scholarly journals Xiaoyao Pills Ameliorate Depression-like Behaviors and Oxidative Stress Induced by Olfactory Bulbectomy in Rats via the Activation of the PIK3CA-AKT1-NFE2L2/BDNF Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yafei Ji ◽  
Jie Luo ◽  
Jiuseng Zeng ◽  
Yang Fang ◽  
Rong Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Preference Test ◽  
Sucrose Preference ◽  
Neuroprotective Effects ◽  
Antidepressant Effects ◽  
Mrna And Protein Expression ◽  
Bdnf Signaling ◽  
Sucrose Preference Test ◽  
Reduced Activity ◽  
And Oxidative Stress

Numerous studies have revealed that oxidative stress is closely associated with the occurrence and development of depression. Xiaoyao Pills (XYW) are included in the Chinese Pharmacopoeia and are frequently used for treating anxiety and depression by smoothing the liver, strengthening the spleen, and nourishing the blood. However, the antidepressant effects of XYW have not yet been thoroughly investigated. The objective of our study was to investigate the antidepressant-like effects of XYW and the underlying molecular mechanism in the olfactory bulbectomized (OB) rat model of depression using the open field test (OFT), sucrose preference test (SPT), splash test (ST), and novelty suppressed feeding test (NSFT). Results showed that XYW (0.93 and 1.86 g·kg−1) significantly alleviated depression-like behaviors in rats, which was indicated by increased sucrose preference in the SPT, prolonged grooming time in the ST, decreased horizontal movement in the OFT, and shorter feeding latency in the NSFT. In addition, XYW treatment dramatically reversed the reduced activity of superoxide dismutase and the decreased level of glutathione, while also lowering levels of malondialdehyde, an inflammatory mediator (nitric oxide), and pro-inflammatory cytokines (interleukin-6 and 1β) in the serum and cortex of OB rats. Mechanistically, XYW induced marked upregulation of mRNA and protein expression levels of NFE2L2, KEAP1, GPX3, HMOX1, SOD1, NQO1, OGG1, PIK3CA, p-AKT1/AKT1, NTRK2, and BDNF, and downregulation of ROS in the cortex and hippocampus via the activation of the NFE2L2/KEAP1, PIK3CA/AKT1, and NTRK2/BDNF pathways. These findings suggest that XYW exert antidepressant-like effects in OB rats with depression-like symptoms, and these effects are mediated by the alleviation of oxidative stress and the enhancement of neuroprotective effects through the activation of the PIK3CA-AKT1-NFE2L2/BDNF signaling pathways.

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 Sulfoquinovosyl oleoyl palmitoyl glycerol (SQDG) and hexane extract of Sargassum plagyophylum prevent depression induced by dexamethasone or stress in mice

2021 ◽  
Vol 10 (2) ◽  
pp. 262-268
Author(s):  
Afsaneh Yegdaneh ◽  
Azadeh Mesripour ◽  
Marjan Keyvani
Keyword(s):  
Preference Test ◽  
Hexane Extract ◽  
Sucrose Preference ◽  
Clinical Evaluations ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Swimming Test ◽  
Isolated Compound ◽  
Sucrose Preference Test ◽  
Palmitoyl Glycerol

Introduction: M Glucocorticoids and stress are a leading cause of depression by dysregulation of hypothalamic hypophyseal adrenal axis. Sargassum plagyophylum hexane extract (HxE) has proven antidepressant-like effects in mice. We aimed at evaluating HxE and sulfoquinovosyl oleoyl palmitoyl glycerol (SQDG) isolated compound antidepressant effects following dexamethasone (Dex) or water avoidance stress (WAS) induced depression in mice. Methods: The HxE was prepared and fractionated by different chromatography methods to isolate active compounds. Depression was induced in male mice by Dex single dose or by four days of WAS. After the locomotor test, depression was assessed by measuring the immobility time during the forced swimming test (FST) and sucrose preference test. Results: 6-Deoxy-6-sulpho-α-D-glucopyranosyl-1,2-O-diacyl-glycerol was isolated and elucidated from the seaweed. The manipulations did not cause important changes in animals’ locomotor activity. During FST, immobility time increased dramatically by Dex (193 ± 13 s vs control 109 ± 7 s) or WAS (189 ± 13 s vs sham 86 ± 14 s), that indicated depression. HxE 40 mg/kg reduced the immobility time when it was administered with Dex (110 ± 28 s, P < 0.01 vs Dex alone) or together with WAS (86 ± 11 s, P < 0.001 vs WAS). SQDG 40 mg/kg reduced the immobility time when co-administered with Dex (22 ± 9 s, P < 0.001 vs Dex alone) and when it was administered along with WAS (68 ± 16 s, P < 0.001 vs WAS). The results of the sucrose preference test were in line with FST results as sucrose preference below 65% was considered for anhedonia. Conclusion: SQDG and probably the steroid content in S. plagyophylum HxE prevented depression in mice; thus, they should be considered for further clinical evaluations.

