Evaluation Of Therapeutic Markers Of Shuganjieyu Capsule In The Treatment Of Depression

Objective:Depression is a common mental illness,mainly manifested as depression,slow thinking,pessimism,self-blame and diet and sleep problems,seriously accompanied by suicidal tendencies.Depression not only mterferes seriously with the patients themselves,but also has negative effects on the family and society.At present,the drugs for treating depression are mainly western medicine,but they are often accompanied by side effects and drug resistance,so traditional Chinese medicines with small side effects have received more and more attention.Shuganjieyu capsule is a Chinese herbal preparation that has been shown to treat depressive symptoms.However,the antidepressant mechanism of the capsule is still poorly understood,and the efficacy evaluation system of the capsule in the treatment of depression is lacking.This problem is also an important scientific and technological issue affecting the development and modernization of antidepressant drugs in China,and also a bottleneck of the internationalization of TCM in China.Therefore,the Shuganjieyu capsule was studied in clinical samples and animal models.This study is divided into two parts:1.Comparing the expression level of candidate genes before and after the treatment of depressed patients,and analyze the correlation with depressive symptoms and cognitive function.Find and identify efficacy biomarkers related to the efficacy of the capsules.2.Observe the behavioral effect of Shuganjieyu capsule on WKY depressed rats,and explore its brain mechanism,aiming to provide a basis for the treatment of Shuganjieyu capsule in depression.Methods:art one,27 patients with mild and moderate depression before and after baseline and weekend using the Hamilton Depression Rating Scale(HAMD)to assess depression severity,Wechsler Adult Intelligence Scale(WAIS),Wechsler memory scale(WMS)to assess cognitive function,and then quantitative real-time PCR(qRT-PCR)technology to test the expression level of peripheral blood candidate genes in depression patients before and after capsule treatment.Finally,the correlation analysis and efficacy evaluation of the gene expression and clinical data were determined.Part two,Wistar-Kyoto(WKY)rats of the depressed animal model were selected as the experimental group,and Wistar rats were used as the control group(Wistar+CMC-Na).The experimental group was randomly divided into three groups:model group(WKY+CMC-Na),liver Shu group(WKY+SG)and fluoxetine group(WKY+FXT),followed by a 21-day treatment.Forced swimming test(FST),sucrose preference test(SPT),open field test(OFT),and morris water maze(MWM)were used to observe the behavioral differences of rats in each group.Part three,the expression differences of candidate genes in hippocampus,prefrontal cortex and corpus striatum brain regions were observed.Results:Part one,MMD patients were relieved by Shuganjieyu capsule(HAMD scores:baseline(14.00,8.50),8-week(4.00,5.25),(Z=-4.462,P<0.001)),and cognitive function recovered(WAIS scores:baseline(123.00±10.24),8-week(128.00±6.77),(t=4.372,P<0.001)).The expression of BDNF(baseline(1.68,1.71),8-week(2.30,2.04),(Z=2.781,P=0.005)),GDNF(baseline(0.74,0.84),8-week(0.97,1.21),(Z=2.159,P=0.031)),HTR2A(baseline(0.60,1.20),8-week(0.98,1.83),(Z=-1.994,P=0.046))and GRIA1(baseline(1.19,1.74),8-week(1.76,3.28),(Z=2.756,P=0.006))was up-regulated.The change rate of BDNF expression were correlated with depressive symptoms(r=-0.353,P=0.038)and cognitive function(r=0.398,P=0.022).Part two,after 21 days of intervention in each group,sucrose preference test in model group(WKY)(Wistar)(t=7.606,P<0.001)and sucrose preference in fluoxetine(Fluoxetine)compared with model group(WKY)(t=2.980,P=0.033).Forced swimming experiment showed increased mobility time in the model group(t=13.40,P<0.001)and in the group(Shuganjieyu)(t=4.485,P=0.003)and fluoxetine(t=4.559,P=0.001)compared with the model group.The results showed that the model group was significantly lower in motor distance(t=8.012,P=0.001)and t=8.691,P=0.001)(t=3.381,P=0.012)(t=3.241)and P=0.025)(t=3.658,P=0.012).Weight gain was significantly lower in the model group(t=17.08,P<0.001),and increased in the group(t=3.202,P=0.025)and fluoxetine(t=4.460,P=0.003)compared with the WKY group.In the Morris water maze experiment,rats in the target time were significantly higher than in the WKY group(t=3.550,P=0.006).Part three,in the prefrontal cortex of WKY rats,BDNF gene expression was reduced(t=3.840,P=0.005),and increased BDNF gene expression after intervention with Shuganjieyu capsule(t=2.936,P=0.019)or fluoxetine(t=3.424,P=0.009).In WKY rat corpus striatum,BDNF gene expression was decreased(t=2.996,P=0.017),and BDNF gene expression was increased after intervention with Shuganjieyu capsule(t=3.080,P=0.015)or fluoxetine(t=3.144,P=0.014).In the striatum of WKY rats,GDNF gene expression was also decreased(t=7.602,P<0.001),and its GDNF gene expression was increased by intervention with Shuganjieyu capsule(t=2.898,P=0.020)or fluoxetine(t=6.653,P<0.001).In the prefrontal cortex of WKY rats,HTR2A gene expression was increased(t=9.513,P<0.001),while HTR2A expression decreased after intervention with Shuganjieyu capsule(t=12.27,P<0.001)or fluoxetine(t=3.609,P=0.007).Conclusion:In clinical studies,patients with mild and moderate depression relieved depressive symptoms and cognitive function,The expression of BDNF,GDNF,HTR2A and GRIA1 was up-regulated.Correlation analysis found a significant correlation between BDNF and depressive symptoms,and significant correlation between BDNF and cognitive function.It is therefore concluded that BDNF may be used as a therapeutic marker of Shuganjieyu capsule in the treatment of clinical symptoms and cognitive function of MMD patients.In animal studies,Shuganjieyu capsule improved depression-like behavior in WKY rats.This study validated the involvement of BDNF,GDNF,and HTR2A in the prefrontal cortex and corpus striatum in antidepressant effects,reflecting the involvement of candidate genes in the pathophysiology of depression.Taken together,the experimental results show that BDNF can participate in the process of relieving the Shuganjieyu capsule in treating depression and serve as a marker for its efficacy in improving depressive symptoms.