scholarly journals The Antidepressant Effect ofAngelica sinensisExtracts on Chronic Unpredictable Mild Stress-Induced Depression Is Mediated via the Upregulation of the BDNF Signaling Pathway in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Jun Shen ◽  
Junjian Zhang ◽  
Min Deng ◽  
Yue Liu ◽  
Yuan Hu ◽  
...  

Angelica sinensis(AS), a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS-) induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF) and the phosphorylation of cAMP-response element binding protein (CREB) and extracellular signal-regulated protein kinase (ERK 1/2) were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg) normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB) were upregulated in the hippocampus.

2021 ◽  
Vol 22 (14) ◽  
pp. 7483
Author(s):  
Vlad Dionisie ◽  
Adela Magdalena Ciobanu ◽  
Vlad Alexandru Toma ◽  
Mihnea Costin Manea ◽  
Ioana Baldea ◽  
...  

In recent years, escitalopram (ESC) has been suggested to have different mechanisms of action beyond its well known selective serotonin reuptake inhibition. The aim of this study is to investigate the effects of escitalopram on oxidative stress, apoptosis, brain-derived neurotrophic factor (BDNF), Methyl-CpG-binding protein 2 (MeCP2), and oligodendrocytes number in the brain of chronic unpredictable mild stress-induced depressed rats. The animals were randomised in four groups (8 in each group): control, stress, stress + ESC 5 and stress + ESC 5/10. ESC was administered for 42 days in a fixed dose (5 mg/kg b.w.) or in an up-titration regimen (21 days ESC 5 mg/kg b.w. then 21 days ESC 10 mg/kg b.w.). Sucrose preference test (SPT) and elevated plus maze (EPM) were also performed. ESC improved the percentage of sucrose preference, locomotion and anxiety. ESC5/10 reduced the oxidative damage in the hippocampus and improved the antioxidant defence in the hippocampus and frontal lobe. ESC5/10 lowered caspase 3 activity in the hippocampus. Escitalopram had a modulatory effect on BDNF and the number of oligodendrocytes in the hippocampus and frontal lobe and also improved the MeCP2 expressions. The results confirm the multiple pathways implicated in the pathogenesis of depression and suggest that escitalopram exerts an antidepressant effect via different intricate mechanisms.


2021 ◽  
Author(s):  
Biyun Xu ◽  
Daiyu Xue ◽  
Runru Mai ◽  
Hailong liang ◽  
Qinghao Cai ◽  
...  

Abstract Backgrounds: Memory impairment is an important factor affecting the prognosis of depression, with unclear mechanism and lack of effective drugs. Our previous study has showed that Liuwei Dihuang decoction (LW) could alleviates depression and memory through upregulation of G protein-coupled receptor 30 (GPR30) - cAMP response element-binding protein (CREB) - brain-derived neurotrophic factor (BDNF). However, further confirmation is needed. In this study, we investigate whether G15, a GPR30 specific antagonist could reverse the effects of LW on depressive mood and spatial memory. Methods: Chronic unpredictable mild stress (CUMS) rat model was used, divided into normal group, model group, LW(7.81 g/kg/d ) group, LW(7.81 g/kg) + 10ug/d G15 group and LW + 40ug/d G15 group. The open field test (OFT) and sucrose preference test (SPT) were used to measure depression in rats, and the morris water maze (MWM) was used to test the learning memory of rats. The serum estrogen level was analysed by Elisa method. The GPR30, CREB and BDNF level of hippocampus were measured by quantitative real-time polymerase chain reaction and western blot analysis. Results: LW (7.81 g/kg/d) remarkably increased the intake of sugar water, lengthen ed the total distance and rearing times of OFT, shortened mean latency and times crossing the platform and time-spending during the platform quadrant of MWM in CUMS rats. LW also significantly increased serum level of estrogen and upgregulated the mRNA and protein level of GPR30, BDNF and protein level of CREB, while G15 reversed protective effect of LW on all of them. Conclusion: LW (7.81 g/kg/d) ameliorates depressive behavior and memory deficits associated with CMS-induced in rats. The mechanism may be mediated by hippocampal GPR30 – CREB - BDNF signaling pathway.


2020 ◽  
Vol 17 (4) ◽  
pp. 283-291 ◽  
Author(s):  
Feyza Aricioğlu ◽  
Canan Yalcinkaya ◽  
Ceren Sahin Ozkartal ◽  
Erdem Tuzun ◽  
Serap Sirvanci ◽  
...  

