scholarly journals The Antioxidative Action of ZTP by Increasing Nrf2/ARE Signal Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Liang Yang ◽  
Bing Xu ◽  
Chunxu Yuan ◽  
Zhi Dai ◽  
Yong Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Circulation ◽  
Molecular Mechanisms ◽  
Immune Reaction ◽  
Brain Diseases ◽  
Stress Injury ◽  
Cell Death Gene ◽  
Antioxidant Stress ◽  
Antioxidative Action ◽  
The Brain

So far, more than 25,000 brain diseases have been shown to be related to oxidative stress. Excessive free radicals and reactive oxygen species (ROS) can attack cells resulting in dysfunctional proteins, lipids, and nucleic acid, finally leading to imbalance of energy metabolism, cell death, gene mutation, and immune reaction. Therefore oxidative stress plays an important role in neuronal diseases. As a traditional Chinese medicine, Zhengtian Pill (ZTP) was reported to have the ability to reduce the blood viscosity of migraine model rats, with increased beta-endorphin, serotonin, adrenaline, and dopamine in brain tissue. Moreover ZTP can effectively accelerate blood circulation and attenuate blood coagulation. However, the molecular mechanisms of ZPT are still unclear. Through the behavioral test we found that ZTP can significantly improve depression-like behavior induced by LPS when rat was treated with ZTP (L 0.17 g/kg, M 0.34 g/kg, and H 0.7 g/kg) intraperitoneal injection once a day for 30 consecutive days. And ZTP can resist oxidative stress (>72 h) for a longer time. And ZTP can promote the levels of ATP and SOD and reduce the levels of ROS and MDA in the brain. At the same time, ZTP can have antioxidant stress through increasing the expression level of Nrf2/HO-1/P38. These results show that ZTP may be a potential antioxidant stress drug for variety of diseases associated with oxidative stress injury.

scholarly journals Ganglioside GM1 Targets Astrocytes to Stimulate Cerebral Energy Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Charles Finsterwald ◽  
Sara Dias ◽  
Pierre J. Magistretti ◽  
Sylvain Lengacher
Keyword(s):  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Brain Diseases ◽  
Mitochondrial Activity ◽  
Ganglioside Gm1 ◽  
Neuroprotective Effects ◽  
Wide Range ◽  
Cord Injury ◽  
Clinical Benefits ◽  
The Brain

Gangliosides are major constituents of the plasma membrane and are known to promote a number of physiological actions in the brain, including synaptic plasticity and neuroprotection. In particular, the ganglioside GM1 was found to have a wide range of preclinical and clinical benefits in brain diseases such as spinal cord injury, Huntington’s disease and Parkinson’s disease. However, little is known about the underlying cellular and molecular mechanisms of GM1 in the brain. In the present study, we show that GM1 exerts its actions through the promotion of glycolysis in astrocytes, which leads to glucose uptake and lactate release by these cells. In astrocytes, GM1 stimulates the expression of several genes involved in the regulation of glucose metabolism. GM1 also enhances neuronal mitochondrial activity and triggers the expression of neuroprotection genes when neurons are cultured in the presence of astrocytes. Finally, GM1 leads to a neuroprotective effect in astrocyte-neuron co-culture. Together, these data identify a previously unrecognized mechanism mediated by astrocytes by which GM1 exerts its metabolic and neuroprotective effects.

scholarly journals Effect of Metallothionein-III on Mercury-Induced Chemokine Gene Expression

Toxics ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 48 ◽  
Author(s):  
Jin-Yong Lee ◽  
Maki Tokumoto ◽  
Gi-Wook Hwang ◽  
Min-Seok Kim ◽  
Tsutomu Takahashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Mercury Vapor ◽  
Brain Diseases ◽  
Wild Type ◽  
Chemokine Gene ◽  
Mercury Compounds ◽  
In The Wild ◽  
The Brain ◽  
Chemokine Gene Expression

