The Effect Of Peiyuan Jieyu Recipe On Acute Stress Depression Model And The Regulation Of TRP-KYN Metabolism

Depression is a kind of syndrome characterized by depression,slow thinking,and diminished will activity.WHO released data show that depression is expected to become the world's second largest burden of disease after coronary heart disease in 2020[1].Although there are more and more antidepressant drugs used in the treatment of clinical depression,but the effect is not satisfactory.Therefore,it is an effective supplement to the treatment of depression to find the treatment method and study its mechanism.Tiansi decoction and Sini powde composed of Peiyuan Jieyu Form?la,Sini powder from"Treatise on harmed by cold",is a classic Shugan Jieyu prescription.the anti depression effect of Sini Powder may be related to 5HT neurons,neurotrophic and hippocampal neurogenesis,Morinda oligosaccharide is the Effective constituent of Morinda officinalis in Tiansi decoction,is similar to fluoxetine[2,3],has a good antidepressant effect,semen cuscutae contains hypericin(0.076%-0.102%),which has good antidepressant effect.At present,more and more data show that various stress factors can activate TRP-KYN metabolic pathway may lead to abnormal changes in neuronal plasticity associated with active substances,which leads to the occurrence of depression,the metabolic disorder of TRP-KYN is one of the important links to cause neuronal plasticity.This paper aims to Sini powder and Tiansi decoction,combination as the carrier,to further study the effect and reg?glation of Tryptophan kynurenine metabolic pathways of central neuronal plasticity related active substances.1?Antidepressant effects of Peiyuan Jieyu Form?la and its reg?lation of TRP-KYN metabolic on the BALB/c mice model of depression induced by acute stressObjective To study the antidepressant effects of Peiyuan Jieyu Form?la,and the reg?lation of the Tryptophan-kynurenine(TRP-KYN)pathway.Methods 50 mice were randomly divided into model group?imipramine group?Tiansi decoction group?Sini powder group and Peiyuan Jieyu Form?la,The model of depression was induced by forced swimming,Each administration group was given intragastric administration before forced swimming,the interval was 4 hours,The immobility time in forced swimming test was acquired and analysed by Noldus EthoVision XT9 system.The content of TRP?KYN?C in serum were detected by using HPLC-MS/MS technique.The mRNA expression level of Tryptophan 2,3-dioxygenaes(TDO)in liver tissue were detected by using real-time PCR.Res?lts Acute stess,the immobility time of Balb/c mice was prolonged(p<0.05).The activity of TDO in liver tissue and the mRNA expression level of TDO increased(p<0.01).Tiansi decoction group?Peiyuan Jieyu Prescription co?ld shorten the immobility time of mice(<0.05).It co?ld reduce theTDO mRNA expression.The inhibitory effect of Quinolinic acid by Tiansi Liquid is more significant.2?Antidepressant effect of Peiyuan Jieyu Form?la and its Reg?lation of TRP-KYN metabolic on the rat model of depression induced by acute hydrocortisoneObjective To study the antidepressant effects of Peiyuan Jieyu Form?la,and the reg?lation of the Tryptophan-kynurenine(TRP-KYN)pathway.Methods The80 rats were randomly divided into control group?model group?fluoxetine group?Tiansi decoction group?Sini powder group?the low dose of Peiyuan Jieyu Form?la(0.435g/kg)?the medium dose of Peiyuan Jieyu Form?la(0.87g/kg)?the high dose group of Peiyuan Jieyu Form?la(1.74g/kg).Daily intraperitoneal injection of Hydrocortisone,Fluoxetine group?Tiansi decoction group?Sini powder group?high dose group and medium dose of Peiyuan Jieyu Form?la continued after administration of 21d,Open field experiment was used to observe the autonomous activities and inquiry activities of rats.Sucrose preference test was used to observe depressive behavior in rats.HPLC-MS/MS technique was used to detect the contents of TRP?KYN?QUIN?KYNA in serum.The mRNA expression level of TDO in liver tissue?IDO in hippocampus and cortex were detected by using real-time PCR.Res?lts The Fuoxetine group,Sini powder group,Peiyuan Jieyu Form?la co?ld improve the preference for sucrose in rats.The Fuoxetine group?Tiansi decoction group?Sini powder group?high dose group and medium dose of Peiyuan Jieyu Form?la can improve rat autonomous inquiry activities.The treatment group had obvious effect on the ratio of KYN/TRP,Tiansi decoction group and Peiyuan Jieyu Form?la middle dose group can improve the content