Harmane suppresses microglial neuroinflammatory response and induce antidepressant-like effect in rats

2017 ◽  
Vol 41 (S1) ◽  
pp. S366-S366 ◽  
Author(s):  
F. Aricioglu ◽  
G. Arkan ◽  
C. Kandemir ◽  
S. Sirvanci ◽  
C. Ozkartal ◽  
...  

ObjectiveHarmane is a beta-carboline, which binds to imidazoline receptors and it has been previously shown that it may have an antidepressant effect when administered acutely. This study is planned to investigate the effect of harmane on chronic unpredictable mild stress (CUMS) model and microglial (Iba-1) immunoreactivity in the same model as markers of neuroinflammation.MethodsMale Wistar Albino rats (290–360 g) were divided into groups such as control (saline), CUMS, CUMS + Imipramine (20 mg/kg; i.p.), CUMS + Harmane5 (5 mg/kg; i.p.), CUMS + Harmane10 (10 mg/kg; i.p.) groups (n = 10–12 in each). In CUMS model, various stressors were applied for 40 days. On day 20, harmane administration was started for 20 days. At the end, sucrose preference and forced swimming tests were performed. Then, brains were removed with paraformaldehyde perfusion for Iba-1 immunohistochemical analysis in hippocampus. One-way analysis of variance and Tukey's test were used for statistical analysis.ResultsThe time of immobility in forced swim test was significantly reduced while sucrose preference was increased in Imipramine and CUMS + harmane10 groups. In immunohistochemical experiments, Iba-1 were overexpressed in CUMS group and Harmane significantly reduced the overexpression of Iba-1.ConclusionOur results suggest that chronic administration of harmane has an antidepressant-like activity in chronic stress model of depression. These results support the notion of imidazoline receptors involvement in depression by modulating neuroinflammation and at least a part of its antidepressant effect might be through modulating microglial activation as a reflection of neuroinflammation.This research was supported by Marmara University, Scientific Research Projects – SAG-C-YLP-110915-0415 and SAG-E-120613-0233.Disclosure of interestThe authors have not supplied their declaration of competing interest.

2017 ◽  
Vol 41 (S1) ◽  
pp. S365-S366
Author(s):  
F. Aricioglu ◽  
T. Bastaskin ◽  
C. Kandemir ◽  
S. Sirvanci ◽  
C. Ozkartal ◽  
...  

ObjectivePurinergic 2X7 receptor (P2X7R) activation has recently been considered to be involved in depression at least partially by triggering microglial activation. The aim of the present study was to examine whether the chronic administration of brilliant blue G (BBG), a highly selective P2X7R antagonist, has antidepressant-like effects and microglial (Iba-1) immunoreactivity in chronic unpredictable mild stress (CUMS) model in rats.MethodsMale Wistar Albino rats (290–360 g) were divided into groups such as control (saline), CUMS, CUMS + Imipramine (20 mg/kg; i.p.), CUMS + BBG25 (25 mg/kg; i.p.), CUMS + BBG50 (50 mg/kg; i.p.) groups (n = 10–12 in each). In CUMS model, various stressors were applied for 40 days. On day 20, the treatment of BBG was started for 20 days. At the end, sucrose preference and forced swimming tests were performed. Then brains were removed with paraformaldehyde perfusion for Iba-1 immunohistochemical analysis in hippocampus. One-way analysis of variance and Tukey's test were used for statistical analysis.ResultsThe time of immobility in forced swim test was significantly reduced while sucrose preference was increased in Imipramine and CUMS + BBG50 groups compared to control and CUMS groups, respectively. In immunohistochemical experiments, Iba-1 was overexpressed in CUMS group and BBG significantly reduced the overexpression of Iba-1.ConclusionOur results suggest that chronic administration of BBG has an antidepressant-like activity supporting the notion of P2X7 receptors involvement in depression by modulating microglial activation.This research was supported by grant from Marmara University, Scientific Research Projects – SAG-C-YLP-110915-0416 and SAG-E-120613-0233.Disclosure of interestThe authors have not supplied their declaration of competing interest.


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.


