scholarly journals Hericium erinaceus mycelium ameliorate anxiety induced by continuous sleep disturbance in vivo

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tsung-Ju Li ◽  
Tung-Yen Lee ◽  
Yun Lo ◽  
Li-Ya Lee ◽  
I-Chen Li ◽  
...  
Keyword(s):  
Sleep Disturbance ◽  
Elevated Plus Maze ◽  
Large Body ◽  
Light Period ◽  
Sleep Disruption ◽  
Public Health Issue ◽  
Dual Function ◽  
Hericium Erinaceus ◽  
Plus Maze

Abstract Background Sleep disruption is a major public health issue and may increase the risk of mortality by ten-folds if an individual is sleeping less than 6 h per night. Sleep has changed dramatically during to the COVID-19 pandemic because COVID symptoms can lead to psychological distress including anxiety. Hericium erinaceus mycelium has been widely investigated in both the in vivo studies and clinical trials for its neuroprotective functions because the mycelium contains hericenones and erinacines, which synthesize the nerve growth factor and brain-derived neurotrophic factor (BDNF). Recent in vivo reports have shown showed that erinacine A-enriched Hericium erinaceus mycelium can modulate BDNF/TrkB/PI3K/Akt/GSK-3β pathways to induce an antidepressant-like effect. A large body of evidence indicates that erinacine can pass the blood-brain barrier and suggests its neuroprotective function in both peripheral and central nervous systems. Thus, Hericium erinaceus mycelium may be a dual-function supplement for sleep disruption improvement while sustaining anxiolytic effects. Method To simulate the condition of sleep disruption, the mice were subjected to the tail suspension test (TST) for 15 min every day during the same period for nine consecutive days. Two different doses (75 and 150 mg/kg) of Hericium erinaceus mycelium were administered orally 20 min prior to the TSTs before entering the light period of 12:12 h L:D cycle. All sleep-wake recording was recorded for 24 h using electroencephalogram and electromyogram. The elevated-plus-maze and open-field tests were conducted to record the behavior activities. Results Consecutive TSTs prior to the light period could cause significant sleep disturbance and anxiety behavior in the elevated-plus-maze experiments. Results showed that administration with Hericium erinaceus mycelium at 150 mg/kg ameliorated the rodent anxiety (p < 0.05) and reversed the TST-induced NREM sleep disturbance in the dark period. Conclusion This is the first in vivo study suggesting that Hericium erinaceus mycelium has a dual potential role for anxiety relief through improving sleep disruptions.

scholarly journals Solitary Nitric Oxide Signaling Mediates Mild Stress-Induced Anxiety and Norepinephrine Release in the Bed Nucleus of the Stria Terminalis during Protracted Ethanol Withdrawal

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zhenglin Zhao ◽  
Sang Chan Kim ◽  
Yu Jiao ◽  
Yefu Wang ◽  
Bong Hyo Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Elevated Plus Maze ◽  
In Vivo Microdialysis ◽  
Ethanol Withdrawal ◽  
Mild Stress ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Nitric Oxide Signaling ◽  
Plus Maze

Ethanol withdrawal (EtOHW) alters the pattern of neurohormonal and behavioral response toward internal and external stimuli, which mediates relapse to alcohol use even after a long period of abstinence. Increased noradrenergic signaling from the nucleus tractus solitarius (NTS) to the bed nucleus of the stria terminalis (BNST) during EtOHW underlies withdrawal-induced anxiety, while nitric oxide synthase (NOS) inhibitors injected into the periaqueductal area attenuate EtOHW-induced anxiety. Therefore, this study investigated the involvement of NOS within the NTS in anxiety and increased norepinephrine (NE) release in the BNST during protracted EtOHW in rats exposed to a mild stress. Rats were intraperitoneally administered 3 g/kg/day EtOH for 21 days followed by 28 days of withdrawal, and on the 28th day of withdrawal, the rats were subjected to restraint stress for 7 minutes. The elevated plus maze test was employed to evaluate anxiety-like behavior in rats, and in vivo microdialysis was used to measure the extracellular NE level in the BNST. In elevated plus maze tests, EtOHW rats but not EtOH-naive rats exhibited anxiety-like behavior when challenged with 7-minute mild restraint stress, which was, respectively, mitigated by prior intra-NTS infusion of the nitric oxide scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), nonselective NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), or selective neuronal NOS (nNOS) inhibitor 7-nitroindazole (7-NI). Each of these agents also decreased the plasma corticosterone levels in EtOHW rats. In in vivo microdialysis, prior intra-NTS infusion of carboxy-PTIO, L-NAME, or 7-NI attenuated the mild stress-induced NE release in the BNST of EtOHW rats. Additionally, EtOHW rats showed increased solitary nNOS gene and protein expression. Moreover, the anxiolytic effect of intra-NTS administration of 7-NI was abolished by subsequent intra-NTS administration of sodium nitroprusside. These results suggest that elevation of solitary nitric oxide signaling derived from nNOS mediates stress-precipitated anxiety and norepinephrine release in the BNST during protracted EtOHW.

