astaxanthine and Neurodegenerative-Diseases

Astaxanthin is a natural C40 carotenoid with numerous reported biological functions, most of them associated with its antioxidant and anti-inflammatory activity, standing out from other antioxidants as it has shown the highest oxygen radical absorbance capacity (ORAC), 100-500 times higher than ⍺-tocopherol and a 10 times higher free radical inhibitory activity than related antioxidants (α-tocopherol, α-carotene, β -carotene, lutein and lycopene). In vitro and in vivo studies have associated astaxanthin's unique molecular features with several health benefits, including neuroprotective, cardioprotective and antitumoral properties, suggesting its therapeutic potential for the prevention or co-treatment of dementia, Alzheimer, Parkinson, cardiovascular diseases and cancer. Benefits on skin and eye health promotion have also been reported, highlighting its potential for the prevention of skin photo-aging and the treatment of eye diseases like glaucoma, cataracts and uveitis. In this review, we summarize and discuss the currently available evidence on astaxanthin benefits, with a particular focus on human clinical trials, including a brief description of the potential mechanisms of action responsible for its biological activities.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cardiovascular Diseases; Clinical Trials as Topic; Drug Development; Drug Discovery; Humans; Neoplasms; Neurodegenerative Diseases; Xanthophylls

The complex pathophysiological mechanisms behind destructive chronic conditions, including cancer, neurodegenerative diseases, diabetes mellitus, cardiovascular diseases, and hepatic failure urge the need for finding related pivotal dysregulated signaling mediators, as well as multi-target therapeutic agents. In the current study, critical roles of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, as potential therapeutic targets in the pathogenesis of various diseases has been described. This pathway is also interconnected with several downstream inflammatory, oxidative stress, and apoptotic mediators, as dysregulated pathways in chronic diseases. Therefore, identifying novel multi-target agents to attenuate PI3K/Akt, thereby related downstream pathways, is of great importance. Astaxanthin (AST) is a multi-target lipid-soluble keto-carotenoid derived from the varieties of marine organisms, with potential anti-inflammatory, antioxidant and antiapoptotic properties through PI3K/Akt pathway. Nowadays, due to its high nutritional and medicinal value, research on AST is increasing. This review aimed to address PI3K/Akt targeted by AST in several diseases toward clinical applications.

Topics: Animals; Diabetes Mellitus; Humans; Neoplasms; Neurodegenerative Diseases; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Signal Transduction; Xanthophylls

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.

Topics: Aging; Animals; Drug Delivery Systems; Humans; Nanoparticles; Neurodegenerative Diseases; Neuroprotective Agents; Structure-Activity Relationship; Theranostic Nanomedicine; Xanthophylls

Astaxanthin is a carotenoid with powerful antioxidant and anti-inflammatory activity produced by several freshwater and marine microorganisms, including bacteria, yeast, fungi, and microalgae. Due to its deep red-orange color it confers a reddish hue to the flesh of salmon, shrimps, lobsters, and crayfish that feed on astaxanthin-producing organisms, which helps protect their immune system and increase their fertility. From the nutritional point of view, astaxanthin is considered one of the strongest antioxidants in nature, due to its high scavenging potential of free radicals in the human body. Recently, astaxanthin is also receiving attention for its effect on the prevention or co-treatment of neurological pathologies, including Alzheimer and Parkinson diseases. In this review, we focus on the neuroprotective properties of astaxanthin and explore the underlying mechanisms to counteract neurological diseases, mainly based on its capability to cross the blood-brain barrier and its oxidative, anti-inflammatory, and anti-apoptotic properties.

Topics: Anti-Inflammatory Agents; Apoptosis; Aquatic Organisms; Blood-Brain Barrier; Brain; Free Radical Scavengers; Free Radicals; Humans; Neurodegenerative Diseases; Neuroprotective Agents; Oxidation-Reduction; Xanthophylls

Since the industrial revolution, the consumption of processed food increased dramatically. During processing, food material loses many of its natural properties.. The simple restoration of the original properties of the processed food as well as fortification require food supplementation with compounds prepared chemically or of natural origin. The observations that natural food additives are safer and better accepted by consumers than synthetic ones have strongly increased the demand for natural compounds. Because some of them have only a low abundance or are even rare, their market price can be very high. This is the case for most carotenoids of natural origin to which this review is dedicated. The increasing demand for food additives of natural origin contributes to an accelerated depletion of traditional natural resources already threatened by intensive agriculture and pollution. To overcome these difficulties and satisfy the demand, alternative sources for natural carotenoids have to be found. In this context, photosynthetic microalgae present a very high potential because they contain carotenoids and are able to produce particular carotenoids under stress. Their potential also resides in the fact that only ten thousands of microalgal strains have been described while hundred thousands of species are predicted to exist. Carotenoids have been known for ages for their antioxidant and coloring properties, and a large body of evidence has been accumulated about their health potential.. This review summarizes both the medicinal and food industry applications of microalgae with emphasis on the former. In addition, traditional and alternative microalgal sources used for industrial carotenoid extraction, the chemical and physical properties, the biosynthesis and the localization of carotenoids in algae are also briefly discussed.

