Methanol stem bark extract of Adansonia digitata ameliorates chronic unpredictable mild stress-induced depression-like behavior: Involvement of the HPA axis, BDNF, and stress biomarkers pathways

2019 ◽  
Vol 30 (3) ◽  
Author(s):  
Aishatu Shehu ◽  
Mohammed Garba Magaji ◽  
Jamilu Yau ◽  
Abubakar Ahmed
Keyword(s):  
Plasma Cortisol ◽  
Preference Test ◽  
Stem Bark ◽  
Bark Extract ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Adansonia Digitata ◽  
Object Recognition Test ◽  
Sod Activity

Abstract Background Adansonia digitata L. (Malvaceae) is used locally in the management of depressive illnesses, and its antidepressant-like effect has been previously reported. The present study was aimed at determining the effect of the methanol extract of the stem bark of A. digitata (MEAD) on chronic unpredictable mild stress (CUMS) and the possible mechanism responsible for its antidepressant activity. Methods Acute toxicity of MEAD was determined using the OECD guideline 420. The CUMS model was used to induce depression, and behavioral tests such as sucrose preference test (SPT), open field test (OFT), novel-object recognition test (NORT), and tail suspension test (TST) were carried out in mice. The concentrations of plasma cortisol and brain-derived neurotrophic factor (BDNF) protein in the brain were assessed using enzyme-linked immunosorbent assay kits. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were assessed using colorimetric methods. Results The LD50 was established to be ≥5000 mg/kg. On CUMS-induced depression, MEAD significantly (p ≤ 0.05) and dose dependently reversed the weight loss, increased the line-crossing activity in OFT, increased sucrose consumption in SPT, decreased the duration of immobility in TST, and increased the novelty exploration time in NORT. The MEAD extract significantly (p ≤ 0.05) and dose dependently increased the levels of BDNF, decreased the levels of plasma cortisol, increased the levels of total SOD activity, and decreased the levels of plasma MDA. Conclusion Our findings show that MEAD ameliorates CUMS-induced depressive-like behavior and its effect is possibly mediated via the neuroendocrine, neurotrophic, and oxidative stress pathways.

scholarly journals Crassifoside H ameliorates depressant behavior in chronic unpredictable mild stress rats by improving HPA axis dysfunction and inhibiting inflammation in hippocampus

2020 ◽  
Vol 19 (8) ◽  
pp. 1693-1699
Author(s):  
Huina Li ◽  
Kefan Wu ◽  
Yue Zhang ◽  
Ning Li ◽  
Kaijin Wang
Keyword(s):  
Hpa Axis ◽  
Mechanism Of Action ◽  
Therapeutic Potential ◽  
Preference Test ◽  
Antidepressant Effect ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Tnf Α ◽  
Sucrose Preference Test

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

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 ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Preference Test ◽  
Camp Response Element Binding ◽  
Sucrose Preference ◽  
Antidepressant Effect ◽  
Force Swim Test ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Traditional Chinese Herbal Medicine ◽  
Bdnf Signaling

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.

scholarly journals Emodin Prevented Depression in Chronic Unpredicted Mild Stress-Exposed Rats by Targeting miR-139-5p/5-Lipoxygenase

2021 ◽  
Vol 9 ◽  
Author(s):  
Teng Zhang ◽  
Can Yang ◽  
Jiang Chu ◽  
Lin-Na Ning ◽  
Peng Zeng ◽  
...  
Keyword(s):  
Psychosocial Stress ◽  
Glycogen Synthase ◽  
Quantitative Polymerase Chain Reaction ◽  
Preference Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Related Factor ◽  
Mild Stress ◽  
Nissl Staining ◽  
Force Swimming Test ◽  
Underlying Mechanisms

