β-1, 3-Glucan attenuated chronic unpredictable mild stress induced cognitive impairment in rodents via normalizing corticosterone levels

2020 ◽  
Vol 20 ◽  
Author(s):  
Saniya Hashim Khan ◽  
Sheraz Khan ◽  
Inamullah Khan ◽  
Narmeen Hashim
Keyword(s):  
Water Maze ◽  
Memory Impairment ◽  
Glucocorticoid Receptors ◽  
Therapeutic Potential ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Neuroprotective Effects ◽  
Injurious Effect ◽  
Naturally Occurring ◽  
Dose Dependent

Background: Chronic stress elevates the cortisol beyond normal levels, which affects cognition including learning & memory. This injurious effect is primarily mediated via over excitation of metabotropic glucocorticoid receptors (mGR). Methods: The present study was aimed appraise the neuroprotective effects of naturally occurring molecule β-1,3-glucan by interfering with stress-cortisol-mGR axis. Our data of virtual screening (in silico) exhibited the promising interactions of βglucan with the mGR. Therefore, the study was extended to evaluate its efficacy (2.5, 5 and 10 mg/kg/ i.p) in an animal model of chronic unpredictable mild stress (CUMS, 28 days) induced memory impairment. Results: Results of the current study revealed the β-glucan provided dose dependent protection against deleterious effects of stress on learning and memory associated parameters observed in Morris water maze (MWM) task. At higher tested doses, it has also significantly antagonized the stress induced weight loss and corticosterone elevation. Conclusion: From these findings, it can be deduced that the β-glucan possesses therapeutic potential against stress induced memory impairment, and this effect can be attributed to its normalizing effect on corticosterone levels.

scholarly journals Ginsenoside-Rg1 Rescues Stress-Induced Depression-Like Behaviors via Suppression of Oxidative Stress and Neural Inflammation in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Ye Li ◽  
Liyan Wang ◽  
Peng Wang ◽  
Cuiqin Fan ◽  
Ping Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Neuronal Damage ◽  
Present Report ◽  
Mild Stress ◽  
Ginsenoside Rg1 ◽  
Neuroprotective Effects ◽  
Related Condition ◽  
Antioxidant Stress

Depression is an inflammatory-related condition, with the progression in neuronal damage resulting in major depression disorder. Ginsenoside-Rg1, a sterol extract from the herb Panax ginseng, has been shown to exert neuroprotective effects upon neurodegeneration disorders. However, whether ginsenoside-Rg1 confers antidepressant-like effects on neuroinflammation as associated with depression, as well as the possible mechanism involved in these neuroprotective effects, is currently unclear. In the present report, we show that treatment with ginsenoside-Rg1 (40 mg/kg, i.p.) significantly ameliorated depressive-like behaviors as induced by chronic unpredictable mild stress (CUMS) in a rat model of depression. Moreover, these CUMS rats treated with ginsenoside-Rg1 showed reductions in the levels of the oxidative stress products and the activity in the antioxidant stress kinase. Furthermore, CUMS rats treated with ginsenoside-Rg1 showed ameliorated neuroinflammation and associated neuronal apoptosis along with a reduction in dendritic spine atrophy and display of depressive behaviors. Taken together, the results of this study suggest that ginsenoside-Rg1 produces antidepressant-like effects in CUMS-exposed rats; and one of the mechanisms for these antidepressant-like effects of ginsenoside-Rg1 appears to involve protection against oxidative stress and thus the neuronal deterioration resulting from inflammatory responses. These findings provide evidence for the therapeutic potential of ginsenoside-Rg1 in the treatment of stress-related depression.

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

Therapeutic potential of silymarin in chronic unpredictable mild stress induced depressive-like behavior in mice

2017 ◽  
Vol 32 (2) ◽  
pp. 223-235 ◽  
Author(s):  
Vishnu N Thakare ◽  
Rajesh R Patil ◽  
Rajesh J Oswal ◽  
Valmik D Dhakane ◽  
Manoj K Aswar ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress

scholarly journals Diosmetin Mitigates Cognitive and Memory Impairment Provoked by Chronic Unpredictable Mild Stress in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Elham Saghaei ◽  
Shakiba Nasiri Boroujeni ◽  
Parvin Safavi ◽  
Zeinab Borjian Boroujeni ◽  
Elham Bijad
Keyword(s):  
Object Recognition ◽  
Antioxidant Capacity ◽  
Chronic Stress ◽  
Memory Impairment ◽  
Control Group ◽  
Novel Object Recognition ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Novel Object ◽  
Serum Corticosterone