scholarly journals CARBAMAZEPINE LOADED VESICULAR STRUCTURES FOR ENHANCED BRAIN TARGETING VIA INTRANASAL ROUTE: OPTIMIZATION, IN VITRO EVALUATION, AND IN VIVO STUDY

2019 ◽  
pp. 264-274 ◽  
Author(s):  
GHADA E. YASSIN ◽  
REHAM I. AMER ◽  
AHMED M. FAYEZ
Keyword(s):  
Elevated Plus Maze ◽  
Physical Stability ◽  
Intranasal Route ◽  
Vesicular Structure ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Plus Maze ◽  
The Brain

Objective: Carbamazepine (CBZ) is used as a first line in the treatment of grand mal and partial seizures, but it suffers from many side effects on different systems of the body. The objective of the present study was optimization of CBZ vesicular structures using 23 multifactorial design for the most efficient targeting of CBZ to the brain via the intranasal route. Methods: The concentration of CBZ (10 and 20%), type of vesicles (niosomes and spanlastics) and speed of rotation (200 and 300 rpm) were considered as the independent variables XA, XB and XC respectively, while the dependent variables were particle size PS (Y1), polydispersity index PDI (Y2), zeta potential ZP (Y3) and entrapment efficiency EE (Y4). The study of the effect of different formulation variables was carried out using Design-Expert ® software. CBZ-loaded spanlastics and noisome were prepared by the ethanol injection method and thin film hydration method, respectively. The optimized formulation was subjected to viscosity measurement, in vitro drug release and physical stability studies. In vivo evaluations in rats for the optimized formulation in comparison to oral CBZ suspension was carried out using behavioral assessment by elevated plus maze test, determination of endothelial nitric oxide synthase (e-NOS), reduced glutathione (GSH) and ELISA estimation of TNFα. Results: The selected optimized formulation (F0) containing 20% CBZ and spanlastic vesicular structure showed PS, PDI, ZP, and the EE % of 350.09 nm, 0.830, 16.124mV and 82.777%, respectively. In vitro release study of F0 demonstrated the ability of the F0 to increase drug release in the range time from 10-60 min (p<0.05) when compared with CBZ suspension. The viscosity of F0 was nearly uniform (65 cps). The photomicrograph taken by the transmission electron microscopy (TEM) reveals the spherical shape of F0. Good physical stability for six months of storage at 25˚ C was found for F0. The optimized spanlastic formulation F0 showed a decrease in latency time in behavior assessment test using elevated plus Maze test, a decrease in serum eNOS and TNF-α and increase in GSH when compared with the oral CBZ suspension, in addition to the histopathological study that revealed the more CBZ uptake by the brain. Conclusion: The optimized spanlastic formulation F0 achieved better results when compared with the oral CBZ suspension for targeting the CBZ spanlastics vesicular structure to the brain via the nasal route.

scholarly journals Evaluation of the neuroprotective activity of a new allylmorpholine derivative in a rat model of traumatic brain injury

2021 ◽  
Vol 10 (4) ◽  
pp. 179-187
Author(s):  
V. A. Prikhodko ◽  
A. V. Kan ◽  
Yu. I. Sysoev ◽  
I. A. Titovich ◽  
N. A. Anisimova ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rat Model ◽  
Neurological Deficit ◽  
Elevated Plus Maze ◽  
Neuroprotective Activity ◽  
Drug Candidates ◽  
Plus Maze

