Study On The Antidepressant Effect And Mechanism Of Peiyuan Jieyu Recipe

Depression with mood disorder as the main clinical manifestation is a comprehensive mental illness.It is characterized by easy incidence,prone to suicide,easy disability,and recurrent episodes,which seriously affects the work and life of patients.It takes the deep burden to family and society.Intense competition and fast-paced environment have led to an increase incidence of depression.And the patients are getting younger.At present,the main clinical treatment is chemical medicine,but the efficacy is not ideal.In recent years,more and more Chinese medicine research about depression has been carried out,and the effect is also very obvious,which provides a new method for the research and treatment of depression.In the Chinese Traditional medicine theory,the main cause of depression is Ganqi Yujie and Shuxie Buchang.Doctors mainly use Shugan Liqi Jieyu,with Zibu Ganshen,Buyi Xinpi and other methods of treatment in clinical.Sini San has the function of Sugan Jieyu.Tiansi Yin's effect is Bushen Anshen.The combination of the two is Peiyuan Jieyu Formula,which is in line with the theory of Chinese medicine for depression treatment.At the same time,modern research shows that whether a single-flavor drug(Bajitian,Tusizi,Chaihu,etc.),or the prescription Sini San(effective ingredients,effective sites and drug-containing serum,etc.)have good antidepressant efficacy.The Inflammatory factor hypothesis of depression suggests that depression is closely related to activation of the immune system and Inflammatory responses.Our previous study also found that compared with the blank group,the serum Inflammatory factor content of the model group was significantly increased,and the agents improved the depression-like behavior and decreased the serum Inflammatory factor content.In this experiment,the anti-depressant effect of Peiyuan Jieyu Formula was evaluated by the commonly used depression model,and the anti-depressant mechanism was explored by using the Inflammatory factor hypothesis as the entry point.1.Anti-depressant effect of Peiyuan Jieyu Formula on glucocorticoid-induced model rats and regulation of hippocampal neuronsObjective:To study the anti-depressant effect of Peiyuan Jieyu Formula and explore its anti-depressant mechanism.Methods:The rat model of depression was induced by subcutaneous injection of hydrocortisone injection.The depression status was evaluated by weight and SPT.The neonatal proliferation and differentiation phenotype in hippocampus were labeled by immunofluorescence.Results:The body weight growth rate and sucrose preference rats of the model were significantly decreased(p<0.01).Tiansi Yin,Sini San and the low doses of Peiyuan Jieyu Formula could improve the above-mentioned depression-like performance(p<0.05 or p<0.01).The average fluorescence intensity of Brdu in the model was significantly decreased(p<0.05),and the number of cells labeled with Brdu-GFAP and Brdu-Neun was decreased.Tiansi Yin,Sini San and the low doses of Peiyuan Jieyu Formula increased the average fluorescence intensity of Brdu and the number of cells labeled by Brdu-GFAP and Brdu-Neun.The low doses of Peiyu Jieyu Formula was significantly different(p<0.05).Conclusion:Tiansi Yin,Sini San and Peiyuan Jieyu Formula can produce antidepressant-like effects,and the mechanism may be associated with increased neuronal proliferation and differentiation.2.Anti-depressant effect and anti-inflammatory mechanism of Peiyuan Jieyu Formula on glucocorticoid-induced model ratsObjective:To study the anti-depressant effect of Peiyuan Jieyu Formula and explore its anti-depressant mechanism.Methods:The rat model of depression was established by subcutaneous injection of hydrocortisone injection.The depression status of rats was evaluated by weight and OFT.The contents of IL-1?,TNF-? and IFN-? in serum were detected by radioimmunoassay.The content of CRP in serum was detected by ELISA.The contents of IL-1?,TNF-? and