Background and Aim. Numerous reports have indicated that dealing with stressors in life is a main risk factor for the occurrence and progression of cognitive and memory impairment. Available treatments such as benzodiazepine and antidepressants address only certain aspects of this stress disorder and have numerous side effects. The present study was aimed at investigating the effect of diosmetin, as a flavonoid compound with potent antioxidant and anti-inflammatory effects, on cognitive impairment and chronic stress memory. Materials and Methods. In the present experimental study, male NMRI mice were exposed to chronic unpredictable mild stress (CUMS) paradigm for 35 days. Diosmetin (at doses of 10, 20, and 40 mg/kg. i.p.) or diosmetin solvent (normal saline + DMSO, 1 ml/kg; i.p.) was administered 30 min before stress induction. After 28 days, memory and cognitive performance were assessed by shuttle box and novel object recognition tests. Finally, antioxidant capacity (FRAP) and malondialdehyde (MDA) level of serum and brain, and serum corticosterone level were evaluated. Results. Behavioral tests showed that CUMS significantly reduced the secondary latency in passive avoidance memory test and diagnosis index in novel object recognition test compared to the control group ( P < 0.001 ), whereas treatment with diosmetin (20 and 40 mg/kg) significantly improved memory performance in the two tests ( P < 0.001 ). In addition, diosmetin (40 mg/kg) could pronouncedly suppress increase in serum corticosterone levels, reduction in antioxidant capacity, and production of excess MDA caused by CUMS compared to the control group ( P < 0.01 , P < 0.001 , and P < 0.001 , respectively). Conclusion. Chronic stress can impair memory and cognition and treatment with diosmetin can partly improve this disorder in male mice by increasing the antioxidant capacity of brain tissue and serum and improving serum corticosterone levels.

scholarly journals Allium hookeri Extracts Improve Scopolamine-Induced Cognitive Impairment via Activation of the Cholinergic System and Anti-Neuroinflammation in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2890
Author(s):  
Ji-Hye Choi ◽  
Eun-Byeol Lee ◽  
Hwan-Hee Jang ◽  
Youn-Soo Cha ◽  
Yong-Soon Park ◽  
...  
Keyword(s):  
Cholinergic System ◽  
Water Maze ◽  
Memory Impairment ◽  
Acetylcholinesterase Activity ◽  
Neuroprotective Effects ◽  
Root Extracts ◽  
Maze Test ◽  
Allium Hookeri ◽  
Y Maze ◽  
Acetylcholine Concentration

Allium hookeri (AH) is a medicinal food that has been used in Southeast Asia for various physiological activities. The objective of this study was to investigate the activation of the cholinergic system and the anti-neuroinflammation effects of AH on scopolamine-induced memory impairment in mice. Scopolamine (1 mg/kg body weight, i.p.) impaired the performance of the mice on the Y-maze test, passive avoidance test, and water maze test. However, the number of error actions was reduced in the AH groups supplemented with leaf and root extracts from AH. AH treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. AH significantly improved the cholinergic system by decreasing acetylcholinesterase activity, and increasing acetylcholine concentration. The serum inflammatory cytokines (IL-1β, IL-6, and IFN-γ) increased by scopolamine treatment were regulated by the administration of AH extracts. Overexpression of NF-κB signaling and cytokines in liver tissue due to scopolamine were controlled by administration of AH extracts. AH also significantly decreased Aβ and caspase-3 expression but increased NeuN and ChAT. The results suggest that AH extracts improve cognitive effects, and the root extracts are more effective in relieving the scopolamine-induced memory impairment. They have neuroprotective effects and reduce the development of neuroinflammation.

scholarly journals Ginsenoside Rg1 Prevents Chronic Stress-Induced Depression-Like Behaviors and Neuronal Structural Plasticity in Rats

2018 ◽  
Vol 48 (6) ◽  
pp. 2470-2482 ◽  
Author(s):  
Hongluan Yu ◽  
Cuiqin Fan ◽  
Lejin Yang ◽  
Shuyan Yu ◽  
Qiqi Song ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Rat Model ◽  
Basolateral Amygdala ◽  
Therapeutic Potential ◽  
Chronic Administration ◽  
Ultrastructural Changes ◽  
Mild Stress ◽  
Ginsenoside Rg1 ◽  
Neuroprotective Effects ◽  
Neuronal Mechanisms

