pathways to uncover potential biological significance.Results:(1)on day 0,there were no significant differences in body weight and behavioral indexes among each group.On day 14 and 28,compared with Sham group,rats in Model group had slower body weight gain,lower sugar preference rate,and longer resting time in forced swimming test(P<0.05).On day 14,the sugar preference rate of CSGS group and Flouxetine group was increased compared with Model group(P<0.05).On day 28,compared with Model group,CSGS group and Flouxetine group had faster body weight gain,higher sugar water preference rate and shorter immobility time in forced swimming test(P<0.05).(2)Orthogonal partial least squares analysis could significantly distinguish the metabolic profile between Sham group and Model group,Model group and CSGS group,respectively.(3)Compared with Sham group,10 metabolites such as histidine of Model group were significantly changed.The concentration of acetylcholine decreased significantly after CSGS intervention,and the ELISA verified the change of acetylcholine metabolomics.(4)Pathway analysis revealed that pathways such as histidine metabolism are strongly associated with depression.Conclusion: Chaihu Shu Gan San has a certain effect on depression rats.This study provides an new experimental basis for the antidepressant effect of Chaihu Shu Gan San with metabonomics.