A Mechanistic Evaluation of Antioxidant Nutraceuticals on Their Potential against Age-Associated Neurodegenerative Diseases

Nutraceuticals have been extensively studied worldwide due to its neuroprotective effects in in vivo and in vitro studies, attributed by the antioxidative properties. Alzheimer (AD) and Parkinson disease (PD) are the two main neurodegenerative disorders that are discussed in this review. Both AD and PD share the similar involvement of oxidative stress in their pathophysiology. Nutraceuticals exert their antioxidative effects via direct scavenging of free radicals, prevent damage to biomolecules, indirectly stimulate the endogenous antioxidative enzymes and gene expressions, inhibit activation of pro-oxidant enzymes, and chelate metals. In addition, nutraceuticals can act as modulators of pro-survival, pro-apoptotic, and inflammatory signaling pathways. They have been shown to be effective particularly in preclinical stages, due to their multiple mechanisms of action in attenuating oxidative stress underlying AD and PD. Natural antioxidants from food sources and natural products such as resveratrol, curcumin, green tea polyphenols, and vitamin E are promising therapeutic agents in oxidative stress-mediated neurodegenerative disease as they have fewer adverse effects, more tolerable, cheaper, and sustainable for long term consumption.

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Resveratrol Delivery from Implanted Cyclodextrin Polymers Provides Sustained Antioxidant Effect on Implanted Neural Probes

International Journal of Molecular Sciences ◽

10.3390/ijms21103579 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3579 ◽

Cited By ~ 2

Author(s):

Rebecca M. Haley ◽

Sean T. Zuckerman ◽

Hassan Dakhlallah ◽

Jeffery R. Capadona ◽

Horst A. von Recum ◽

...

Keyword(s):

Oxidative Stress ◽

Neurological Diseases ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

The Novel ◽

Systemic Delivery ◽

Neuroprotective Effects

Intracortical microelectrodes are valuable tools used to study and treat neurological diseases. Due in large part to the oxidative stress and inflammatory response occurring after electrode implantation, the signal quality of these electrodes decreases over time. To alleviate this response, resveratrol, a natural antioxidant which elicits neuroprotective effects through reduction of oxidative stress, was utilized. This work compares traditional systemic delivery of resveratrol to the novel cyclodextrin polymer (pCD) local delivery approach presented herein, both in vitro and in vivo. The pCD displayed an extended resveratrol release for 100 days, as well as 60 days of free radical scavenging activity in vitro. In vivo results indicated that our pCD delivery system successfully delivered resveratrol to the brain with a sustained release for the entire short-duration study (up to 7 days). Interestingly, significantly greater concentrations of resveratrol metabolites were found at the intracortical probe implantation site compared to the systemic administration of resveratrol. Together, our pilot results provide support for the possibility of improving the delivery of resveratrol in an attempt to stabilize long-term neural interfacing applications.

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Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview

Antioxidants ◽

10.3390/antiox10040507 ◽

2021 ◽

Vol 10 (4) ◽

pp. 507

Author(s):

Rosaria Meccariello ◽

Stefania D’Angelo

Keyword(s):

Oxidative Stress ◽

Food Sources ◽

Preventive Action ◽

Nutritional Interventions ◽

Beneficial Effects ◽

Age Related ◽

Macromolecular Damage ◽

And Oxidative Stress

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.

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Fighting Liver Fibrosis with Naturally Occurring Antioxidants

Planta Medica ◽

10.1055/a-0757-0008 ◽

2018 ◽

Vol 84 (18) ◽

pp. 1318-1333 ◽

Cited By ~ 3

Author(s):

Ligen Lin ◽

Fayang Zhou ◽

Shengnan Shen ◽

Tian Zhang

Keyword(s):