Objective NOD-like receptor protein 1 (NLRP1) inflammasome complex has been recently associated with chronic unpredictable mild stress (CUMS) model of depression. Our aim was to investigate whether ketamine-induced antidepressant effect is associated with suppression of NLRP1.Methods Wistar albino rats were divided into control, CUMS, CUMS+acute ketamine (a single 10 mg/kg dose) and CUMS+chronic ketamine (daily 10 mg/kg injections for 3 weeks) groups (n=10 for each group). Sucrose preference test and forced swimming test were performed to assess anhedonia and immobility time respectively for the severety of depression symptoms. Brain tissues were dissected and prefrontal cortex and hippocampus regions were used for real-time polymerase chain reaction (PCR) and immunohistochemical analysis.Results CUMS procedure significantly induced depressive-like symptoms whereas both acute and chronic ketamine treatment ameliorated them. mRNA expression levels of NLRP1, caspase 1, apoptosis-associated speck-like protein containing a CARD (ASC), NF-κB, endothelial nitric oxide synthase, IL-1β, IL-6, toll-like receptor 4 (TLR-4) and purinergic 2×7 receptor (P2X7R) and numbers of Iba- 1+and GFAP+glial cells were reduced by acute and/or chronic ketamine treatment.Conclusion In the present study for the first time upstream and downstream elements of the NLRP1 inflammasome complex are shown to be suppressed by ketamine thus reinforcing the involvement of NLRP1 in the physiopathology of depression.


2020 ◽  
Vol 19 (8) ◽  
pp. 1693-1699
Author(s):  
Huina Li ◽  
Kefan Wu ◽  
Yue Zhang ◽  
Ning Li ◽  
Kaijin Wang

Purpose: To investigate the antidepressant mechanism of action of Crassifoside H (CH) from the rhizomes of Curculigo glabrescens (Hypoxidaceae) in chronic unpredictable mild stress (CUMS)-induced rats.Methods: CUMS-induced rat depressant model was established. Behavioral tests, viz, sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST) were applied to assess the antidepressant effect of CH. Enzyme linked immunosorbent assay (ELISA) was used to assess thelevels of corticosterone (CORT), TNF-α and IL-1β in serum. Protein expressions of TNF-α, IL-1β and NLRP3 in rat hippocampus were determined by Western blot.Results: Crassifoside H significantly ameliorated CUMS-induced depressant-like behavior as the serum CORT level of CUMS rats. CH remarkably decreased TNF-α and IL-1β levels in serum and hippocampus of CUMS rats. Moreover, Crassifoside H significantly inhibited NLRP3 activation inhippocampus.Conclusion: The findings demonstrate that Crassifoside H has antidepressant effect on CUMS rats. The mechanism of action of CH may be at least partly due to the improvement of hypothalamic-pituitaryadrenal (HPA) axis dysfunction by decreasing serum CORT. These findings suggest that Crassifoside H has a therapeutic potential for the management of depression. Keywords: Crassifoside H, Antidepression, Curculigo glabrescens, Hypoxidaceae, Hypothalamicpituitary- adrenal axis, Inflammation, Corticosterone


Author(s):  
Dinesh Dhingra ◽  
Deepak Deepak

Objective: Flowers of Tecomella undulata have been reported to be a rich source of flavonoids such as rutin and quercetin. The present study was designed to evaluate the effect of ethanol extract of flowers of T. undulata on chronic unpredictable mild stress (CUMS)-induced depression in Swiss young male albino mice.Methods: The mice were subjected to CUMS for 21 successive days. Ethanol extract of the flowers (50, 100, and 200 mg/kg, p.o.) and fluoxetine (20 mg/kg, p.o.) per se was administered for 21 successive days to separate groups of unstressed and stressed mice. Tail suspension test (TST) and sucrose preference test were used to evaluate the effect of the extract on depression-like behavior in mice.Results: Extract of flowers of T. undulata (100 and 200 mg/kg) significantly decreased immobility period of stressed mice in TST, indicating significant antidepressant-like activity of the extract. Stress-induced reduced sucrose preference was significantly restored by the extract. There was no significant effect on locomotor activity of mice by the extract and fluoxetine. The extract significantly reversed stress-induced increase in brain malondialdehyde levels; plasma nitrite and corticosterone levels; and also significantly reversed the stress-induced decrease in reduced glutathione and catalase levels. There was no significant effect of the extract on brain MAO-A activity in both unstressed and stressed mice.Conclusion: These results indicated that ethanol extract of flowers of T. undulata showed significant antidepressant-like activity in mice subjected to CUMS, probably through alleviation of oxidative stress and decrease in plasma corticosterone levels.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Dehua Liao ◽  
Chuanfeng Lv ◽  
Lizhi Cao ◽  
Dunwu Yao ◽  
Yi Wu ◽  
...  