BackgroundThe use of medicinal plant ingredients is one of the goals of developing potential drugs for treating depression. Compelling evidence suggests that anti-inflammatory medicines may block the occurrence of depression. We studied the effect of a natural compound, emodin, on the development of psychosocial stress-induced depression and the underlying mechanisms.MethodsChronic unpredicted mild stress (CUMS) for 7 weeks was performed to replicate psychosocial stress in rats. The sucrose preference test, force swimming test, and open field test were used to evaluate their behaviors. The differentially expressed proteins in the hippocampus were analyzed using proteomics. Nissl staining and Golgi staining were used to detect the loss of neurons and synapses, immunohistochemical staining was used to detect the activation of microglia, and the enzyme-linked immunosorbent assay was used to detect the levels of pro-inflammatory cytokines. Western blotting, immunofluorescence, and quantitative polymerase chain reaction were also performed.ResultsHippocampal inflammation with up-regulated 5-lipoxygenase (5-LO) was observed in the depressed rats after CUMS exposure. The upregulation of 5-LO was caused by decreased miR-139-5p. To observe the effect of emodin, we screened out depression-susceptible (DeS) rats during CUMS and treated them with emodin (80 mg/kg/day). Two weeks later, emodin prevented the depression behaviors in DeS rats along with a series of pathological changes in their hippocampi, such as loss of neurons and spines, microglial activation, increased interleukin-1β and tumor necrosis factor-α, and the activation of 5-LO. Furthermore, we demonstrated that emodin inhibited its excess inflammatory response, possibly by targeting miR-139-5p/5-LO and modulating glycogen synthase kinase 3β and nuclear factor erythroid 2-related factor 2.ConclusionThese results provide important evidence that emodin may be a candidate agent for the treatment of depression and established a key role of miR-139-5p/5-LO in the inflammation of depression.

scholarly journals NLRP1-Mediated Antidepressant Effect of Ketamine in Chronic Unpredictable Mild Stress Model in Rats

2020 ◽  
Vol 17 (4) ◽  
pp. 283-291 ◽  
Author(s):  
Feyza Aricioğlu ◽  
Canan Yalcinkaya ◽  
Ceren Sahin Ozkartal ◽  
Erdem Tuzun ◽  
Serap Sirvanci ◽  
...  
Keyword(s):  
Preference Test ◽  
Receptor Protein ◽  
Antidepressant Effect ◽  
Albino Rats ◽  
Depression Symptoms ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Nlrp1 Inflammasome ◽  
Immobility Time ◽  
Wistar Albino Rats

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.

scholarly journals Escitalopram Targets Oxidative Stress, Caspase-3, BDNF and MeCP2 in the Hippocampus and Frontal Cortex of a Rat Model of Depression Induced by Chronic Unpredictable Mild Stress

2021 ◽  
Vol 22 (14) ◽  
pp. 7483
Author(s):  
Vlad Dionisie ◽  
Adela Magdalena Ciobanu ◽  
Vlad Alexandru Toma ◽  
Mihnea Costin Manea ◽  
Ioana Baldea ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Frontal Lobe ◽  
Caspase 3 ◽  
Preference Test ◽  
Sucrose Preference ◽  
Fixed Dose ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Sucrose Preference Test

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.

scholarly journals ANTIDEPRESSANT-LIKE ACTIVITY OF FLOWERS OF TECOMELLA UNDULATA IN MICE SUBJECTED TO CHRONIC UNPREDICTABLE MILD STRESS

2019 ◽  
Vol 12 (1) ◽  
pp. 130
Author(s):  
Dinesh Dhingra ◽  
Deepak Deepak
Keyword(s):  
Young Male ◽  
Ethanol Extract ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Plasma Corticosterone ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Tecomella Undulata ◽  
Plasma Nitrite

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.

scholarly journals The Antidepressant-Like Effects of Shen Yuan in a Chronic Unpredictable Mild Stress Rat Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Jiang ◽  
Haixia Wang ◽  
Hong Huang ◽  
Jingwei Lv ◽  
Guirong Zeng ◽  
...  
Keyword(s):  
Panax Ginseng ◽  
Forced Swim Test ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Oxidative Markers ◽  
Immobility Time ◽  
Polygala Tenuifolia ◽  
Sucrose Preference Test

