Study On The Antidepressant Effects And 5-HT/BDNF Mechanisms Of Composition Drug-group Of Xiaoyao Powder

Objective:To obtain the optimum ratio of drug team from Xiaoyao Powder decomposed recipes used to treatment of antidepressant,researching the effects on the CUMS model mice and studying glutamate induce hippocampal neurons neurotoxicity,revealing the antidepression effect of the drug team and its 5-HT/BDNF pathway mechanism.Methods:(1)Chai Hu,Dang Gui,Bai Shao,and Bo He were design into 1,2,3,4,5(10.2 g/kg,17.55 g/kg,12.675 g/kg,18.3 g/kg,6.825 g/kg)five proportion groups by Uniform Design.The effects on mouse tail suspension/swimming test immobility time of different proportion groups were observed and combining the mathematical regression calculation method to filter out the best compatibility proportion of antidepressant effects,further screening of mint dosage to used as the following study of decomposed recipes drug-group(referred as Chai Dang Bo drug-group).(2)The CUMS-induced depression mice model prepared by using chronic unpredictable mild stress and isolated feeding for 6 weeks was used to observe the antidepressant effect of Chai Dang Bo drug-group.On the third week,the CUMS-induced depression mouse were orally administrated with Xiaoyao Powder(30g/kg),Chai Dang Bo drug-groups(16.43g/kg,21.90g/kg)and amitriptyline(10mg/kg)for 4 weeks.The body weight,autonomic activity,sucrose preference percentage,and spatial memory ability in Morris test etc.were observed to evaluate the antidepressant effect of Chai Dang Bo in CUMS-induced depression mouse.And the level of BDNF and 5-HT in serum and the content of 5-HT in hippocampus were detected by ELISA.(3)Behavioral responses induced by 8-OH-DPAT(5-HT1A receptor agonist)and DOI(5-HT2A receptor agonist)in mice were studied to explore the effects of decomposed recipes drug-team on 5-HT1A/2A receptors.(4)the protective effect of the decomposed recipes drug-team drug containing serum on the Glutamate induced primary cultured rat hippocampal neural cells neurotoxicity was observed.The content of 5-HT and BDNF in cell supernatant was determined by ELISA.Results:(1)the proportion 1(10.2 g/kg)drug group of Xiaoyao Powder decomposed recipes can significantly reduce the tail suspension and swimming immobility time of CUMS-induced depression mouse with no effect on the spontaneous activity of normal animal;and the remaining proportion drug groups had no effect on the mouse tail suspension and.swimming immobility time,based on the proportion of 1,composed of Chai Hu,Dang Gui,Bo He,the prescription wasdetermined,as the prescription drug Xiaoyaosan team for further research.(2)Compared with model group,Xiaoyao Powder decomposed recipes drug groups(Chai Dang Bo 16.43g/kg,21.90g/kg)could significantly increase the autonomic activities and sucrose consumption of CUMS-induced depression mice(P<0.01)and shorter incubation period of positioning navigation in morris water maze test(P<0.05);Xiaoyao Powder decomposed recipes drug group(16.43g/kg)significantly increase target quadrant moving distance and entering times of effective regional in space exploration experiment(P<0.01).Xiaoyao Powder decomposed recipes drug groups(16.43 g/kg,21.90 g/kg)can significantly increase the level of BDNF and 5-HT in serum and the.content of 5-HT in hippocampus of CUMS-induced depression mice.(3)Xiaoyao Powder decomposed recipes drug groups(16.43 g/kg,21.90 g/kg)can decrease the head twitch responses induced by DOI in mice;Xiaoyao Powder decomposed recipes drug group(21.90g/kg)showed the synergistic effect with 8-OH-DPAT on 5-HT like behaviors in mice.(4)Drug team containing serum of Xiaoyao Powder decomposed recipes can increase MTT methods' OD value of glutamate induce hippocampal neurotoxicity cell,decreasing the LDH activity in the cell supernatant.Containing serum(3%,4.8%)can significantly increase the content of BDNF in supernatant of the damaged cell(P<0.05),and 3%containing serum significantly increase 5-HT levels in the cell supernatant(P<0.05).Conclusion:(1)Drug team(Chai Dang Bo group)of Xiaoyao Powder decomposed recipes composed by Chai Hu,Dang Gui,and Bo He has antidepressant active.And it had behavioral improved effect on stress depression model mice and CUMS depression model mice.(2)Chai Dang Bo group with antidepressant effect was relate to improve the serum BDNF and serum/hippocampus 5-HT level of CUMS-induced depression mice model.Its may impact on the 5-HT system by agitated 5-HT1A receptor and antagonized 5-HT2A receptor.(3)the containing serum of Chai Dang Bo group has protective effect on the toxicity of rat hippocampal neurons induced by glutamate,and can increase the content of 5-HT/BDNF in the cell supernatant,further the results showed that antidepressant action of the drug team is relate to the 5-HT/BDNF pathway.