Mercury compounds are known to cause central nervous system disorders; however the detailed molecular mechanisms of their actions remain unclear. Methylmercury increases the expression of several chemokine genes, specifically in the brain, while metallothionein-III (MT-III) has a protective role against various brain diseases. In this study, we investigated the involvement of MT-III in chemokine gene expression changes in response to methylmercury and mercury vapor in the cerebrum and cerebellum of wild-type mice and MT-III null mice. No difference in mercury concentration was observed between the wild-type mice and MT-III null mice in any brain tissue examined. The expression of Ccl3 in the cerebrum and of Cxcl10 in the cerebellum was increased by methylmercury in the MT-III null but not the wild-type mice. The expression of Ccl7 in the cerebellum was increased by mercury vapor in the MT-III null mice but not the wild-type mice. However, the expression of Ccl12 and Cxcl12 was increased in the cerebrum by methylmercury only in the wild-type mice and the expression of Ccl3 in the cerebellum was increased by mercury vapor only in the wild-type mice. These results indicate that MT-III does not affect mercury accumulation in the brain, but that it affects the expression of some chemokine genes in response to mercury compounds.

scholarly journals Methamphetamine-Triggered Neurotoxicity in Human Dorsolateral Prefrontal Cortex

2021 ◽  
Vol 10 ◽  
pp. 2016
Author(s):  
Ali Zare ◽  
Alireza Ghanbari ◽  
Mohammad Javad Hoseinpour ◽  
Mahdi Eskandarian Boroujeni ◽  
Alimohammad Alimohammadi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Metabolic Activation ◽  
Neural Cells ◽  
Dorsolateral Prefrontal ◽  
The Central Nervous System ◽  
The Brain

Background: Methamphetamine (MA), is an extremely addictive stimulant that adversely affects the central nervous system. Accumulating evidence indicates that molecular mechanisms such as oxidative stress, apoptosis, and autophagy are involved in the toxicity of MA. Considering experimental animal studies exhibiting MA-induced neurotoxicity, the relevance of these findings needs to be evidently elucidated in human MA users. It is generally assumed that multiple chemical substances released in the brain following MA-induced metabolic activation are primary factors underlying damage of neural cells. Hence, this study aimed to investigate the role of autophagy and apoptosis as well as oxidative stress in the brain of postmortem MA-induced toxicity. Materials and Methods: In this study, we determine the gene expression of autophagy and apoptosis, including BECN1, MAP1ALC3, CASP8, TP53, and BAX genes in ten healthy controls and ten chronic users of MA postmortem dorsolateral prefrontal cortex (DLPFC) by real-time polymerase chain reaction. Also, we applied immunohistochemistry in formalin-fixed and paraffin-embedded human brain samples to analyze brain-derived neurotrophic factor (BDNF). Also, spectrophotometry was performed to measure glutathione (GSH) content. Results: The expression level of apoptotic and autophagic genes (BECN1, MAP1ALC3, CASP8, TP53, and BAX) were significantly elevated, while GSH content and BDNF showed substantial reductions in DLPFC of chronic MA users. Discussion: Our data showed that MA addiction provokes transduction pathways, namely apoptosis and autophagy, along with oxidative mechanisms in DLPFC. Also, MA induces multiple functional and structural perturbations in the brain, determining its toxicity and possibly contributing to neurotoxicity. [GMJ.2021;10:e2016]

scholarly journals Diabetes and Alzheimer’s Disease: Might Mitochondrial Dysfunction Help Deciphering the Common Path?

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1257
Author(s):  
Maria Assunta Potenza ◽  
Luca Sgarra ◽  
Vanessa Desantis ◽  
Carmela Nacci ◽  
Monica Montagnani
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Senile Plaques ◽  
Mitochondrial Activity ◽  
Enhanced Production ◽  
The Common ◽  
The Brain