Oxidative Stress ◽

Liver Fibrosis ◽

Normal Liver ◽

Natural Antioxidants ◽

In Vivo Studies ◽

Lead Compounds ◽

Naturally Occurring ◽

Wound Healing Response

AbstractLiver fibrosis is a wound-healing response characterized by the accumulation of extracellular matrix following various liver injuries, which results in the deformation of the normal liver architecture and the development of liver cirrhosis and even hepatocellular carcinoma. Numerous in vitro and in vivo studies indicated that oxidative stress mediates the initiation and progression of liver fibrosis. Overaccumulation of reactive oxygen species disrupts macromolecules, induces necrosis and apoptosis of hepatocytes, stimulates the production of pro-fibrogenic mediators, and directly activates hepatic stellate cells, thereby resulting in liver damage and initiating liver fibrosis. Ameliorating oxidative stress is a potential therapeutic strategy for the treatment of liver fibrosis. Natural antioxidants have attracted increasing attention in treating liver fibrosis due to their safety and efficacy. In this review, the pathogenesis of liver fibrosis and the role of oxidative stress in liver fibrosis were discussed. Naturally occurring antioxidants that can treat and prevent liver fibrosis were summarized. Advances in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of oxidative stress in liver fibrosis to representative antioxidants for treating liver fibrosis. Naturally occurring antioxidants show a potential for further investigations as lead compounds in fighting liver fibrosis.

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The Neuroprotective Effects of Carvacrol on Ethanol-Induced Hippocampal Neurons Impairment via the Antioxidative and Antiapoptotic Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/4079425 ◽

2017 ◽

Vol 2017 ◽

pp. 1-17 ◽

Cited By ~ 8

Author(s):

Peng Wang ◽

Qian Luo ◽

Hui Qiao ◽

Hui Ding ◽

Yonggang Cao ◽

...

Keyword(s):

Oxidative Stress ◽

Western Blot ◽

Cognitive Dysfunction ◽

Hippocampal Neurons ◽

Morris Water Maze Test ◽

Oxidative Stress Biomarkers ◽

Neuroprotective Effects ◽

Stress Injury

Chronic alcohol consumption causes hippocampal neuronal impairment, which is associated with oxidative stress and apoptosis. Carvacrol is a major monoterpenic phenol found in essential oils from the family Labiatae and has antioxidative stress and antiapoptosis actions. However, the protective effects of carvacrol in ethanol-induced hippocampal neuronal impairment have not been fully understood. We explored the neuroprotective effects of carvacrol in vivo and in vitro. Male C57BL/6 mice were exposed to 35% ethanol for 4 weeks to establish ethanol model in vivo, and hippocampal neuron injury was simulated by 200 mM ethanol in vitro. Morris water maze test was performed to evaluate the cognitive dysfunction. The oxidative stress injury of hippocampal neurons was evaluated by measuring the levels of oxidative stress biomarkers. Histopathological examinations and western blot were performed to evaluate the apoptosis of neurons. The results showed that carvacrol attenuates the cognitive dysfunction, oxidative stress, and apoptosis of the mice treated with ethanol and decreases hippocampal neurons apoptosis induced by ethanol in vitro. In addition, western blot analysis revealed that carvacrol modulates the protein expression of Bcl-2, Bax, caspase-3, and p-ERK, without influence of p-JNK and p-p38. Our results suggest that carvacrol alleviates ethanol-mediated hippocampal neuronal impairment by antioxidative and antiapoptotic effects.

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Brazilian Green Propolis Protects against Retinal Damage In Vitro and In Vivo

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nek005 ◽

2006 ◽

Vol 3 (1) ◽

pp. 71-77 ◽

Cited By ~ 41

Author(s):

Yuta Inokuchi ◽

Masamitsu Shimazawa ◽

Yoshimi Nakajima ◽

Shinsuke Suemori ◽

Satoshi Mishima ◽

...

Keyword(s):

Oxidative Stress ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Water Soluble ◽

Retinal Damage ◽

Retinal Ganglion ◽

Neuroprotective Effects ◽

Brazilian Green Propolis

Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory) effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retinain vitroand/orin vivo.In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2) exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin–reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus) by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation), as also did trolox (water-soluble vitamin E). In micein vivo, propolis (100 mg kg−1; intraperitoneally administered four times) reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer) induced by intravitrealin vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage bothin vitroandin vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects.

