Antidepressant Effects Of Coumaroylspermidine Extract From Safflower Injection Dregs

Safflower injection is a commonly used drug for cardiovascular diseases in clinical practice,with clear efficacy,and is a key Chinese medicine variety in Shanxi Province.A large amount of drug residues is yielded during the production process due to a water extraction and alcohol precipitation process.In the previous study,a coumaroylspermidine extract(CSE)was prepared with a total coumaroylspermidine content of more than 50% from safflower drug residues,and CSE showed antidepressant effect in tail suspension test and forced swimming test.However,the antidepressant effect and mechanisms of CSE is still unknown.Therefore,the antidepressant effect of CSE and its mechanisms were further investigated by chronic unpredictable mild stress(CUMS)rats.The main research contents are as follows:1.The study on antidepressant effect of CSE was evaluated by CUMS depression model.The results showed that the high-dose and middle-dose groups of CSE(34.60 mg/kg,17.30 mg/kg)significantly improved the sucrose preference of CUMS depression-like rats(P < 0.01);the middle-dose group(17.30 mg/kg)of CSE can increase significantly the crossing number and off grid time in the open field test(P < 0.05,P < 0.01),reduced significantly the off grid time(P < 0.05);the middle-dose group(8.65 mg/kg)of CSE can reduce significantly the immobility time of FST in CUMS rats(P < 0.05).The results show that CSE has a significant antidepressant effect with relieving the depression-like behavior.2.The antidepressant mechanisms of CSE was analyzed by monoamine neurotransmitters and HPA axis.There was detected the changes of monoamine neurotransmitter on hippocampus by UHPLC-MS/MS,CSE high-dose and meddle-dose groups(34.6 mg/kg,17.3 mg/kg)can increase significantly the content of 5-HT and NE metabolic pathways(P < 0.05,P < 0.01);It was detected the HPA-axis related hormones(ACTH,CRH,CORT)by enzyme-linked immunoblotting(ELISA).The results show that CSE high-dose,middle-dose and low-dose groups(34.6 mg/kg,17.3 mg/kg,8.65 mg/kg)can reverse significantly the abnormal hormone content caused by CUMS modeling(P < 0.01).3.The effect of CSE on serum metabolites in CUMS rats was studied by 1H-NMR metabolomics.PCA and OPLS-DA methods were used to find that the model group and the control group could be clearly separated,which indicates that the CUMS modeling is credible.Furthermore,10 differential metabolites related to depression was acquired by S-plot combined with P < 0.01 screening: N-acetylglycoprotein,isoleucine,lactic acid,O-acetylglycoprotein,alanine,choline,glutamic acid,acetate,trimethylamine oxide and creatine.Finally,the differential metabolites were analyzed to obtain 4 depression-related pathways.Among them,the D-glutamine and D-glutamic acid metabolism pathways may be the main pathways for CSE to exert the antidepressant effects.