of KYNA;Tiansi decoction group decoction group and fluoxetine group,Peiyuan Jieyu Formula middle dose group can decrease the content of QUIN;Tiansi decoction can reduce the expression of TDO mRNA.The Fuoxetine and Tiansi decoction can reduce the expression of IDO mRNA.3.The antidepressant effect and neuronal plasticity effects of Peiyuan Jieyu Formula on the model of depression induced by hydrocortisoneObjective Observe the antidepressant effect and neuronal plasticity effects of Peiyuan Jieyu Formula on the model of depression induced by hydrocortisone.Methods Use the rat model of depression induced by hydrocortisone,Daily intraperitoneal injection of corticosterone,fluoxetine group?Tiansi decoction group?Sini powder group?the low dose of Peiyuan Jieyu Form?la?the medium dose of Peiyuan Jieyu Form?la?the high dose group of Peiyuan Jieyu Formula continued after administration of 21d,The expression level of IDO?5-HT1A?CREB?BDNF?GR?NMDA?TrkB mRNA were detected by using real-time PCR.Res?lts Sini powder can increase the expression of GR mRNA.Sini powder and high dose group?medium dose group?low dose group of Peiyuan Jieyu Form?la can increase the expression of 5-HT1A mRNA.Fluoxetine can reduce expression of NMDA mRNA,and compared with the model group had significant difference,low dose group of Peiyuan Jieyu Form?la can increase the expression of TrkB(p<0.05);The cortex results showed that Fluoxetine,high dose group and medium dose of Peiyuan Jieyu Form?la can increase the expression of BDNF mRNA,Fluoxetine?the low dose and the medium dose of Peiyuan Jieyu Form?la can increase the expression of 5-HT1A mRNA,Sini powder decreased the expression of 5-HT1A mRNA,compared with the model group had significant difference(p<0.05).2.The effect on intracell?lar free calcium concentration of Peiyuan Jieyu Formula on the depression model induced by corticosterone.Objective Observe the effect on intracell?lar free calcium concentration of Peiyuan Jieyu Form?la on the depression model induced by corticosterone.Methods 40 rats were randomly divided into blank group?Fluoxetine group?model group?Tiansi decoction group,Sini powder group,and Peiyuan Jieyu Form?la.Daily intraperitoneal injection of corticosterone,Fluoxetine group?Tiansi decoction group,Sini powder group,Peiyuan Jieyu Form?la continued after administration of 21 d,the flow cytome was used to observe the concentration of free calcium in brain tissue.Res?lts The concentration of Ca2+ in model group was significantly higher than that in normal group,and there was significant difference(p<0.05);Tiansi decoction group,Sini powder group and Peiyuan Jieyu Form?la can significantly reduce the concentration of intracell?lar calcium,inhibit calcium overload,has good effect of neuroprotective effect.Conclusion:This experiment shows thatTiansi decoction and the Peiyuan Jieyu Form?la has the antidepressant effect on the model of depression induced by Acute forced swimming,The mechanism is related to the increase of TDO activity induced by stress,Tiansi decoction has a unique role in reg?lating QUIN metabolism,its mechanism needs further study.Tiansi decoction?Sini powde and the Peiyuan Jieyu Form?la show the antidepressant effect on the rat depression model induced by hydrocortisone,The antidepressant mechanism of Tiansi decoction is related to the decreasing of TDO in liver?decreasing expression and activity of IDO in brain,thus affecting the 5-HT energy system,Increasing the content of 5-HT;The antidepressant mechanism of Sini powde is related to the decreasing of TDO in liver?decreasing activity of IDO in hippocampus?increased expression of 5-HT1A,so as to increase the function of 5-HT neurons.Further study is needed to increase the expression of GR and decrease the expression of 5-HT1A of Sini powde in the hippocampus and cortex.The antidepressant mechanism of Peiyuan Jieyu Form?la is related to the decreasing of serum corticosterone,decreasing activity of IDO and TDO?decreasing expression of IDO and TDO,increased expression of 5-HT1A,Thus affecting the 5-HT system.Low dose of Peiyuan Jieyu Form?la significantly increased the expression of TrkB;the high dose group and medium dose of Peiyuan Jieyu Form?la can increase the expression of BDNF mRNA,There is a unique role in nerve protection.Tiansi decoction?Sini powde and the Peiyuan Jieyu Form?la against the concentration of free calcium in nerve cells induced by corticosterone,Tiansi decoction?Sini powde and the Peiyuan Jieyu Form?la has a neuroprotective effect.