A growing number of clinical and epidemiological studies support the hypothesis of a tight correlation between type 2 diabetes mellitus (T2DM) and the development risk of Alzheimer’s disease (AD). Indeed, the proposed definition of Alzheimer’s disease as type 3 diabetes (T3D) underlines the key role played by deranged insulin signaling to accumulation of aggregated amyloid beta (Aβ) peptides in the senile plaques of the brain. Metabolic disturbances such as hyperglycemia, peripheral hyperinsulinemia, dysregulated lipid metabolism, and chronic inflammation associated with T2DM are responsible for an inefficient transport of insulin to the brain, producing a neuronal insulin resistance that triggers an enhanced production and deposition of Aβ and concomitantly contributes to impairment in the micro-tubule-associated protein Tau, leading to neural degeneration and cognitive decline. Furthermore, the reduced antioxidant capacity observed in T2DM patients, together with the impairment of cerebral glucose metabolism and the decreased performance of mitochondrial activity, suggests the existence of a relationship between oxidative damage, mitochondrial impairment, and cognitive dysfunction that could further reinforce the common pathophysiology of T2DM and AD. In this review, we discuss the molecular mechanisms by which insulin-signaling dysregulation in T2DM can contribute to the pathogenesis and progression of AD, deepening the analysis of complex mechanisms involved in reactive oxygen species (ROS) production under oxidative stress and their possible influence in AD and T2DM. In addition, the role of current therapies as tools for prevention or treatment of damage induced by oxidative stress in T2DM and AD will be debated.

scholarly journals Elucidating the Multi-Targeted Role of Nutraceuticals: A Complementary Therapy to Starve Neurodegenerative Diseases

2021 ◽  
Vol 22 (8) ◽  
pp. 4045
Author(s):  
Tapan Behl ◽  
Gagandeep Kaur ◽  
Aayush Sehgal ◽  
Sukhbir Singh ◽  
Saurabh Bhatia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Financial Burden ◽  
Complementary Therapy ◽  
Therapeutic Interventions ◽  
Multifactorial Diseases ◽  
Mitochondrial Homeostasis ◽  
Attractive Option ◽  
The Brain

The mechanisms underlying multifactorial diseases are always complex and challenging. Neurodegenerative disorders (NDs) are common around the globe, posing a critical healthcare issue and financial burden to the country. However, integrative evidence implies some common shared mechanisms and pathways in NDs, which include mitochondrial dysfunction, neuroinflammation, oxidative stress, intracellular calcium overload, protein aggregates, oxidative stress (OS), and neuronal destruction in specific regions of the brain, owing to multifaceted pathologies. The co-existence of these multiple pathways often limits the advantages of available therapies. The nutraceutical-based approach has opened the doors to target these common multifaceted pathways in a slow and more physiological manner to starve the NDs. Peer-reviewed articles were searched via MEDLINE and PubMed published to date for in-depth research and database collection. Considered to be complementary therapy with current clinical management and common drug therapy, the intake of nutraceuticals is considered safe to target multiple mechanisms of action in NDs. The current review summarizes the popular nutraceuticals showing different effects (anti-inflammatory, antioxidant, neuro-protectant, mitochondrial homeostasis, neurogenesis promotion, and autophagy regulation) on vital molecular mechanisms involved in NDs, which can be considered as complementary therapy to first-line treatment. Moreover, owing to its natural source, lower toxicity, therapeutic interventions, biocompatibility, potential nutritional effects, and presence of various anti-oxidative and neuroprotective constituents, the nutraceuticals serve as an attractive option to tackle NDs.

scholarly journals Multifunctional Polymeric Nanoplatforms for Brain Diseases Diagnosis, Therapy and Theranostics

Biomedicines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 13 ◽  
Author(s):  
Shahryar Shakeri ◽  
Milad Ashrafizadeh ◽  
Ali Zarrabi ◽  
Rasoul Roghanian ◽  
Elham Ghasemipour Afshar ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Human Serum Albumin ◽  
Blood Circulation ◽  
Delivery Systems ◽  
Brain Diseases ◽  
Drug Penetration ◽  
The Central Nervous System ◽  
Diagnosis Therapy ◽  
The Brain

The blood–brain barrier (BBB) acts as a barrier to prevent the central nervous system (CNS) from damage by substances that originate from the blood circulation. The BBB limits drug penetration into the brain and is one of the major clinical obstacles to the treatment of CNS diseases. Nanotechnology-based delivery systems have been tested for overcoming this barrier and releasing related drugs into the brain matrix. In this review, nanoparticles (NPs) from simple to developed delivery systems are discussed for the delivery of a drug to the brain. This review particularly focuses on polymeric nanomaterials that have been used for CNS treatment. Polymeric NPs such as polylactide (PLA), poly (D, L-lactide-co-glycolide) (PLGA), poly (ε-caprolactone) (PCL), poly (alkyl cyanoacrylate) (PACA), human serum albumin (HSA), gelatin, and chitosan are discussed in detail.