Accumulating evidence has demonstrated that oxidative stress is associated with depression. Our present study aimed at investigating the antidepressant effect and the possible mechanisms of curcumin (CUR) in chronic unpredictable mild stress- (CUMS-) induced depression model in rats. After exposure to CUMS for four weeks, the rats showed depressive-like behavior, and the depressive-like behaviors in CUMS-treated rats were successfully corrected after administration of CUR. In addition, CUR could effectively decrease protein expression of oxidative stress markers (Nox2, 4-HNE, and MDA) and increase the activity of CAT. CUR treatment also reversed CUMS-induced inhibition of Nrf2-ARE signaling pathway, along with increasing the mRNA expression of NQO-1 and HO-1. Furthermore, the supplementation of CUR also increased the ratio of pCREB/CREB and synaptic-related protein (BDNF, PSD-95, and synaptophysin). In addition, CUR could effectively reverse CUMS-induced reduction of spine density and total dendritic length. In conclusion, the study revealed that CUR relieves depressive-like state through the mitigation of oxidative stress and the activation of Nrf2-ARE signaling pathway.


2019 ◽  
Vol 4 (2) ◽  
pp. 72
Author(s):  
Gisella Intan Soetantyo ◽  
Mulyati Sarto

Depression is a disabling mental disorder, predicted to become the world's number 2 disability by 2020 by the World Health Organization (WHO, 2018). Chronic stress is one of the triggers for depression, causing an imbalance in brain chemicals and antioxidants levels. Although antidepressant is a common treatment, discomforting side effects has compromised its efficacy, prompting the search for alternative medicines. Chlorella vulgaris is a microalgae famous for its excellent protein and antioxidant content. In this study, C. vulgaris (360 mg/kg p.o.) potency of antidepressant in chronic unpredictable mild stress (CUMS) model of depression in female rats was evaluated compared to amitriptyline (2,25 mg/kg p.o.) for 14 days. Two types of C. vulgaris namely cultivation sourced and commercially-sold, were used. Sucrose preference test, forced swim test (FST) and open field test (OFT) were used as depression-like behaviour test to validate C. vulgaris effect. Adrenal glands were observed to further understand its effect on the stress organ. The CUMS method produced rats with depressive-like behaviour evidently by reduced body weight, sucrose preference, exploring behaviour in OFT, and increased immobility duration in FST. Furthermore, an increase in adrenal weight, fasciculata zone, and reticularis zone was observed. Both C. vulgaris significantly (p<0,05) reversed depressive-like behaviour in rats subjected to CUMS, but not the size of adrenal glands. This finding indicated both types of C. vulgaris has the potential to be an alternative antidepressant but because of the short duration of treatment, it’s speculated that C. vulgaris may not have exhibited enough difference structurally yet. 


Author(s):  
Dinesh Dhingra ◽  
Deepak Deepak

Objective: Flowers of Tecomella undulata have been reported to be a rich source of flavonoids such as rutin and quercetin. The present study was designed to evaluate the effect of ethanol extract of flowers of T. undulata on chronic unpredictable mild stress (CUMS)-induced depression in Swiss young male albino mice.Methods: The mice were subjected to CUMS for 21 successive days. Ethanol extract of the flowers (50, 100, and 200 mg/kg, p.o.) and fluoxetine (20 mg/kg, p.o.) per se was administered for 21 successive days to separate groups of unstressed and stressed mice. Tail suspension test (TST) and sucrose preference test were used to evaluate the effect of the extract on depression-like behavior in mice.Results: Extract of flowers of T. undulata (100 and 200 mg/kg) significantly decreased immobility period of stressed mice in TST, indicating significant antidepressant-like activity of the extract. Stress-induced reduced sucrose preference was significantly restored by the extract. There was no significant effect on locomotor activity of mice by the extract and fluoxetine. The extract significantly reversed stress-induced increase in brain malondialdehyde levels; plasma nitrite and corticosterone levels; and also significantly reversed the stress-induced decrease in reduced glutathione and catalase levels. There was no significant effect of the extract on brain MAO-A activity in both unstressed and stressed mice.Conclusion: These results indicated that ethanol extract of flowers of T. undulata showed significant antidepressant-like activity in mice subjected to CUMS, probably through alleviation of oxidative stress and decrease in plasma corticosterone levels.


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