Author(s):  
Vybhava Krishna ◽  
KL Bairy ◽  
Navin Patil ◽  
Sweenly V. Sunny

Abstract Background The 5HT4 receptor agonists are antidepressants with a unique mode of action. Many studies have been done on investigational drugs, and mosapride has been shown to have a 5HT3 antagonistic property. In this study, we assessed the potential anxiolytic and antidepressant effects of mosapride on Wistar albino rats. Methods The rats were randomly assigned to two models containing 4 groups of 6 animals each. In the anxiety model, four groups included 0.5 mL of 0.5% carboxymethyl cellulose (CMC), mosapride 1.5 mg/kg, mosapride 3 mg/kg and diazepam 2 mg/kg. They were dosed for 5 days. On the 3rd day, the elevated plus maze (EPM) was conducted, and on the 5th day, the open field (OF) tests were conducted. In the depression model, four groups included 0.5 mL of 0.5% CMC, mosapride 1.5 mg/kg, mosapride 3 mg/kg and imipramine 30 mg/kg. After 3 days of dosing, the forced swim test (FST) was conducted, followed by a washout period of 1 month. Then, the rats were subjected to chronic unpredictable stress with sucrose preference. Results Compared with the control, the mosapride-treated animals showed significant anxiolytic behavior at both high and low doses in the EPM and OF tests. In the FST, both high and low doses of mosapride reduced immobility. The climbing behavior was prominent at a high dose of mosapride, whereas swimming was prominent at a low dose. In the chronic stress model, both doses of mosapride preserved sucrose preference comparable to imipramine. Conclusion These findings suggest that mosapride has anxiolytic and antidepressant activities at clinically used doses.


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):  
Chaitra S. R. ◽  
Roopa P. Nayak ◽  
Uttara Krishna

Background: Depression is one of the common mental disorder prevalent worldwide. Use of herbal medicines in the treatment of depression is becoming popular because of adverse effects of existing non herbal drugs. In this study Psidium guajava leaf aqueous extract is screened for antidepressant activity in Wistar albino rats.Methods: Wistar albino rats of both sex were used. After performing acute toxicity study, dose of test drug was fixed to 100mg/kg and 200mg/kg. Test and standard drugs were administered for 10 days orally. Standard drug used was Imipramine. Antidepressant activity was assessed using forced swim test and tail suspension test.Results: Statistical analysis was done by one way ANOVA followed by Tukey Kramer. Aqueous extract of Psidium guajava leaves showed significant antidepressant activity. Both Psidium guajava aqueous extract (PGAE)-100mg/kg and 200mg/kg showed antidepressant effect but compared to 100mg/kg dose of PGAE, 200mg/kg showed significant antidepressant activity.Conclusions: From this study it can be concluded that aqueous extract of Psidium guajava leaves has antidepressant activity.


2021 ◽  
Author(s):  
Ankul Singh S ◽  
Gowri K ◽  
Chitra V

Abstract Nephrolithiasis appear to be a major health crisis among the population with serious medical related consequences throughout the lifetime of patient. The aim of the study was to evaluate the preventive effect of the hydro-alcoholic extract of A. lanata roots on Urolithiasis rats. Thirty adults male wistar Albino rats weighing 200 – 250 g were divided into five groups comprising 6 rats in each. Group I Served as positive control with water ad libitum. Group II as negative control which is disease treated group receiving 0.75% ethylene glycol mixed with drinking water for 28 days. Group III chosen as standard group receiving ethylene glycol for first 14 days and Cystone 750 mg/Kg from day 15 till day 28. Group IV and V received ethylene glycol for first 14 days and treatment regimen of LD (400 mg/Kg) and HD 800 mg/Kg orally from day 15 till day 28. Invitro studies like Nucleation, Aggregation and Growth assays were performed. Urine volume and pH was collected and observed for change in appearance, pH, odour and turbidity. Extract was given by preparing suspension and stability was observed by measuring its parameters. On Day 29, the kidneys were dissected and histopathology was done to check tubular injury. There was Increase in urine volume, enhanced excretion of urinary constituents like citrate, oxalate etc. and improving clearance rate. Improvement in pH and antioxidant activity was observed in treated groups. The extract showed that it has prominent effect on nephrolithiasis and has better safety profile in the dose given.


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.


Author(s):  
Youness Kadil ◽  
Imane Tabyaoui ◽  
Latifa Badre ◽  
Nadia Tahiri Jouti ◽  
Houda Filali

Background: Depression is a group of syndromes characterized by notable and persistent mood disorders, and is one of the most prevalent psychiatric disorders, while the existing treatments have an altered risk-benefit balance. The therapeutic properties of Nigella have been confirmed, suggesting the reliance on phytotherapy. The objective of the present paper is to investigate the antidepressive-like effect of Nigella sativa on rats exposed to the Unpredictable Chronic Mild Stress procedure. Methods: Wistar rats were used to investigate the antidepressive-like effect. The stress procedure used in this study combined many stressful conditions. After 6 weeks of treatment, behavioral test (forced swim test) was conducted, and histological changes of the hippocampus were examined. Results: Treatment by nigella and fluoxetine significantly reduced the struggling time. Conclusion: Histopathological analysis showed that control treatments result in more loosely arranged cells, significant apoptotic neurons characterized by an irregular appearance, and pyknotic hyperchromatic. A reduction of the thickness of the pyramid layer was also observed in the groups treated with nigella and fluoxetine, suggesting that nigella could be used as a treatment or an adjuvant preventing depressive-like disorders.


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.


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