Administration of Quercetin Ameliorates Lipopolysaccharide Induced Neuroinflammation and Oxidative Stress in Adult Zebrafish

Abstract Background: Quercetin is a natural flavonoid which is known to have numerous pharmacological activities such as antioxidative, anti-inflammatory and neuroprotective effects against various neurological disorders. Lipopolysaccharide (LPS) is a potent endotoxin, reported to cause various neurological disorders such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Stroke (Brain Attack), Meningitis. Aim: The present study was designed to investigate the possibility thatquercetin ameliorates LPS induced oxidative stress and neuroinflammation in adult zebrafish. Materials and methods: Zebrafish (weighing 470-530 mg) were treated with single injection of LPS (1 mg/kg) intraperitoneally (i.p.) followed by post treatment for 7 days with quercetin (50 and 100 mg/kg; i.p.). After sacrificed, brain was harvested and subjected for biochemical, molecular and histological analyses. Results: Results revealed post treatment with quercetin was able to ameliorate the behavioral abnormalities as in novel diving test- time spent in top zone (TSTZ), and number of entries in top zone was significantly more as compared to time spent in bottom zone (TSBZ). In light-dark chamber test- time spent in light zone (TSLZ), and number of entries in light zone was significantly more as compared to time spent in dark compartment (TSDC). Additionally, results of histopathology (H & E stain) studies showed less disruption in neuronal cells as compared to LPS treated group. Moreover, results of molecular analysis implies that quercetin treatment significantly decrease TNF-α and IL-1β level as compared to LPS treated animals. Further, results of biochemical analysis reveal that quercetin reduce the level of LPO, nitrite, AChEs and increases anti-oxidant GSH. Conclusion: Quercetin treatment helps to prevent oxidative damage and neuroinflammation in LPS treated adult zebrafish.

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Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model

International Journal of Molecular Sciences ◽

10.3390/ijms22031285 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1285

Author(s):

Seong Soon Kim ◽

Hyemin Kan ◽

Kyu-Seok Hwang ◽

Jung Yoon Yang ◽

Yuji Son ◽

...

Keyword(s):

Oxidative Stress ◽

Epileptic Seizure ◽

Neurological Disorders ◽

Aminobutyric Acid ◽

Oxygen Species ◽

Gamma Aminobutyric Acid ◽

Zebrafish Model ◽

Neuroprotective Effects ◽

Drug Discovery And Development ◽

Spontaneous Seizures

Epilepsy is one of the most common neurological disorders, and it is characterized by spontaneous seizures. In a previous study, we identified 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as a novel anti-epileptic agent in chemically- or genetically-induced epileptic zebrafish and mouse models. In this study, we investigated the anti-epileptic effects of GM-90432 through neurochemical profiling-based approach to understand the neuroprotective mechanism in a pentylenetetrazole (PTZ)-induced epileptic seizure zebrafish model. GM-90432 effectively improved PTZ-induced epileptic behaviors via upregulation of 5-hydroxytryptamine, 17-β-estradiol, dihydrotestosterone, progesterone, 5α -dihydroprogesterone, and allopregnanolone levels, and downregulation of normetanephrine, gamma-aminobutyric acid, and cortisol levels in brain tissue. GM-90432 also had a protective effect against PTZ-induced oxidative stress and zebrafish death, suggesting that it exhibits biphasic neuroprotective effects via scavenging of reactive oxygen species and anti-epileptic activities in a zebrafish model. In conclusion, our results suggest that neurochemical profiling study could be used to better understand of anti-epileptic mechanism of GM-90432, potentially leading to new drug discovery and development of anti-seizure agents.

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Pharmacotherapeutic Potential of Garlic in Age-Related Neurological Disorders

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527320666210927101257 ◽

2021 ◽

Vol 20 ◽

Author(s):

Ramin Ahangar-Sirous ◽

Mohadeseh Poudineh ◽

Arina Ansari ◽

Ali Nili ◽

Seyyed Mohammad Matin Alavi Dana ◽

...