IFN-? in brain homogenate were detected by ELISA.The free radical content in brain homogenate was determined.The immunohistochemical method was used to determine expression level of the microglia(IBA-1)in hippocampus.Results:The weight growth rate,horizontal exercise level,vertical movement level,total exercise,and total exercise distance of the model rats were significantly decreased(p<0.01),and the central residence time was significantly increased(p<0.01).Tiansi Yin and Sini San and Peiyuan Jieyu Formula can improve the above-mentioned depression-like manifestations in different degrees or different aspects(p<0.05 or p<0.01).Tiansi Yin,Sini San and Peiyuan Jieyu Formula can increased the content of IL-1?,TNF-a and IFN-y in serum(p<0.05 or p<0.01).Sini San significantly increased serum CRP content(p<0.05).The low and high dose Peiyuan Jieyu Formula significantly reduced the content of IL-1? in brain tissue homogenate(p<0.05).Each prescription can obviously reduce the TNF-a content(p<0.01).Peiyuan Jieyu Formula can reduce the IFN-? content(p<0.01).The effect of reversing the lowering of MDA content of Tiansi Yin and Sini San was significant(p<0.05 or p<0.01).And each prescription could significantly increase the SOD content(p<0.05 or p<0.01).Sini San and the medium and high doses of Peiyuan Jieyu Formula can reduce the hydroxy freedom.The brown-yellow microglia in the hippocampus under the microscope were changed from resting state to active state,and the model is obviouser than the control group(p<0.01).Individual prescription could reduce the average optical density of microglial(p<0.05 or p<0.01).Conclusion:Tiansi Yin,Sini San and Peiyuan Jieyu Formula can produce anti-depressant-like effects.The mechanism may be related to the reduction of central oxidative damage and the anti-Inflammatory effect with the reducing of central cytokine levels and microglia activation.3.Anti-depressant effect and mechanism of Peiyuan Jieyu Formula on chronic stress combined with LPS model miceObjective:To study the anti-depressant effect of Peiyuan Jieyu Formula and explore its anti-depressant mechanism.Methods:After 10 days of restraint plus noise stimulation,LPS(1 mg/kg)was injected intraperitoneally to establish a depression model.The immobility time of FST and TST was recorded.The serum levels of TNF-a and IFN-? were determined by ELISA.The expression of IDO mRNA in hippocampus was determined by immunohistochemistry.The expression of TRP,5-HT,KYN and KA in serum was determined by HPLC-MS/MS.Results:Tiansi Yin,Sini San and Peiyuan Jieyu Formula could shorten the immobility time of FST and TST in model mice(P<0.01).Tiansi Yin,Sini San and Peiyuan Jieyu Formula was significantly reduced the TNF-a content in the serum of model mice(p<0.05 or p<0.01).The effect of Sini San and the medium and high doses Peiyuan Jieyu Formula on IFN-? was significant(p<0.05 or p<0.01).Under the microscope,the brown-yellow microglia in the hippocampus were changed from resting state to active state,and the model group was significantly more than the normal group(p<0.01).Tiansi Yin,Sini San and the medium and high doses of Peiyuan Jieyu Formula can significantly decreased the expression of IB A-1 in hippocampal microglia(p<0.05 or p<0.01).Sini San and Peiyuan Jieyu Formula in reducing hippocampal IDO mRNA expression were obvious(p<0.05 or p<0.01).Tiansi Yin,Sini San and Peiyuan Jieyu Formula can significantly reduce KYN content and increase KYN/TRP ratio(p<0.01).Tiansi Yin can significantly reduce KA content(p<0.05).The KYN/KA ratio was significantly reduced by the low dose of Peiyuan Jieyu Formula(p<0.01).Conclusion:Tiansi Yin,Sini San and Peiyuan Jieyu Formula have a good anti-depressant effect in chronic stress combined with LPS model mice.The mechanism may be related to reducing the activation and synthesis of IDO,regulating the metabolic pathway of TRP-KYN and the anti-Inflammatory effect with reducing of TNF-a,IFN-y Inflammatory factor content and inhibiting microglia activation.