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Cardiovascular Diseases; Carotenoids; Food Coloring Agents; Microalgae; Neoplasms; Neurodegenerative Diseases; Xanthophylls

Astaxanthin (AXT) is a carotenoid with multiple health benefits. It is currently marketed as a health supplement and is well known for its antioxidant capacity. Recent evidence has emerged to suggest a broad range of biological activities. The interest in this compound has increased dramatically over the last few years and many studies are now applying this molecule across many disease models. Results from the current research are beginning to come together to suggest neuroprotective properties including anti-inflammatory, anti-apoptotic, and antioxidant effects, as well as the potential to promote or maintain neural plasticity. These emergent mechanisms of actions implicate AXT as a promising therapeutic agent for neurodegenerative disease. This review will examine and extrapolate from the recent literature to build support for the use of AXT in mitigating neuropathy in normal aging and neurodegenerative disease.

Topics: Aging; Animals; Dietary Supplements; Humans; Neurodegenerative Diseases; Neuroprotection; Neuroprotective Agents; Prognosis; Risk Assessment; Treatment Outcome; Xanthophylls

The consumption of marine fishes and general seafood has long been recommended by several medical authorities as a long-term nutritional intervention to preserve mental health, hinder neurodegenerative processes, and sustain cognitive capacities in humans. Most of the neurological benefits provided by frequent seafood consumption comes from adequate uptake of omega-3 and omega-6 polyunsaturated fatty acids, n-3/n-6 PUFAs, and antioxidants. Optimal n-3/n-6 PUFAs ratios allow efficient inflammatory responses that prevent the initiation and progression of many neurological disorders. Moreover, interesting in vivo and clinical studies with the marine antioxidant carotenoid astaxanthin (present in salmon, shrimp, and lobster) have shown promising results against free radical-promoted neurodegenerative processes and cognition loss. This review presents the state-of-the-art applications of n-3/n-6 PUFAs and astaxanthin as nutraceuticals against neurodegenerative diseases associated with exacerbated oxidative stress in CNS. The fundamental "neurohormesis" principle is discussed throughout this paper. Finally, new perspectives for the application of a natural combination of the aforementioned anti-inflammatory and antioxidant agents (found in krill oil) are also presented herewith.

Topics: Animals; Brain; Dietary Supplements; Disease Models, Animal; Euphausiacea; Fatty Acids, Omega-3; Fish Oils; Humans; Neurodegenerative Diseases; Neuroprotective Agents; Observational Studies as Topic; Oxidation-Reduction; Oxidative Stress; Shellfish; Xanthophylls

The carotenoid pigment astaxanthin has important applications in the nutraceutical, cosmetics, food and feed industries. Haematococcus pluvialis is the richest source of natural astaxanthin and is now cultivated at industrial scale. Astaxanthin is a strong coloring agent and a potent antioxidant - its strong antioxidant activity points to its potential to target several health conditions. This article covers the antioxidant, UV-light protection, anti-inflammatory and other properties of astaxanthin and its possible role in many human health problems. The research reviewed supports the assumption that protecting body tissues from oxidative damage with daily ingestion of natural astaxanthin might be a practical and beneficial strategy in health management.

Topics: Adjuvants, Immunologic; Administration, Oral; Antioxidants; Arteriosclerosis; beta Carotene; Biological Availability; Blindness; Chlorophyta; Diet Therapy; Humans; Inflammation; Macular Degeneration; Neoplasms; Neurodegenerative Diseases; Nutritional Physiological Phenomena; Photosensitivity Disorders; Radiation-Sensitizing Agents; Species Specificity; Xanthophylls