Keyword(s):

Public Health ◽

Oxidative Stress ◽

Neurological Disorders ◽

Allium Sativum ◽

Aged Garlic Extract ◽

Neuroprotective Effects ◽

Age Related ◽

Pathologic Features ◽

The Common ◽

Aged Garlic

: Age-related neurological disorders [ANDs] involve neurodegenerative diseases [NDDs] such as Alzheimer's disease [AD], the most frequent kind of dementia in elderly people, and Parkinson's disease [PD], and also other disorders like epilepsy and migraine. Although ANDs are multifactorial, Aging is a principal risk factor for them. The common and most main pathologic features among ANDs are inflammation, oxidative stress, and misfolded proteins accumulation. Since failing brains caused by ANDs impose a notable burden on public health and their incidence is increasing, a lot of works has been done to overcome them. Garlic, Allium sativum, has been used for different medical purposes globally and more than thousands of publications have reported its health benefits. Garlic and aged garlic extract are considered potent anti-inflammatory and antioxidants agents and can have remarkable neuroprotective effects. This review is aimed to summarize knowledge on the pharmacotherapeutic potential of garlic and its components in ANDs.

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The Neuroprotective Effects of Astaxanthin: Therapeutic Targets and Clinical Perspective

Molecules ◽

10.3390/molecules24142640 ◽

2019 ◽

Vol 24 (14) ◽

pp. 2640 ◽

Cited By ~ 20

Author(s):

Fakhri ◽

Aneva ◽

Farzaei ◽

Sobarzo-Sánchez

Keyword(s):

Oxidative Stress ◽

Neurodegenerative Disorders ◽

Neurological Disorders ◽

Spinal Cord Injuries ◽

Neurological Diseases ◽

Mechanisms Of Action ◽

Clinical Perspective ◽

Neuroprotective Effects ◽

Brain And Spinal Cord ◽

Neuronal Disorders

As the leading causes of human disability and mortality, neurological diseases affect millions of people worldwide and are on the rise. Although the general roles of several signaling pathways in the pathogenesis of neurodegenerative disorders have so far been identified, the exact pathophysiology of neuronal disorders and their effective treatments have not yet been precisely elucidated. This requires multi-target treatments, which should simultaneously attenuate neuronal inflammation, oxidative stress, and apoptosis. In this regard, astaxanthin (AST) has gained growing interest as a multi-target pharmacological agent against neurological disorders including Parkinson’s disease (PD), Alzheimer’s disease (AD), brain and spinal cord injuries, neuropathic pain (NP), aging, depression, and autism. The present review highlights the neuroprotective effects of AST mainly based on its anti-inflammatory, antioxidative, and anti-apoptotic properties that underlies its pharmacological mechanisms of action to tackle neurodegeneration. The need to develop novel AST delivery systems, including nanoformulations, targeted therapy, and beyond, is also considered.

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Neuroprotective Effects of Low Dose Anandamide in Pentylenetetrazole-Induced Kindling in Rats

Biomedical & Pharmacology Journal ◽

10.13005/bpj/1610 ◽

2019 ◽

Vol 12 (1) ◽

pp. 25-40 ◽

Cited By ~ 3

Author(s):

Omar M. E. Abdel-Salam ◽

Amany A. Sleem ◽

Marawan Abd El-Baset Mohamed Sayed ◽

Eman R. Youness ◽

Nermeen Shaffie

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Neutrophil Elastase ◽

Cannabinoid Receptor ◽

Treated Group ◽

Paraoxonase 1 ◽

Neuroprotective Effects ◽

Chemical Kindling ◽

Brain Oxidative Stress ◽

Endogenous Cannabinoid

Anandamide (N-arachidonoylethanolamine) is an endogenous cannabinoid receptor CB1 ligand that exhibits neuroprotective effects in the brain. In this study, the effect of exogenously given anandamide on pentylenetetrazole (PTZ)-induced chemical kindling oxidative stress and brain damage in rats was studied. Rats were intraperitoneally (i.p.) injected with 35 mg/kg PTZ once every 48 hours for 12 times to induce seizures. Anandamide was i.p. given. 30 min prior to PTZ injection at 100 or 200 mg/kg. Injections of PTZ induced significant increase in brain lipid peroxidation (malondialdehyde: MDA), and nitric oxide associated with marked decrease in brain reduced glutathione (GSH). There were also significant decrements in acetylcholinesterase (AChE) concentration, butyrylcholinesterase (BChE) and paraoxonase-1 (PON-1) activities in brain tissue of PTZ injected rats. Meanwhile, there was no significant effect for PTZ on the concentration of brain neutrophil elastase. Anandamide administered at 100 and 200 mg/kg significantly decreased MDA and increased GSH contents and at 200 mg/kg significantly decreased nitric oxide in brain of PTZ-treated rats. The drug also caused significant increments in AChE concentration and PON-1 activity but had no significant effect on BChE or neutrophil elastase in rats treated with PTZ. Anandamide given at the dose of 200mg/kg significantly decreased the mean seizure scores over the study period by 22.3% and the frequency of myoclonic jerks and rearing (stage 3) by 56.7% compared with the vehicle-treated group. Anandamide given at 100 and 200 mg/kg completely inhibited the development of generalized tonic-clonic seizures (stage 5). It is concluded that in the PTZ-induced seizures, the cannabinoid receptor CB1 agonist anandamide decreases brain oxidative stress, neuronal injury, and exerts an antiepileptic activity.

