Explore The Mechanism Of Antidepressant TZ Based On 5-HT In The Brain

Depression is a psychological disease with no particularly effective therapy now,which affects people's daily activities seriously.The present study examined anti-depressive activity of the compound herbal formula called TaiZi(TZ)capsule,consisting of Radix Pseudostellariae,Radix Pueraria and Herba Epimedii,and presented a potential effective natural productive drug for anti-depression.First,we detected the whole pharmacological activities of TZ by proteomics experiments.Then the anti-depression effect of TZ was test in animal depression models like learned helplessness model,chronic unpredictable mild stress model and endocrine disturbance model by tail suspension test,forced swimming test.The changes of neurotransmitters in animal brain was determined.Results show that the immobility time of animals taking TZ is significantly reduced in the tail suspension test and forced swimming test.In reserpine model and 5-HTP model mice,TZ also shows a good antidepressant effect.Serotonin and norepinephrine levels was obviously improved in TZ mice than control group,while no significant difference was observed with dopamine.mRNA expression was detected using real-time PCR assay and protein expression was investigated using Western blot assay.Tryptophan hydroxylase II(TPH2),the speed limit enzyme of serotonin synthesis can be increased effectively by TZ and its component icariin.In vitro,study in C17.2 cell line shows the same results.Neuron restrictive silencer factor(NRSF)was abnormally activated in depression model mice and bind to neuron restrictive silencer element(NRSE)to repress TPH2 transcription.By construction of a TPH2 promoter plasmid and a NRSE-knockout TPH2 promoter plasmid,we confirmed that NRSE and NRSF play a significant role in TPH2 upregulation.At last,we explore other mechanism of the antidepressant effect of TZ.In conclution,this study fully confirmed the antidepressant activities of TZ,and found that increase of TPH2 in brain by the component of TZ icariin is an impotent mechanism of TZ's antidepression effect.And this study would give us a new perspective for the development of anti-depression drugs based on NRSF-TPH2 signaling and the Chinese medicines.