Study On The Effect And Mechanisms Of Shuxiefang-1 On The Emotional And Metabolic Changes In CUMS-treated Mice

Objective:This study was designed to investigate the effects of Shuxiefang-1 on emotion and metabolism in mice treated with chronic unpredictable mild stress(CUMS).Methods:1.CUMS mouse model:mice were subjected to 6-8 weeks of chronic unpredictable mild stress.At the end of the CUMS session,sucrose preference experiment,forced swimming experiment,tail suspension experiment,open field experiment,and elevated cross maze were performed.2.Shuxiefang-1 treatment;Shuxiefang-1 was administreated by gastric gavage daily.Body weight and random blood glucose were monitored weekly.Emotional changes were measured by behavioral experiments.Metabolic changes were evaluated by glucose tolerance test(GTT),insulin tolerance test(ITT),energy metabolism measurement etc.3.Real-Time PCR,Western Blot and ELISA were applied to measure the expression levels of target genes and proteins respectively.Results:1.CUMS slowed down the weight gain of mice,increased random blood glucose,decreased glucose tolerance,and increased overall energy metabolism,but had no significant effect on the serum levels of TC,TG,ALT,AST.2.Shuxiefang-1 significantly protected mice from CUMS-induced emotional dysfunction,which was shown by alleviated depression-like behavior and anxiety-like behavior.3.Shuxiefang-1 prevented CUMS-induced changes in glucose metabolism and energy metabolism,including body weight,random blood glucose,glucose tolerance,oxygen consumption,carbon dioxide production,and food intake.4.Shuxiefang-1 regulates the expression of emotion-related genes,which is characterized by increasing the concentration of 5-HT in hippocampus and cerebral cortex,stimulating the expression of synaptic protein SYP and drebrin,promoting AMPK phosphorylation,increasing BDNF and restoring the expression of the rhythm genes PER2 and PER3 in multiple brain regions.5.Shuxiefang-1 regulates the expression of genes related to liver metabolism,including FASN,ACC-1,AMPK,but has no effect on G-6-pase and PGC-1?.Conclusions:CUMS causes depression-like and anxiety-like behavioral changes and interferes with glucose,lipid and energy metabolism in mice.It can be used as an animal model for the study of liver stagnation syndrome in traditional Chinese medicine.Shuxiefang-1 can effectively counter the CUMS-induced emotional disorders,via increasing 5-HT concentration,restoring the rhythm of circadian clock gene PER2/3 and improving synaptic plasticity.In addition,Shuxiefang-1 can moderately alleviate the metabolic changes caused by CUMS.