Introduction. The search for and development of new drugs capable of reducing the severity of neurological deficit in traumatic brain injury are a critical task for investigational pharmacology. Chromone-containing allylmorpholines are a new group of neuroprotective drug candidates that have been shown to inhibit acetylcholinesterase and butyrylcholinesterase, and block N-methyl-D-aspartate receptors in vitro.Aim. This study aimed to evaluate the neuroprotective activity of the allylmorpholine derivative (E)-4-[3-(8-bromo-6-methyl-4-oxo-4H-chromen- 3-yl)-1-cyclohexylallyl]morpholin-4-ium chloride (33b) in vivo using a rat model of traumatic brain injury.Materials and methods. Traumatic brain injury was induced using the controlled cortical impact model. The allylmorpholine derivative was administered intraperitoneally at 1, 10, or 50 mg × kg-1 b.w. at 1 h after trauma induction, and then daily for the next 6 d. The neurological deficit was assessed using the Limb Placing, Open Field, Elevated Plus Maze, Beam Walking, and Cylinder tests.Results and discussion. At all doses administered, the allylmorpholine derivative had no positive effect on the motor function or exploratory behavior following traumatic brain injury. In the Elevated Plus Maze, 10 mg × kg-1 b.w. of the compound further suppressed exploratory behaviour in the injured animals, which appears to be consistent with its sedative properties observed previously in zebrafish.Conclusion. Despite the previously described in vitro affinity of allylmorpholines towards several molecular targets crucial for the pathogenesis of brain trauma and posttraumatic functional recovery, an allylmorpholine derivative had no neuroprotective effect in a rat model of traumatic brain injury in this study. These results further emphasize the importance of in vivo evaluation of potential neuroprotective drug candidates.

scholarly journals Involvement of GABAA Receptors in the Anxiolytic-Like Effect of Hydroxycitronellal

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Jéssica C. Andrade ◽  
Álefe B. Monteiro ◽  
Humberto H. N. Andrade ◽  
Thallita K. S. N. Gonzaga ◽  
Pablo R. Silva ◽  
...  
Keyword(s):  
Open Field ◽  
Mechanism Of Action ◽  
Gabaa Receptors ◽  
In Silico ◽  
Elevated Plus Maze ◽  
Field Tests ◽  
Plus Maze ◽  
In Silico Studies ◽  
Sedative Effects

Hydroxycitronellal (HC) is a monoterpene present in essential oils of aromatic plants of different species, obtained from semisynthesis of citronellal, and is widely used as a fragrance in cosmetics. The objective of this work was to evaluate the possible anxiolytic-like activity of HC and its possible mechanism of action using in vivo and in silico methodologies. Swiss male mice (Mus musculus) were treated with HC (12.5, 25, and 50 mg/kg, i.p.) and subjected to the rota rod, elevated plus maze, and open field tests. No significant impairments were observed in the rota rod tests for the motor activity of the animals treated with HC at 12.5, 25, and 50 mg/kg, i.p., indicating no myo-relaxing or sedative effects. In the elevated plus maze, HC (in the three doses) induced significant increases in the percentage of entries (respectively, 34.8%, 33.8%, and 38.6%) and in the length of stay (respectively, 49.9%, 56.1%, and 57.0%) in the open arms of the EPM, as well as the number of crossings in the open field tests. The mechanism of action of the compound’s anxiolytic-like activity can be attributed to the involvement of GABAA receptors, and this interaction was observed in in vivo and in silico studies. For HC, the results suggest anxiolytic-like effects, possibly via modulation of the GABAergic system. The use of natural products to treat anxiety can become an alternative to existing synthetic products.

scholarly journals N-(2-Hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1H- benzimidazol-1-yl)propyl]piperidine-4-Carboxamide (D2AAK4), a Multi-Target Ligand of Aminergic GPCRs, as a Potential Antipsychotic

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 349
Author(s):  
Agnieszka A. Kaczor ◽  
Katarzyna M. Targowska-Duda ◽  
Andrea G. Silva ◽  
Magda Kondej ◽  
Grażyna Biała ◽  
...  
Keyword(s):  
Memory Consolidation ◽  
Elevated Plus Maze ◽  
G Protein Coupled Receptors ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Antipsychotic Activity ◽  
Plus Maze ◽  
G Protein Coupled