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Virgin Coconut Oil Ameliorates Colchicine Induced Cognitive Dysfunction- A Preclinical Study

Pharmaceutical Sciences ◽

10.34172/ps.2019.61 ◽

2020 ◽

Vol 26 (1) ◽

pp. 1-12

Author(s):

Jeena John ◽

Naveen Kumar Sapa ◽

Rekha R Shenoy

Keyword(s):

Oxidative Stress ◽

Fatty Acids ◽

Frontal Cortex ◽

Cognitive Dysfunction ◽

Unsaturated Fatty Acids ◽

Ketone Bodies ◽

Coconut Oil ◽

Treated Group ◽

Virgin Coconut Oil ◽

Neuroprotective Effects

Background : Virgin coconut oil (VCO) has been identified as a potential cognitive strengthener associated with Alzheimer’s disease (AD). It contains medium chain fatty acids (MCFA) which are absorbed and easily metabolized by the liver to form ketone bodies. Ketone bodies are converted to acetyl Co-A in the brain which then enters the citric acid cycle to provide ATP and also serves as precursors of acetylcholine in neurons. Sunflower oil (SO) contains poly unsaturated fatty acids which has both anti-inflammatory and neuroprotective actions. To compare the neuroprotective effects of VCO and SO on biochemical parameters involved in the cognitive dysfunction induced by colchicine through intracerebroventricular (i.c.v) route.To assess the role of polyphenols and MCFA present in VCO in preventing oxidative stress and its influence on in neuroprotection and memory enhancement. Methods: In the present study, we induced dementia through i.c.v injection of colchicine after giving the diet enriched VCO and SO in rats for 60 days. Rats were sacrificed on the 22nd day after the administration of colchicine. Behavioral parameters were assessed during the study period and biochemical estimations were performed using frontal cortex and hippocampus isolated from rat brain. Results: From the memory and learning tests by Morris water maze, VCO treated group performed better than SO treated rats. VCO reversed the antagonistic effects induced by colchicine by decreasing the acetylcholinesterase and malondialdehyde levels and increasing the levels of catalase and superoxide dismutase. SO only reduced malondialdehyde levels in cortex and hippocampus. Conclusion: The results demonstrated potential beneficiary effects of VCO in the cognitive dysfunction induced by colchicine by enhancing acetylcholine levels in the frontal cortex and hippocampus and also by reducing oxidative stress induced by physiological oxidants.

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Neuroprotective effects of taurine on SH-SY5Y cells under hydrocortisone induced stress

Research Society and Development ◽

10.33448/rsd-v10i9.18426 ◽

2021 ◽

Vol 10 (9) ◽

pp. e55510918426

Author(s):

Rafaella Carvalho Rossato ◽

Alessandro Eustaquio Campos Granato ◽

Carlos Dailton Guedes de Oliveira Moraes ◽

Geisa Nogueira Salles ◽

Cristina Pacheco Soares

Keyword(s):

Oxidative Stress ◽

Neurodegenerative Disorder ◽

Memory Loss ◽

Study Strategies ◽

Neuroprotective Effects ◽

Human Neuroblastoma ◽

Induced Stress ◽

Behavioral Abnormalities ◽

First Time

Alzheimer's disease (AD) is the most common, progressive and irreversible neurodegenerative disorder, characterized by memory loss, cognitive impairment and behavioral abnormalities. Although there is no cure, several study strategies seek to elucidate mechanisms of the disease. Recent studies address the benefits of taurine. Thus, the present study aims to analyze neuroprotective effects of taurine in human neuroblastoma (SH-SY5Y), using an in vitro experimental model of oxidative stress induced by hydrocortisone. This work showed for the first time that taurine can promote neuroprotection in SH-SY5Y under oxidative stress caused by hydrocortisone. Cell viability was evaluated using crystal violet and the evaluation of cell morphology was performed by scanning electron microscopy (SEM). The viability of SH-SY5Y pre-treated with taurine and stressed with hydrocortisone was preserved, compared to the stressed only group, which was also morphologically observed. Therefore, taurine can represent a considerable therapeutic candidate in the prevention of neurodegenerative diseases, such as AD.