scholarly journals Neuroprotective Effects of Grape Seed Procyanidins on Ethanol-Induced Injury and Oxidative Stress in Rat Hippocampal Neurons

2020 ◽  
Vol 55 (4) ◽  
pp. 357-366
Author(s):  
Wenyang Jin ◽  
Mizhu Sun ◽  
Bingbing Yuan ◽  
Runzhi Wang ◽  
Hongtao Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hippocampal Neurons ◽  
Primary Cultures ◽  
Neuronal Injury ◽  
Grape Seed ◽  
Neuroprotective Effects ◽  
Dendritic Length ◽  
New Type ◽  
The Brain ◽  
And Oxidative Stress

Abstract Aims Ethanol is a small molecule capable of interacting with numerous targets in the brain, the mechanisms of which are complex and still poorly understood. Studies have revealed that ethanol-induced hippocampal neuronal injury is associated with oxidative stress. Grape seed procyanidin (GSP) is a new type of antioxidant that is believed to scavenge free radicals and be anti-inflammatory. This study evaluated the ability and mechanism by which the GSP improves ethanol-induced hippocampal neuronal injury. Methods Primary cultures of hippocampal neurons were exposed to ethanol (11, 33 and 66 mM, 1, 4, 8, 12 and 24 h) and the neuroprotective effects of GSP were assessed by evaluating the activity of superoxide dismutase (SOD), the levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) and cell morphology. Results Our results indicated that GSP prevented ethanol-induced neuronal injury by reducing the levels of MDA and LDH, while increasing the activity of SOD. In addition, GSP increased the number of primary dendrites and total dendritic length per cell. Conclusion Together with previous findings, these results lend further support to the significance of developing GSP as a therapeutic tool for use in the treatment of alcohol use disorders.

scholarly journals Neuroprotective effects of Withania somnifera in BPA induced-cognitive dysfunction and oxidative stress in mice

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Hareram Birla ◽  
Chetan Keswani ◽  
Sachchida Nand Rai ◽  
Saumitra Sen Singh ◽  
Walia Zahra ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Dysfunction ◽  
Withania Somnifera ◽  
Neuroprotective Effects ◽  
And Oxidative Stress

scholarly journals Benzimidazole Containing Acetamide Derivatives Attenuate Neuroinflammation and Oxidative Stress in Ethanol-Induced Neurodegeneration

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 108 ◽  
Author(s):  
Muhammad Imran ◽  
Lina Tariq Al Kury ◽  
Humaira Nadeem ◽  
Fawad Ali Shah ◽  
Muzaffar Abbas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Calcium Binding ◽  
Nuclear Factor Κb ◽  
Single Step ◽  
Ethanol Administration ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neuroprotective Effects ◽  
Neuroprotective Strategy ◽  
And Oxidative Stress

Oxidative stress-induced neuroinflammation is the prominent feature of neurodegenerative disorders, and is characterized by a gradual decline of structure and function of neurons. Many biochemical events emerge thanks to the result of this neurodegeneration, and ultimately provoke neuroinflammation, activation of microglia, and oxidative stress, leading to neuronal death. This cascade not only explains the complexity of events taking place across different stages, but also depicts the need for more effective therapeutic agents. The present study was designed to investigate the neuroprotective effects of newly synthesized benzimidazole containing acetamide derivatives, 3a (2-(4-methoxyanilino)-N-[1-(4-methylbenzene-1-sulfonyl)-1H-benzimidazol-2-yl] acetamide) and 3b (2-(Dodecylamino)-N-[1-(4-methylbenzene-1-sulfonyl)-1H-benzimidazol-2-yl] acetamide) against ethanol-induced neurodegeneration in the rat model. Both derivatives were characterized spectroscopically by proton NMR (1H-NMR) and carbon-13 NMR (13C-NMR) and evaluated for neuroprotective potential using different pharmacological approaches. In vivo experiments demonstrated that ethanol triggered neurodegeneration characterized by impaired antioxidant enzymes and elevated oxidative stress. Furthermore, ethanol administration induced neuroinflammation, as demonstrated by elevated expression of tumor necrotic factor (TNF-α), nuclear factor κB (NF-κB), cyclooxygenase-2 (COX2), and ionized calcium-binding adapter molecule-1 (Iba-1), which was further validated by enzyme-linked immunosorbent assay (ELISA). Treatment with 3a and 3b ameliorated the ethanol-induced oxidative stress, neuroinflammation, and memory impairment. The affinity of synthesized derivatives towards various receptors involved in neurodegeneration was assessed through docking analysis. The versatile nature of benzimidazole nucleus and its affinity toward several receptors suggested that it could be a multistep targeting neuroprotectant. As repetitive clinical trials of neuroprotectants targeting a single step of the pathological process have failed previously, our results suggested that a neuroprotective strategy of acting at different stages may be more advantageous to intervene in the vicious cycles of neuroinflammation.

