Effect Of Orcinol Glucoside On Depression-like Behavior Of Rats With Chronic Unpredictable Mild Stress And Its Potential Mechanism

Depression is a complex disease pathogenesis, it is great harm to human health,primarily selected5-serotonin reuptake inhibitor(SSRI)、norepinephrine reuptakeinhibitors and monoamine oxidase inhibitors on current antidepressant drugs, but ithave side effects. So, now scholars tend to investgate safe and effective herbalmedicines. Oricinol glucoside is a compound isolated from Curculigo, in vitroexpremental results show that it has a good role in neuroprotection.This study using achronic mild stress to establish rat depression model, and to explor the possible role ofOG antidepressant molecular mechanism.Obective: The study established a depression rat model using chronic unpredictablemild stress (CUMS), after a successful model rats was given Orcinol glucoside (OG),to observe the effect of OG on CUMS rats. And to explore the possible role of OGantidepressant mechanism.Methods:1. Establish a chronic unpredictable mild stress (CUMS) in the rat model of depression14male adult Sprague-Dawley rats were randomly divided in two groupaccording to the weihgt, the normal group and the model group (CUMS group). The rats were housed alone and exposed to a chronic unpredictable mild stressors in3weeks, the rats were tests with behavioral experiments indicate that stimulation ofstress model of depression. Measurement of serum corticosterone (CORT) levels byenzyme-linked immunosorbrnt assay, using RT-PCR to detect the expression of CRHmRNA in the hypothalamus.2. OG produces antidepressant mechanism in CUMS:54male adult Sprague-Dawley rats were housed alone and exposed to a chronicunpredictable stressors to induce CUMS, and then rats were randomly assigned to6groups,including an unhandled control group (control group)、a chronic unpredictablemild stress group(CUMS group)、3OG treatment groups (low-dose group1.5mg/kg、medium-dose group3mg/kg、high-dose group6mg/kg)，and a fluoxetine-treated CUMSgroup (positive group). Besides the normal group, the other groups were receivingdifferent stress in3consequent weeks. After2weeks of stress stimulate, dosageaccordance with fluoxetine group2mg/kg, OG low-dose group1.5mg/kg, OGmedium-dose3mg/kg, OG high-dose group6mg/kg, the CUMS group and the normalsaline group，and the intragastric administration volume is2ml/200g once a day,a totalof7days. The serum levels of corticosterone (CORT) in different group were observedby a commercially available enzyme-linked immunosorbent assay. In22th to26th day,we taked the behavioral tests on rats, including open-field test、sucrose preference test、force-swimming test、tail-suspension test. And detect the CRH mRNA expression inthe hypothalamus， protein levels of BDNF and phosphorylated-ERK1/2in thehippocampus.Results:1. After21consecutive days of a chronic unpredictable mild stress, established therats model of depression successfully. The concentration of CORT in serum was increaed, expression of CRH mRNA in the hypothalamus was increased in CUMSgroup.2. In CUMS, open-field test, fluoxetine group and OG group (1.5mg/kg) tosignificantly increase rearing，and also improved the crossed、grooming.Sucrosepreference test，Fluoxetine group and OG groups(1.5,3,6mg/kg) to significantlyincrease the sucrose preference index, Fluoxetine group and OG groups(1.5,3,6mg/kg)to significantly shorten the immobility time and increased the swimming timeinforce-swimming test. In the tail-suspension test, fluoxetine group and OG groups(1.5,3,6mg/kg) to significantly shorten the immobility time. The serum levels of CORTwas reduced and the CRH mRNA expression in the hypothalamus was also decreasedby the OG treatment, the hyperactivity of HPA axis in CUMS rats was reversed.proteinlevel of BDNF and phosphorylated-ERK1/2were both up-regulation in thehippocampus. CUMS group could increased the expression of synaptotagmin I andsynaptic I mRNA in the hypothalamus.Conclusion:21consecutive days of a chronic unpredictable mild stress, toestablished the rats model of depression successfully. OG (1.5,3,6mg/kg) couldalleviate the CUMS rats behaviors associated with depression, its mechanism may berelated to inhibiting activity of HPA axis and increase the expression of BDNF in thehippocampus and p-ERK1/2.