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Food Derived Bioactive Peptides for Health Enhancement and Management of Some Chronic Diseases

Asian Food Science Journal ◽

10.9734/afsj/2019/v8i129981 ◽

2019 ◽

pp. 1-11

Author(s):

A. F. Ogori ◽

A. T. Girgih ◽

J. O. Abu ◽

M. O. Eke

Keyword(s):

Oxidative Stress ◽

Chronic Diseases ◽

Molecular Mechanisms ◽

Bioactive Peptides ◽

Food Sources ◽

In Vivo Studies ◽

Future Research ◽

Target Cells

The bioactive peptides produced by enzymatic hydrolysis, acid hydrolysis and fermentation approach have been identified and used widely in research. These methods are important in enhancement or prevention and management of chronic diseases that are ravaging the world such as type -2-diabetes, hypertension, oxidative stress, cancer, and obesity. Sources of bioactive peptides have been established ranging from plant to animal and marine foods that have pharmacological effects; however these effects are dependent on target cells and peptides structure and conformations. Plants such as hemp and animal source such as milk among others validate the findings of In vitro and In-vivo studies and the efficiency of these bioactive peptides in the management of certain chronic diseases. This article reviews the literature on bioactive peptides with concern on food sources, production and bioactive peptides application in enhancement of health and management of hypertension, diabetes and oxidative stress. Future research efforts on bioactive peptides should be directed towards elucidating specific sequenced bioactive peptides and their molecular mechanisms, through In-vivo and In-vitro studies for specific health condition in human using nutrigenomics and peptideomic approaches.

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Food Derived Bioactive Peptides for Health Enhancement and Management of Some Chronic Diseases

Asian Food Science Journal ◽

10.9734/afsj/2019/v8i130011 ◽

2019 ◽

pp. 1-11

Author(s):

A. F. Ogori ◽

A. T. Girgih ◽

J. O. Abu ◽

M. O. Eke

Keyword(s):

Oxidative Stress ◽

Chronic Diseases ◽

Molecular Mechanisms ◽

Bioactive Peptides ◽

Food Sources ◽

In Vivo Studies ◽

Future Research ◽

Target Cells

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Pursuing the Elixir of Life: In Vivo Antioxidative Effects of Manganosalen Complexes

Antioxidants ◽

10.3390/antiox9080727 ◽

2020 ◽

Vol 9 (8) ◽

pp. 727

Author(s):

Lara Rouco ◽

Ana M. González-Noya ◽

Rosa Pedrido ◽

Marcelino Maneiro

Keyword(s):

Tissue Injury ◽

Chemical Reactivity ◽

Natural Antioxidants ◽

Redox Balance ◽

In Vivo Studies ◽

Fetal Malformations ◽

Antioxidative Effects ◽

Stress Models

Manganosalen complexes are coordination compounds that possess a chelating salen-type ligand, a class of bis-Schiff bases obtained by condensation of salicylaldehyde and a diamine. They may act as catalytic antioxidants mimicking both the structure and the reactivity of the native antioxidant enzymes active site. Thus, manganosalen complexes have been shown to exhibit superoxide dismutase, catalase, and glutathione peroxidase activities, and they could potentially facilitate the scavenging of excess reactive oxygen species (ROS), thereby restoring the redox balance in damaged cells and organs. Initial catalytic studies compared the potency of these compounds as antioxidants in terms of rate constants of the chemical reactivity against ROS, giving catalytic values approaching and even exceeding that of the native antioxidative enzymes. Although most of these catalytic studies lack of biological relevance, subsequent in vitro studies have confirmed the efficiency of many manganosalen complexes in oxidative stress models. These synthetic catalytic scavengers, cheaper than natural antioxidants, have accordingly attracted intensive attention for the therapy of ROS-mediated injuries. The aim of this review is to focus on in vivo studies performed on manganosalen complexes and their activity on the treatment of several pathological disorders associated with oxidative damage. These disorders, ranging from the prevention of fetal malformations to the extension of lifespan, include neurodegenerative, inflammatory, and cardiovascular diseases; tissue injury; and other damages related to the liver, kidney, or lungs.