Lipopolysaccharide-Induced Depression-Like Behaviors Is Ameliorated by Sodium Butyrate via Inhibiting Neuroinflammation and Oxido-Nitrosative Stress

Pharmacology ◽  
2020 ◽  
Vol 105 (9-10) ◽  
pp. 550-560
Author(s):  
Jian Qiu ◽  
Renjie Liu ◽  
Yaoying Ma ◽  
Yan Li ◽  
Zhuo Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prefrontal Cortex ◽  
Sodium Butyrate ◽  
Nitrosative Stress ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Common Disease ◽  
Neuroinflammatory Response ◽  
Models Of Disease ◽  
And Oxidative Stress

Depression is a common disease that afflicts one in 6 people. Numerous hypotheses have been raised in the past decades, but the exact mechanism for depression onset remains obscure. Recently, the neuroinflammatory response and oxidative stress are being attracted more and more attention due to their roles in depression pathogenesis. The inhibition of neuroinflammatory response and oxidative stress is now considered a potential strategy for depression prevention and/or therapy. Sodium butyrate (SB) is a sodium form of the endogenous butyrate. It can inhibit proinflammatory responses and oxidative stress in different models of disease. In the present study, we investigated the effect of SB on lipopolysaccharide (LPS)-induced depression-like behaviors, neuroinflammatory response, and oxido-nitrosative stress in the hippocampus and prefrontal cortex in C57BL6/J mice. Our results showed that 10 days of SB pretreatment at the dose of 300 but not 100 mg/kg markedly ameliorated LPS (0.83 mg/kg)-induced depression-like behaviors in the tail suspension test, forced swimming test, and sucrose preference test. Further analysis showed that 10 days of SB pretreatment not only prevented LPS-induced increases in proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, in the hippocampus and prefrontal cortex but also prevented LPS-induced enhancement of oxido-nitrosative stress. Taken together, these results demonstrate that SB is such an agent that could be used to prevent depression onset and/or progression, and inhibition of neuroinflammatory response and oxido-nitrosative stress may be a potential mechanism for its antidepressant actions.

Benefit Agmatine Effects in Experimental Multiple Sclerosis. CNS Nitrosative and Oxidative Stress Suppression / Protektivni Efekti Agmatina U Eksperimentalnoj Multiploj Sklerozi. Supresija Nitrozativnog I Oksidativnog Stresa U CNS-U

2014 ◽  
Vol 31 (4) ◽  
pp. 233-243
Author(s):  
Ivana Stojanović ◽  
Srđan Ljubisavljević ◽  
Ivana Stevanović ◽  
Slavica Stojnev ◽  
Radmila Pavlović ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Clinical Symptoms ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Autoimmune Encephalomyelitis ◽  
Sod Activity ◽  
Neuroprotective Effects ◽  
Sprague Dawley Rats ◽  
And Oxidative Stress

Summary The aim of this study was to investigate the exogenous agmatine influence on nitrosative and oxidative stress parameters in acute phase of multiple sclerosis (MS) experimental model, experimental autoimmune encephalomyelitis (EAE). EAE was induced by subcutaneous injection of myelin basic protein (50 μg per animal). Sprague-Dawley rats were divided into five groups: I group - (CG), treated by PBS (i.p.), II group - (EAE), III group - (CFA), treated with Complete Freund’s adjuvant (0.2 ml subcutaneously), IV group - (EAE+AGM), treated by agmatine (75 mg/kg bw i.p.) upon EAE induction and V group - (AGM), received only agmatine in the same dose. The animals were treated every day during experiment - from day 0 to 15, and clinically scored every day. They were sacrificed on day 16 from MBP application. NO2+NO3, S-nitrosothiols (RSNO), malondyaldehide (MDA) and reduced glutathione (GSH) concentrations and superoxide dismutase (SOD) activity were determined in rat whole encephalitic mass (WEM) and cerebellum homogenates. Agmatine exerted strong protective effects on EAE clinical symptoms (p<0.05). In EAE brain homogenates, NO2+NO3, RSNO and MDA concentrations were increased compared to CG values. Agmatine treatment diminished NO2+NO3, RSNO and MDA levels in EAE animals (p<0.05). In EAE rats, GSH level and SOD activity were decreased compared to CG values, but agmatine treatment increased both parameters compared to EAE untreated animals (p<0.05). Immunohistochemical staining supported the clinical and biochemical findings in all groups. The CNS changes in EAE are successfully supressed by agmatine application, which could be the the new aspect of the neuroprotective effects of agmatine.

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