Depression is a common yet severe neuropsychiatric condition that causes imposes considerable personal, economic, and social burdens worldwide. Medicinal plant species (e.g., Panax ginseng and Polygala tenuifolia) demonstrate potent antidepressant-like effects with less toxicity and other side effects. Shen yuan prescription (SY), composed of Panax ginseng (GT) and Polygala tenuifolia (YT). The present study aimed to elucidate the effects of SY treatment on chronic unpredictable mild stress (CUMS) rats and study the underlying mechanism. Our results indicated that SY (67.5, 135, or 270 mg/kg) significantly reverses the depressive-like behaviors in rats with a 5-week CUMS exposure, as demonstrated by increased sucrose consumption in the sucrose preference test, and decreased immobility time in the tail suspension and forced swim test. Moreover, SY altered serum corticosterone levels, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and oxidative markers (SOD, CAT, and MDA), and increased the levels of hippocampal neurotransmitters (5-HT, DA, and NE) in rats exposed to CUMS. Furthermore, rats treated with SY showed a reduction in the protein expression of BDNF, p-TrkB, p-Akt, and p-mTOR proteins induced by CUMS exposure in the hippocampus. In conclusion, SY prevented depressive-like behaviors in CUMS-exposed rats by preventing hypothalamus-pituitary-adrenal axis dysfunction, decreasing the levels of the neurotransmitters, minimizing oxidative stress, suppressing neuroinflammation, and activating the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway, all of which are the key players in the pathological basis of depression.

scholarly journals Antidepressant effect of methanol stem bark extract of Adansonia digitata: involvement of monoaminergic, nitric oxide and cholinergic pathways

2020 ◽  
Vol 10 (1) ◽  
pp. 84-92
Author(s):  
Aishatu Shehu ◽  
Mohammed Garba Magaji ◽  
Jamilu Yau ◽  
Abubakar Ahmed
Keyword(s):  
Nitric Oxide ◽  
Receptor Antagonist ◽  
Antidepressant Activity ◽  
Stem Bark ◽  
Bark Extract ◽  
Antidepressant Effect ◽  
Adansonia Digitata ◽  
Receptor Antagonists ◽  
Cholinergic Pathways ◽  
Stem Bark Extract

Introduction: Hausa people of north-western Nigeria were reported to utilize the plant Adansonia digitata for the management of depressive illnesses in an ethnobotanical survey. Thus, this study aimed to establish the mechanism(s) via which methanol stem bark extract of A. digitata (MEAD) exhibits antidepressant activity in mice. Methods: Antidepressant activity of MEAD was evaluated using tail suspension test (TST) at doses of 250, 500 and 1000 mg/kg. For the mechanistic studies, mice were pre-treated with sulpiride (50 mg/kg), prazosin (1 mg/kg), yohimbine (1 mg/kg), metergoline (1 mg/kg), cyproheptadine (3 mg/kg), L-arginine (50 mg/kg), N omega-nitro-L-arginine (L-NNA; 50 mg/kg), atropine (1 mg/kg) and naloxone (2 mg/kg) 15 minutes prior to MEAD (1000 mg/kg) administration, then antidepressant activity was assessed using TST one hour later. Data were analyzed using one-way ANOVA followed by Bonferroni post hoc test. Results: The extract (at doses of 250, 500 and 1000 mg/kg) significantly (P < 0.05) and dose-dependently decreased the duration of immobility in the TST. Sulpiride (D2 receptor antagonist), prazosin and yohimbine (α1 and α2 receptor antagonists, respectively), metergoline and cyproheptadine (5-HT1 and 5-HT2 receptor antagonists, respectively) significantly (P < 0.05) reversed the antidepressant effect of MEAD. On the other hand, L-NNA (NOS inhibitor) augmented the antidepressant effect of MEAD while L-arginine (nitric oxide substrate) had no effect on MEAD. However, atropine (muscarinic receptor antagonist) significantly (P < 0.01) augmented the antidepressant effect of MEAD. Conclusion: The antidepressant activity of methanol stem bark extract of A. digitata was established to be via the monoaminergic, nitric oxide and cholinergic pathways.

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