Sulforaphane Reverses the Amyloid-β Oligomers Induced Depressive-Like Behavior

2020 ◽  
Vol 78 (1) ◽  
pp. 127-137 ◽  
Author(s):  
Wei Wang ◽  
Cuibai Wei ◽  
Meina Quan ◽  
Tingting Li ◽  
Jianping Jia
Keyword(s):  
Oxidative Stress ◽  
Memory Impairment ◽  
Molecular Mechanisms ◽  
Psychological Symptoms ◽  
Amyloid Β ◽  
Serotonergic System ◽  
Inflammatory Factors ◽  
The Relationship ◽  
The Brain ◽  
And Oxidative Stress

Background: Depression is one of the most common behavioral and psychological symptoms in people with Alzheimer’s disease (AD). To date, however, the molecular mechanisms underlying the clinical association between depression and AD remained elusive. Objective: Here, we study the relationship between memory impairment and depressive-like behavior in AD animal model, and investigate the potential mechanisms. Methods: Male SD rats were administered amyloid-β oligomers (AβOs) by intracerebroventricular injection, and then the depressive-like behavior, neuroinflammation, oxidative stress, and the serotonergic system were measured in the brain. Sulforaphane (SF), a compound with dual capacities of anti-inflammation and anti-oxidative stress, was injected intraperitoneally to evaluate the therapeutic effect. Results: The results showed that AβOs induced both memory impairment and depressive-like behavior in rats, through the mechanisms of inducing neuroinflammation and oxidative stress, and impairing the serotonergic axis. SF could reduce both inflammatory factors and oxidative stress parameters to protect the serotonergic system and alleviate memory impairment and depressive-like behavior in rats. Conclusion: These results provided insights into the biological mechanisms underlying the clinical link between depressive disorder and AD, and offered new drug options for the treatment of depressive symptoms in dementia.

scholarly journals Triggers and Effectors of Oxidative Stress at Blood-Brain Barrier Level: Relevance for Brain Ageing and Neurodegeneration

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Ana-Maria Enciu ◽  
Mihaela Gherghiceanu ◽  
Bogdan O. Popescu
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
Wide Spectrum ◽  
Cell Signalling ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Blood Brain ◽  
Brain Ageing

As fundamental research advances, it is becoming increasingly clear that a clinically expressed disease implies a mixture of intertwining molecular disturbances. Oxidative stress is one of such pathogenic pathways involved in virtually all central nervous system pathologies, infectious, inflammatory, or degenerative in nature. Since brain homeostasis largely depends on integrity of blood-brain barrier (BBB), many studies focused lately on BBB alteration in a wide spectrum of brain diseases. The proper two-way molecular transfer through BBB depends on several factors, including the functional status of its tight junction (TJ) complexes of proteins sealing neighbour endothelial cells. Although there is abundant experimental work showing that oxidative stress associates BBB permeability alteration, less is known about its implications, at molecular level, in TJ protein expression or TJ-related cell signalling. In this paper, oxidative stress is presented as a common pathway for different brain pathogenic mechanisms which lead to BBB dysregulation. We revise here oxidative-induced molecular mechanisms of BBB disruption and TJ protein expression alteration, in relation to ageing and neurodegeneration.

scholarly journals Influence of cadmium contamination on brain glial cells: consequences and bioindication possibilities

2020 ◽  
Vol 49 ◽  
pp. 67-83
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
A. M. Hahut ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Glial Cells ◽  
Functional Activity ◽  
Molecular Mechanisms ◽  
Glucose Utilization ◽  
Animal Health ◽  
Toxic Effects ◽  
Low Doses ◽  
Cellular Models ◽  
The Brain