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Ingredients for Functional Drinks in Neurodegenerative Diseases: A Review

Natural Product Communications ◽

10.1177/1934578x0900400508 ◽

2009 ◽

Vol 4 (5) ◽

pp. 1934578X0900400

Author(s):

Pilar Zafrilla ◽

Juana M Morulas ◽

José M. Rubio-Perez ◽

Emma Cantos Villar

Keyword(s):

Oxidative Stress ◽

Neurodegenerative Diseases ◽

Neurological Disorders ◽

Clinical Evidence ◽

The Body ◽

Neuroprotective Effects ◽

Antioxidant Agents ◽

Rate Of Progression ◽

The Brain

Several studies have indicated that oxidative stress is a major risk factor for the initiation and progression of neurological disorders like Parkinson's disease (PD) and Alzheimer's (AD). Therefore, reducing oxidative stress appears to be a rational choice for the prevention and reduction in the rate of progression of these neurological disorders. The brain utilizes about 25% of respired oxygen even though it represents only 5% of the body weight. Free radicals are generated during the normal intake of oxygen, during infection, and during normal oxidative metabolism of certain substrates. Although experimental data are consistent in demonstrating the neuroprotective effects of antioxidants in vitro and in animal models, the clinical evidence that antioxidant agents may prevent or slow the course of these diseases is still relatively unsatisfactory, and insufficient to strongly modify clinical practice. In this paper, natural possible substances that could be added to a beverage to prevent or decrease the developing of neurodegenerative diseases are reviewed.

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Pre-Treatment with Quercetin Prevents Dementia in Streptozotocin Treated Zebrafish via Modulation of Neuroinflammation and Oxidative Stress

10.21203/rs.3.rs-721175/v1 ◽

2021 ◽

Author(s):

Nilima Pradhan ◽

Bhawna Devi ◽

Deepali Sharma ◽

Charan Singh ◽

Arti Singh

Keyword(s):

Oxidative Stress ◽

Open Field ◽

Field Test ◽

Open Field Test ◽

Treated Group ◽

Normal Group ◽

Histopathological Analysis ◽

Adult Zebrafish ◽

Maze Test ◽

Pre Treatment

Abstract Aim: To examine the protective outcome of quercetin against streptozotocin induced dementia in adult zebrafish. Materials and method: In this study, adult zebrafish (weighing 470-530 mg) were subjected to the streptozotocin administration (300 mg/kg; i.p) followed by a quercetin (50 & 100mg/kg i.p) pre-treatment before 24 hr of streptozotocin administration followed by blood glucose level measurement, behavioral parameters (light-dark test, novel diving test, open field test and T-maze test), biochemical parameters (lipid peroxidase, reduced glutathione, nitrite and AChEs activity), molecular and histopathological analysis. Results: In light-dark test, streptozotocin treated zebrafish shown their preference in dark compartment as compared to normal group. In novel diving tank, streptozotocin zebrafish spent less time and decrease in total number of entries to the top zone when compared to the normal group. In the T-maze test, streptozotocin treated zebrafish has shown significantly more time spent in unfavorable zone and less time spent in favorable zone with increase in total latency as compared to normal group. However, in the open field test no significant effect was seen among any group. Moreover, pre-treatment with quercetin (50 mg/kg and 100 mg/kg) significantly ameliorated the memory deficits in all the behavioral, biochemical and molecular parameters as compared to animals treated with streptozotocin. Additionally, results of histopathology studies showed less disruption in neuronal cells in quercetin treated group when compared to STZ treated animals.Conclusion: Pre-treatment with quercetin ameliorates streptozotocin induced dementia in adult zebrafish by preventing oxidative stress and neuroinflammation.

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Neuroprotective effects of taurine and 3-hydroxypyridine derivatives in the intracerebral hemorrhage model in rats

Research Results in Pharmacology ◽

10.3897/rrpharmacology.5.36988 ◽

2019 ◽

Vol 5 (3) ◽

pp. 87-94

Author(s):

Natalia I. Nesterova ◽

Olesya V. Shcheblykina ◽

Pavel D. Kolesnichenko ◽

Arkady V. Nesterov ◽

Dmitry V. Shcheblykin ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Neurological Disorders ◽