N-(2-hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1H-benzimidazol -1-yl)propyl]piperidine-4-carboxamide (D2AAK4) is a multitarget ligand of aminergic G protein-coupled receptors (GPCRs) identified in structure-based virtual screening. Here we present detailed in vitro, in silico and in vivo investigations of this virtual hit. D2AAK4 has an atypical antipsychotic profile and low affinity to off-targets. It interacts with aminergic GPCRs, forming an electrostatic interaction between its protonatable nitrogen atom and the conserved Asp 3.32 of the receptors. At the dose of 100 mg/kg D2AAK4 decreases amphetamine-induced hyperactivity predictive of antipsychotic activity, improves memory consolidation in passive avoidance test and has anxiogenic properties in elevated plus maze test (EPM). Further optimization of the virtual hit D2AAK4 will be aimed to balance its multitarget profile and to obtain analogs with anxiolytic activity.

scholarly journals Investigation of the Pharmacological Properties of Lepidagathis hyalina Nees through Experimental Approaches

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 180
Author(s):  
Fowzul Islam Fahad ◽  
Niloy Barua ◽  
Md. Shafiqul Islam ◽  
Syed Al Jawad Sayem ◽  
Koushik Barua ◽  
...  
Keyword(s):  
Forced Swimming Test ◽  
Elevated Plus Maze ◽  
Tail Suspension Test ◽  
Clot Lysis ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Plus Maze ◽  
Swimming Test ◽  
Dose Dependent

Lepidagathis hyalina Nees is used locally in Ayurvedic medicine to treat coughs and cardiovascular diseases. This study explored its pharmacological potential through in vivo and in vitro approaches for the metabolites extracted (methanolic) from the stems of L. hyalina. A qualitative phytochemical analysis revealed the presence of numerous secondary metabolites. The methanol extract of L. hyalina stems (MELHS) showed a strong antioxidative activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and reducing power assays, and in the quantitative (phenolic and flavonoid) assay. Clot lysis and brine shrimp lethality bioassays were applied to investigate the thrombolytic and cytotoxic activities, respectively. MELHS exhibited an expressive percentage of clot lysis (33.98%) with a moderately toxic (115.11 μg/mL) effect. The in vivo anxiolytic activity was studied by an elevated plus maze test, whereas the antidepressant activity was examined by a tail suspension test and forced swimming test. During the anxiolytic evaluation, MELHS exhibited a significant dose-dependent reduction of anxiety, in which the 400 mg/kg dose of the extract showed 78.77 ± 4.42% time spent in the open arm in the elevated plus maze test. In addition, MELHS demonstrated dose-dependent and significant activities in the tail suspension test and forced swimming test, whereas the 400 mg/kg dose of the extract showed 87.67 ± 6.40% and 83.33 ± 6.39% inhibition of immobile time, respectively. Therefore, the current study suggests that L. hyalina could be a potential source of anti-oxidative, cytotoxic, thrombolytic, anxiolytic, and antidepressant agents. Further study is needed to determine the mechanism behind the bioactivities.

scholarly journals In-vivo and in-vitro evaluation of pharmacological activities of Ardisia solanacea leaf extract

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Mohammad Rashedul Islam ◽  
Jannatul Naima ◽  
Nawreen Monir Proma ◽  
Md. Saddam Hussain ◽  
S. M. Naim Uddin ◽  
...  
Keyword(s):  
Body Weight ◽  
Leaf Extract ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Immersion Method ◽  
Plus Maze ◽  
Tail Immersion ◽  
Hole Board

Abstract Background The Bangladeshi rural and hilly areas people have long tradition to use various medicinal plants for treating different diseases. That’s why, the crude methanolic leaf extract of Ardisia solanacea with its different fractions (petroleum ether, carbon tetrachloride, n-hexane and chloroform fractions) were subjected to investigate bioactivities in swiss albino mice; namely analgesic, CNS, and Oral hypoglycemic activities, while in-vitro evaluation of cytotoxicity. Methods Central nervous system activity was investigated by various method such as Elevated plus maze, Hole board, Hole cross and Open field test apparatus. Analgesic activity was evaluated by both acetic acid induced and tail immersion method. Hypoglycemic activity was evaluated by oral glucose tolerance test and cytotoxicity was evaluated by Brine shrimp lethality bioassay. Results In CNS activity, among others fractions, ASCF fraction produced a significant anxiolytic activity in both elevated plus maze and Hole board test. During open-field test almost all the fractions of A. solanacea leaves extract display decreased locomotor activities that indicates significant sedative activity. The ASME and ASCF showed significant peripheral analgesic activity at a dose of 200 mg/kg and 400 mg/kg body weight (p < 0.05). In tail immersion method, among others extracts chloroform fractions exhibited significant (p < 0.05) elongation of reaction time 30 min after oral dose of 200 and 400 mg/kg body weight respectively. The methanolic and n-hexane extracts reduced blood glucose level significantly after 90 min with value of 53.94% and 48.15% respectively (p < 0.05). In case of cytotoxicity activity, among other fractions carbon tetrachloride fraction showed lowest LC50 values. Conclusions From the above results, it is clear that different fractions of A. solanacea showed significant pharmacological potentiality in different in-vitro and in-vivo study model. So, it will be very much possible source for an isolating lead compound for curing the numerous disorders.