Background/Aims: Ginsenoside Rg1 has been demonstrated to exhibit neuroprotective effects in various studies. This study aimed to investigate the neuronal mechanisms underlying the neuroprotective and antidepressant-like effects of ginsenoside Rg1 in a rat model of depression. Methods: Chronic unpredictable mild stress was used to induce depression-like behaviors in rats. Transmission electron microscopy was used to observe neuronal synapses within the basolateral amygdala (BLA). The expression of microRNA (miR)-134 in the BLA was verified by real-time quantitative PCR. Finally, the synaptic plasticity-associated proteins CAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were detected by immunoblotting. Results: Results showed that chronic stress effectively induced depression-like behaviors in rats, which were associated with significant ultrastructural changes within BLA neurons. Moreover, chronic stress decreased the expression of miR-134 in the BLA, which was accompanied by decreased phosphorylation of CREB and decreased expression of BDNF. Remarkably, chronic administration of ginsenoside Rg1 (40 mg/kg, i.p., 5 weeks) significantly ameliorated the neuronal structural abnormalities and biochemical changes induced by chronic stress, as well as preventing depression-like behaviors in these rats. Conclusion: Results suggested that ginsenoside Rg1 may exhibit neuroprotection and antidepressant-like effects by activating the CREB-BDNF system within the BLA in this rat model of depression. Amelioration of depression-like behaviors by ginsenoside Rg1 appears to involve modulation of the synapse-associated factor miR-134 within the BLA. Therefore, these findings demonstrate some of the neuronal mechanisms associated with depression and the therapeutic potential of ginsenoside Rg1 for use in the treatment of depression in clinical trials.

The neuroprotective effects of flupirtine and beta-amyloid induced memory impairment

2011 ◽  
Author(s):  
Matthew Jefferson ◽  
Sara Smeltzer ◽  
Jeffery L. McMillin ◽  
Caitlin C. Henry ◽  
Brittney M. Klauser ◽  
...  
Keyword(s):  
Memory Impairment ◽  
Beta Amyloid ◽  
Neuroprotective Effects

Anticoagulant Activity of Hirulog™, a Direct Thrombin Inhibitor, in Humans

1993 ◽  
Vol 69 (02) ◽  
pp. 157-163 ◽  
Author(s):  
Irving Fox ◽  
Adrian Dawson ◽  
Peter Loynds ◽  
Jane Eisner ◽  
Kathleen Findlen ◽  
...  
Keyword(s):  
Rational Design ◽  
Therapeutic Potential ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
Direct Thrombin Inhibitor ◽  
Controlled Study ◽  
Thrombin Inhibitor ◽  
Thrombin Time ◽  
Thrombotic Disease ◽  
Dose Dependent

SummaryHirulog™ (BG8967) is a direct thrombin inhibitor built by rational design using the protein hirudin as a model (Maraganore et al. [1990]; Biochemistry 29: 7095–101). In order to evaluate the therapeutic potential for hirulog in the management of thrombotic disease, the tolerability and anticoagulant activity of the agent were examined in a study of human volunteers.In a randomized, placebo-controlled study (n = 54), the intravenous infusion of hirulog over 15 min showed a rapid, dose-dependent prolongation of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). There was a corresponding dose-dependent increase in plasma hirulog levels. The peptide was rapidly cleared with a half-life of 36 min and a total body clearance rate for the peptide of 0.43 1 kg−1 h−1. Similar activity was observed following subcutaneous injection but with sustained pharmacodynamic and pharmacokinetic behavior. There was a significant correlation between pharmacokinetic and pharmacodynamic variables for both intravenous (r = 0.8, p <0.001) and subcutaneous administration (r = 0.7, p = 0.002).To evaluate the possible interactions of aspirin on the tolerability and anticoagulant activity of intravenous hirulog, a cross-over design was employed in eight subjects. Aspirin administration did not modify the peptide’s activity. At the administered dose of 0.6 mg kg−1 h−1 for 2 h, hirulog infusion prolonged APTT from 230 to 260% baseline. The infusion of hirulog in subjects who had received aspirin was not associated with any significant changes in the template bleeding time.The final phase of the study examined the activity and tolerability of hirulog in ten subjects during prolonged intravenous infusions for up to 24 h. The peptide (0.3 mg kg−1 h−1) exhibited sustained anticoagulant activity with no evidence for a cumulative effect. During hirulog infusion, APTT was prolonged from 210 to 250% baseline.In all phases of the study, hirulog administration was generally well-tolerated.Our observations show that hirulog is an active antithrombin agent with excellent tolerability in humans. As a direct thrombin inhibitor, hirulog provides a novel approach for the management of thrombotic disease.

Sign in / Sign up

Export Citation Format

Share Document