Neuroprotective Effect ◽

Treated Group ◽

Control Group ◽

Stroke Index ◽

Neuroprotective Effects ◽

Rapid Reduction ◽

Lower Severity ◽

Derivatives Of

Introduction: At present, the problem of pharmacological correction of free radical processess emerges full-blown. The aim of the study is an experimental study of the neuroprotective effect of taurine and 3-hydroxypyridine derivatives. Materials and methods: The study was performed in Wistar rats. The neuroprotective effect of the substances was studied in the intracerebral hemorrhage model. Results and discussion: The administration of the studied substances had a positive effect on the survival of the animals within the first day (50% of rats died in the control group, 30% – in the Mexidol- and Ethoxidol-treated groups, and 20% – in LKhT 3-17-treated group). Within the first day after the surgery, all rats with stroke had severe neurological disorders. However, by the 3rd day, the Ethoxidol- and LKhT 3-17-treated rats had a lower neurological deficit. By Day 14, all groups of animals treated with the test substances had a lower severity of post-stroke disorders than those in the control group, which was evident as a 1.5-time lower McGraw Stroke Index score. LKhT 3-17 substance showed the most pronounced neuroprotective effect. Conclusions: The studied derivatives of taurine and 3-hydroxypyridine have a neuroprotective effect, which is manifested in the lower severity of neurological disorders,a more rapid reduction in the signs of neurodegeneration and accelerated hemorrhage processes.

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Ultrastructure of bronchopulmonary lavage cells from bovines administered 3-methylindole: II. 24 hours post-treatment

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100111124 ◽

1984 ◽

Vol 42 ◽

pp. 202-203

Author(s):

Amreek Singh ◽

Judith M. McLaren ◽

Onkar S. Atwal ◽

Peter Eyre

Keyword(s):

Plasma Cells ◽

Ciliated Cell ◽

Lavage Fluid ◽

Treated Group ◽

Post Treatment ◽

Lung Edema ◽

Ciliated Cells ◽

Thin Sections ◽

Variable Diameter ◽

Cell Pellet

Introduction3-methylindole (MI), a rumen metabolite of the amino acid L-tryptophan, has been shown to produce bovine pulmonary edema and emphysema. The airways contain free and exfoliated cells. A morphologic analysis of these cells may complement the understanding of the mechanism of lung edema. Ultrastructure of the bronchopulmonary lavage (BL) cells 24 h following MI oral administration to calves is described in this experiment. The 12 hours post-treatment results were described earlier.Materials and MethodsTwo Holstein-Friesian calves were each administered an oral dose of 0.2 g MI/Kg body weight and another two calves served as controls. The animals were euthanized with sodium pentabarbitol 24 h after receiving the compound. The lungs and trachea were removed and 0.1 M sodium phosphate buffered saline was infused into the lungs through the trachea. Glutaraldehyde fixative was added to the recovered BL fluid so as to form a 1% solution. The fluid was centrifuged and the resulting cell pellet was suspended in the buffer. The procedures were repeated on the suspension; the pellet was post-fixed in osmium tetroxide and was processed by conventional methods of section preparations for TEM examination. Lung samples from caudal lobes were fixed in 1.5% glutaraldehyde to obtain tissue sections for TEM.Results and DiscussionPulmonary alveolar macrophages (AM), neutrophils, ciliated epithelial cells, globule leukocytes and plasma cells were recovered from the BL fluid of the control and Mi-administered calves. Ciliated cells and globule leukocytes could not be harvested from the controls. The AM obtained from the treated calves (Fig. 1) in comparison with similar cells from the controls were larger, and contained large membrane-limited inclusions (phagolysosomes). There was a remarkable similarity between the lavaged AM and the AM studied in thin sections of lung (cf. Fig. 1 and Fig. 2). The neutrophil was the second most abundant cell type retrieved from the lavage fluid from the calves of control or treated group. Except for scanty pseudopodia in the neutrophils obtained from the Mi-receiving calves, the cells appeared unaltered (Fig. 3). Ciliated cells were abundant in the BL fluid of Mi-ingesting calves. A heterogeneous collection of vesicles filled the ciliated cell cytoplasm (Fig. 3). Globule leukocytes were commonly observed among BL cells of treated calves. The globule leukocytes were ca. 15 μm in diameter and contained round or elliptical nuclei with conspicuous nucleoli. The cytoplasmic granules, which are a prominent feature of globule leukocytes, were electron-opaque and had a variable diameter (0.5-3.0 μm). A one-line account of globule leukocytes in the bronchi of steers administered MI has appeared. Plasma cells were rare. Ultrastructure of BL cells is compatible with their response to chemical insult by MI.

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