scholarly journals In vivo sedative and hypnotic activities of methanol extract from the leaves of Jacquemontia paniculata (Burm.f.) Hallier f. in Swiss Albino mice

2017 ◽  
Vol 28 (2) ◽  
Author(s):  
Md. Jakaria ◽  
Chayan Dhar Clinton ◽  
Mukimul Islam ◽  
Mohammad Belal Talukder ◽  
Md. Shariful Islam ◽  
...  
Keyword(s):  
Sleep Disorders ◽  
Open Field ◽  
Methanol Extract ◽  
Elevated Plus Maze ◽  
Sleeping Time ◽  
Plus Maze ◽  
Hole Board ◽  
Time Determination ◽  
Thiopental Sodium

AbstractBackground:The superior genusMethods:The sedative and hypnotic activities were evaluated by hole-cross, open field, hole-board, elevated plus maze (EPM), and thiopental sodium-induced sleeping time determination tests in mice at doses of 200 and 400 mg/kg.Results:In this investigation, we found that methanol extract ofConclusions:To conclude, these results suggest that the MEJP leaves possess potent sedative and hypnotic activities, which supported its therapeutic use for sleep disorders like insomnia.

Intranasal Paclitaxel Alters Alzheimer’s Disease Phenotypic Features in 3xTg-AD Mice

2021 ◽  
pp. 1-16
Author(s):  
Donna J. Cross ◽  
Bertrand R. Huber ◽  
Michael A. Silverman ◽  
Marcella M. Cline ◽  
Trevor B. Gill ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Axonal Transport ◽  
Elevated Plus Maze ◽  
Therapeutic Option ◽  
Cancer Therapeutics ◽  
Plus Maze ◽  
Improved Performance

Background: Microtubule stabilizing drugs, commonly used as anti-cancer therapeutics, have been proposed for treatment of Alzheimer’s disease (AD); however, many do not cross the blood-brain barrier. Objective: This research investigated if paclitaxel (PTX) delivered via the intranasal (IN) route could alter the phenotypic progression of AD in 3xTg-AD mice. Methods: We administered intranasal PTX in 3XTg-AD mice (3xTg-AD n = 15, 10 weeks and n = 10, 44 weeks, PTX: 0.6 mg/kg or 0.9%saline (SAL)) at 2-week intervals. After treatment, 3XTg-AD mice underwent manganese-enhanced magnetic resonance imaging to measure in vivo axonal transport. In a separate 3XTg-AD cohort, PTX-treated mice were tested in a radial water tread maze at 52 weeks of age after four treatments, and at 72 weeks of age, anxiety was assessed by an elevated-plus maze after 14 total treatments. Results: PTX increased axonal transport rates in treated 3XTg-AD compared to controls (p≤0.003). Further investigation using an in vitro neuron model of Aβ-induced axonal transport disruption confirmed PTX prevented axonal transport deficits. Confocal microscopy after treatment found fewer phospho-tau containing neurons (5.25±3.8 versus 8.33±2.5, p <  0.04) in the CA1, altered microglia, and reduced reactive astrocytes. PTX improved performance of 3xTg-AD on the water tread maze compared to controls and not significantly different from WT (Day 5, 143.8±43 versus 91.5±77s and Day 12, 138.3±52 versus 107.7±75s for SAL versus PTX). Elevated plus maze revealed that PTX-treated 3xTg-AD mice spent more time exploring open arms (Open arm 129.1±80 versus 20.9±31s for PTX versus SAL, p≤0.05). Conclusion: Taken collectively, these findings indicate that intranasal-administered microtubule-stabilizing drugs may offer a potential therapeutic option for treating AD.

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