Excitotoxicity is known to associate with neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Huntington's disease, as well as aging, stroke, trauma, ischemia and epilepsy. Excessive release of glutamate, overactivation of glutamate receptors, calcium overload, mitochondrial dysfunction and excessive reactive oxygen species (ROS) formation are a few of the suggested key mechanisms. Astaxanthin (AST), a carotenoid, is known to act as an antioxidant and protect neurons from excitotoxic injuries. However, the exact molecular mechanism of AST neuroprotection is not clear. Thus, in this study, we investigated the role of AST in neuroprotection in excitotoxicity. We utilized primary cortical neuronal culture and live cell fluorescence imaging for the study. Our results suggest that AST prevents neuronal death, reduces ROS formation and decreases the abnormal mitochondrial membrane depolarization induced by excitotoxic glutamate insult. Additionally, AST modulates intracellular calcium levels by inhibiting peak and irreversible secondary sustained calcium levels in neurons. Furthermore, AST regulates the ionotropic glutamate subtype receptors NMDA, AMPA, KA and mitochondrial calcium. Moreover, AST decreases NMDA and AMPA receptor protein expression levels, while KA remains unaffected. Overall, our results indicate that AST protects neurons from excitotoxic neuronal injury by regulating ionotropic glutamate receptors, cytosolic secondary calcium rise and mitochondrial calcium buffering. Hence, AST could be a promising therapeutic agent against excitotoxic insults in neurodegenerative diseases.

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Antioxidants; Calcium; Glutamic Acid; Humans; Mitochondria; N-Methylaspartate; Neurodegenerative Diseases; Neurons; Reactive Oxygen Species; Receptors, AMPA; Receptors, Glutamate; Xanthophylls

The incidence of neurodegenerative disorders and cognitive impairment is increasing. Rising prevalence of age-related medical conditions is associated with a dramatic economic burden; therefore, developing strategies to manage these health concerns is of great public health interest. Nutritionally based interventions have shown promise in treatment of these age-associated conditions. Astaxanthin is a carotenoid with reputed neuroprotective properties in the context of disease and injury, while emerging evidence suggests that astaxanthin may also have additional biological activities relating to neurogenesis and synaptic plasticity. Here, we investigate the potential for astaxanthin to modulate cognitive function and neural plasticity in young and aged mice. We show that feeding astaxanthin to aged mice for 1 month improves performance on several hippocampal-dependent cognitive tasks and increases long-term potentiation. However, we did not observe an alteration in neurogenesis, nor did we observe a change in microglial-associated IBA1 immunostaining. This demonstrates the potential for astaxanthin to modulate neural plasticity and cognitive function in aging.

Topics: Aging; Animals; Behavior, Animal; Cognition; Cognitive Dysfunction; Dietary Supplements; Hippocampus; Inflammation; Long-Term Potentiation; Male; Mice; Mice, Inbred C57BL; Microglia; Neurodegenerative Diseases; Neurogenesis; Neuronal Plasticity; Neuroprotective Agents; Xanthophylls

Nerve growth factor differentiated PC12 cells were used to examine the antioxidative and anti-inflammatory effects of astaxanthin (AX) and canthaxanthin (CX). PC12 cells were pretreated with AX or CX at 10 or 20 muM, and followed by exposure of hydrogen peroxide (H(2)O(2)) or 1-methyl-4-phenylpyridinium ion (MPP(+)) to induce cell injury. H(2)O(2) or MPP(+) treatment significantly decreased cell viability, increased lactate dehydrogenase (LDH) release, enhanced DNA fragmentation, and lowered mitochondrial membrane potential (MMP) (P < 0.05). The pretreatments from AX or CX concentration-dependently alleviated H(2)O(2) or MPP(+)-induced cell death, LDH release, DNA fragmentation, and MMP reduction (P < 0.05). Either H(2)O(2) or MPP(+) treatment significantly increased malonyldialdehyde (MDA) and reactive oxygen species (ROS) formations, decreased glutathione content, and lowered glutathione peroxidase (GPX) and catalase activities (P < 0.05). The pretreatments from AX or CX significantly retained GPX and catalase activities, and decreased MDA and ROS formations (P < 0.05). H(2)O(2) or MPP(+) treatment significantly decreased Na(+)-K(+)-ATPase activity, elevated caspase-3 activity and levels of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha (P < 0.05); and the pretreatments from these agents significantly restored Na(+)-K(+)-ATPase activity, suppressed caspase-3 activity and release of IL-1, IL-6, and TNF-alpha (P < 0.05). Based on the observed antioxidative and anti-inflammatory protection from AX and CX, these 2 compounds were potent agents against neurodegenerative disorder.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Anti-Inflammatory Agents; Antioxidants; Canthaxanthin; Caspase 3; Cell Membrane; Cell Survival; Cytokines; DNA Fragmentation; Dose-Response Relationship, Drug; Hydrogen Peroxide; Membrane Potential, Mitochondrial; Nerve Growth Factor; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Oxidative Stress; PC12 Cells; Rats; Sodium-Potassium-Exchanging ATPase; Xanthophylls