The Pharmacodynamics And Mechanism Of Compound Gaoziban Tablet In The Treatment Of Depression

Objective: The purpose of this study is to evaluate the efficacy of CGZBT on depression and explore its potential mechanism in order to provide scientific basis for the expansion of its clinical application.Methods: Adult male SD rats were used to establish CUMS induced depression.According to the results of the first SPT,the rats were divided into6 groups: Control group,Model group,0.4 g/kg CGZBT group,0.8 g/kg CGZBT group,1.6 g/kg CGZBT group and Fluoxetine group.At the second,4th and 6th weeks after modeling,the rats were tested for SPT.Intragastric administration was started at 4th week,once daily for 2 weeks.At the last week,rats in each group were subjected to OFT and FST.At the end of the experiment,the hippocampus and serum of rats were taken.After the end of the 6th weekend,the hippocampus and serum of rats were taken.The contents of 5-HT,NE,DA and 5-HIAA were detected by LC-MS,and the expression of IBA-1,TLR4,My D88,p-NF-κB and COX-2 in the hippocampus were detected by immunohistochemistry.Western blotting was used to detect the levels of TLR4,My D88,p-NF-κB,NF-κB,NLRP3,ASC,Caspase-1,pro-IL-1β,IL-1β and IL-18 in the hippocampus.The expression levels of TNF-α,IL-1β,IL-4,IL-6 and IL-10 in the collected serum were detected by ELISA.Results: Compared with Model group,CGZBT significantly increased the sugar preference rate of rats at 4th and 6th week（p<0.01 or p<0.05）;Compared with Model group,the total distance of movement of rats in CGZBT group was significantly increased（p<0.01）;In 0.8 g/kg CGZBT group and 1.6 g/kg CGZBT group,the distance through the center and number of grid crossings of CGZBT group were significantly increased（p<0.01 or p<0.05）;In addition,CGZBT treatment groups significantly reduced the immobile time of forced swimming（p<0.01 or p<0.05）.Compared with Model group,the concentration of 5-HT and DA in hippocampus of rats in CGZBT treatment groups were significantly increased（p<0.01 or p<0.05）;NE and 5-HIAA concentrations in hippocampus of 0.8 g/kg CGZBT group and 1.6g/kg CGZBT group significantly higher than Model group（p<0.01 or p<0.05）.In addition,the number of IBA-1 positive cells and the volume of microglia decreased in the treatment group.Compared with Model group,CGZBT could significantly reduce the levels of TNF-α,IL-6 and IL-1β in serum（p<0.01 or p<0.05）and significantly increased il-4 and IL-10 levels（p<0.01 or p<0.05）;Compared with Model group,the expressions of TLR4,ASC,Caspase-1 and IL-1β in the hippocampus of rats in CGZBT treatment groups were significantly down-regulated（p<0.01 or p<0.05）,the levels of My D88,p-NF-κB,NLRP3 and IL-18 in hippocampus of rats in 0.8 g/kg CGZBT group and 1.6 g/kg CGZBT group were significantly decreased（p<0.01 or p<0.05）.Conclusions: CGZBT regulated the concentration of central monoamine neurotransmitter in rats to alleviated depression-like behavior induced by CUMS.CGZBT exerts antidepressant effect by inhibiting TLR4/My D88/NF-κB signals,reducing the expression of NLRP3 inflammasome.This study showed that CGZBT can improve depression to some extent,and preliminarily clarified the mechanism of its anti-depression effect.