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Antioxidant Activity of Pigmented Rice and Impact on Health

JURNAL PANGAN ◽

10.33964/jp.v28i1.416 ◽

2019 ◽

Vol 28 (1) ◽

pp. 11-22

Author(s):

Arfina Sukmawati Arifin

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Antioxidant Activity ◽

Vascular Function ◽

Healthy Lifestyle ◽

Cell Damage ◽

The Body ◽

Food Sources

The high number of free radicals that are not balanced with the amount of antioxidants in the body triggers oxidative stress. Oxidative stress causes impaired vascular function, damage to proteins and lipids in membrane cell, and nucleic acid (DNA) mutations. Chronic cell damage has a negative effect on tissue that triggers various diseases such as neurodegenerative diseases (Alzheimer's, Parkinson's), cardiovascular diseases (hypertension, arteriosclerosis, and others), cataracts, retinal damage, maculopathy, rheumatoid arthritis, asthma, stroke, diabetes mellitus , immunodepression, cancer, aging, hyperoxia, dermatitis, and others. The application of a healthy lifestyle for example by consuming food sources of bioactive compounds can minimize health risks. Rice is the staple food of the Indonesian people. Some types of rice contain red and black pigments which are known to have high antioxidant activity compared to white rice. The pigment comes from anthocyanin and proanthocyanidin. Various studies in vitro and in vivo prove that anthocyanin and proantocyanidine act as antioxidants and potency as a preventative for various diseases such as cardiovascular, diabetes mellitus, and etc.

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The brain penetrant PPARγ agonist leriglitazone restores multiple altered pathways in models of X-linked adrenoleukodystrophy

Science Translational Medicine ◽

10.1126/scitranslmed.abc0555 ◽

2021 ◽

Vol 13 (596) ◽

pp. eabc0555

Author(s):

Laura Rodríguez-Pascau ◽

Anna Vilalta ◽

Marc Cerrada ◽

Estefania Traver ◽

Sonja Forss-Petter ◽

...

Keyword(s):

Oxidative Stress ◽

Spinal Cord ◽

Molecular Mechanisms ◽

Phase 1 ◽

Clinical Manifestations ◽

Neuroprotective Effects ◽

In Vivo Models ◽

Pparγ Agonist

X-linked adrenoleukodystrophy (X-ALD), a potentially fatal neurometabolic disorder with no effective pharmacological treatment, is characterized by clinical manifestations ranging from progressive spinal cord axonopathy [adrenomyeloneuropathy (AMN)] to severe demyelination and neuroinflammation (cerebral ALD-cALD), for which molecular mechanisms are not well known. Leriglitazone is a recently developed brain penetrant full PPARγ agonist that could modulate multiple biological pathways relevant for neuroinflammatory and neurodegenerative diseases, and particularly for X-ALD. We found that leriglitazone decreased oxidative stress, increased adenosine 5′-triphosphate concentration, and exerted neuroprotective effects in primary rodent neurons and astrocytes after very long chain fatty acid–induced toxicity simulating X-ALD. In addition, leriglitazone improved motor function; restored markers of oxidative stress, mitochondrial function, and inflammation in spinal cord tissues from AMN mouse models; and decreased the neurological disability in the EAE neuroinflammatory mouse model. X-ALD monocyte–derived patient macrophages treated with leriglitazone were less skewed toward an inflammatory phenotype, and the adhesion of human X-ALD monocytes to brain endothelial cells decreased after treatment, suggesting the potential of leriglitazone to prevent the progression to pathologically disrupted blood-brain barrier. Leriglitazone increased myelin debris clearance in vitro and increased myelination and oligodendrocyte survival in demyelination-remyelination in vivo models, thus promoting remyelination. Last, leriglitazone was clinically tested in a phase 1 study showing central nervous system target engagement (adiponectin increase) and changes on inflammatory biomarkers in plasma and cerebrospinal fluid. The results of our study support the use of leriglitazone in X-ALD and, more generally, in other neuroinflammatory and neurodegenerative conditions.

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