Cadmium (Cd) is a heavy metal that currently presents in almost all components of the environment. Cd is a ubiquitous pollutant that is constantly entering the environment from industry and agriculture, mining, forest fires and many more sources. Some occupational diseases have aftereffects associated with Cd cytotoxicity. Despite long-term studies of the toxic effects of Cd, its cytotoxicity of low doses and the chronic effects on the nerve tissue cells remain undiscovered. The results of determining the Cd neurotoxicity indicate a disturbance of the permeability of the blood-brain barrier, the accumulation of Cd in the brain and the deterioration of the functional activity of the central nervous system. One of the main cellular targets for Cd in the brain are astrocytes. Astrocytes provide nutrition and functional activity of neurons, as well as recovery of physical and metabolic damage. The cytoskeleton of astrocytes is built of glial fibrillary acidic protein (GFAP). GFAP participates in important functions of astrocytes and its condition reflects the astrocytes reactivity. The molecular mechanisms of the neurotoxic effects of Cd on the glial cytoskeleton remain unknown. Glioblastomas are widely used to study the cytotoxic mechanisms of various compounds, including heavy metals, as cellular models of astrocytes. Taking into account the role of oxidative stress in a cell damage, as well as the reactive response of glial cells, we study the influence of low doses of Cd on oxidative stress and expression of GFAP and glucose-6-phosphate dehydrogenase (G6PD) in U373GM cells. Doses of 2-10 μM Cd induced a dose-dependent increase in reactive oxygen species and lipid peroxidation products. The same doses inhibited the expression of the cytoskeletal marker of astrocytes (GFAP) and metabolic marker of glucose utilization (G6PD). The obtained results indicate a pronounced cytotoxic effect of low doses of Cd in the astrocytic cell model U373GM. In addition, the astroglial cytotoxicity of Cd may be mediated by oxidative damage, inhibition of glial intermediate filament expression, and glucose utilization disorders. These parameters can be promising biomarkers of toxic effects both for the assessment of human and animal health and for determining the state of the environment as a whole.

Rare Ginsenoside 20(R)-Rg3 Inhibits D-Galactose-Induced Liver and Kidney Injury by Regulating Oxidative Stress-Induced Apoptosis

2020 ◽  
Vol 48 (05) ◽  
pp. 1141-1157 ◽  
Author(s):  
Wei Li ◽  
Jian-Qiang Wang ◽  
Yan-Dan Zhou ◽  
Jin-Gang Hou ◽  
Ying Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Treated Group ◽  
High Dose ◽  
Lipid Peroxidation Product ◽  
Stress Injury ◽  
Beneficial Effects ◽  
Liver And Kidney ◽  
Induced Apoptosis

Oxidative stress is considered as a major factor in aging and exacerbates aging process through a variety of molecular mechanisms. D-galactose, a normal reducing sugar with high dose can cause the accumulation of reactive oxygen species (ROS) or stimulate free radical production indirectly by the formation of advanced glycation end products in tissues, finally resulting in oxidative stress. 20(R)-ginsenoside Rg3 (20(R)-Rg3), a major and representative component isolated from red ginseng (Panax ginseng C.A Meyer), has been shown to observably have an anti-oxidative effect. We thereby investigated the beneficial effects of 20(R)-Rg3 on D-galactose-induced oxidative stress injury and its underlying mechanisms. Our results showed that continuous injection of D-galactose with 800[Formula: see text]mg/kg/day for 8 weeks increased the levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). However, such increases were attenuated by the treatment of 20(R)-Rg3 for 4 weeks. Meanwhile, 20(R)-Rg3 markedly inhibited D-galactose-caused oxidative stress in liver and kidney. The anti-oxidants, including catalase (CAT) and superoxide dismutase (SOD), were elevated in the mice from 20(R)-Rg3-treated group compared with that from D-galactose group. In contrast, a significant decrease in levels of cytochrome P450 E1 (CYP2E1) and the lipid peroxidation product malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were observed in the 20(R)-Rg3-treated group. These effects were associated with a significant increase of AGEs. More importantly, 20(R)-Rg3 effectively attenuated D-galactose induced apoptosis in liver and kidney via restoring the upstream PI3K/AKT signaling pathway. Taken together, our study suggests that 20(R)-Rg3 may be a novel and promising anti-oxidative therapeutic agent to prevent aging-related injuries in liver and kidney.

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