Biological activities of astaxanthin in the treatment of neurodegenerative diseases

Dang Y., Li Z., Yu F.

In recent years, astaxanthin as a natural substance has received widespread attention for its potential to replace traditional synthetic antioxidants and because its antioxidant activity exceeds that of similar substances. Based on this, this review introduces the specific forms of astaxanthin currently used as an antioxidant in foods, both in its naturally occurring forms and in artificially added forms involving technologies such as emulsion, microcapsule, film, nano liposome and nano particle, aiming to improve its stability, dispersion and bioavailability in complex food systems. In addition, research progress on the application of astaxanthin in various food products, such as whole grains, seafood and poultry products, is summarized. In view of the characteristics of astaxanthin, such as insolubility in water and sensitivity to light, heat, oxygen and humidity, the main research trends of astaxanthin-loaded systems with high encapsulation efficiency, good stability, good taste masking effect and cost-effectiveness are also pointed out. Finally, the possible sensory effects of adding astaxanthin to food aresummarized, providing theoretical support for the development of astaxanthin-related food.

Gu Z., Zhao H., Song Y., Kou Y., Yang W., Li Y., Li X., Ding L., Sun Z., Lin J., Wang Q., Li X., Yang X., Huang X., Yang C., et. al.

Alzheimer’s disease (AD), which is a prevailing type of dementia, presents a significant global health concern. The current therapies do not meet clinical expectations. Amyloid-beta (Aβ) has been found to induce endogenous formaldehyde (FA) accumulation by inactivating FA dehydrogenase (FDH); in turn, excessive FA triggers Aβ aggregation that eventually leads to AD onset. Hence, scavenging FA by astaxanthin (ATX, a strong exogenous antioxidant) may be pursued as a promising disease-modifying approach. Here, we report that liposomal nanoparticles coupled with PEG (PEG-ATX@NPs) could enhance water-solubility of ATX and alleviate cognitive impairments by scavenging FA and reducing Aβ deposition. To enable drug delivery to the brain, liposomes were used to encapsulate ATX and then coupled with PEG, which produced liposomal nanoparticles (PEGATX@NPs) with a diameter of

Liu N., Lyu X., Zhang X., Zhang F., Chen Y., Li G.

Abstract Objective Oxidative stress plays a pivotal role in neurodegenerative diseases. Astaxanthin (AST) can play a neuroprotective role owing to its long-chain conjugated unsaturated double bond, which imparts potent antioxidant, anti-neuroinflammatory, and anti-apoptotic properties. However, the biological mechanisms underlying these effects remain unknown. Therefore, this study aimed to investigate and validate the protective effect of AST on neuronal senescence and apoptosis caused by oxidative stress induced by Aβ25–35 peptide, with the goal of preventing the onset of cognitive dysfunction. Methods Alzheimer's disease models comprising ICR mice and PC12 cells were established using Aβ25–35. The Morris water maze test was used to assess mouse behavior. Nissl staining revealed morphological changes in the mouse hippocampal neurons. To elucidate the mechanism of action of AST, ICR mice and PC12 cells were treated with the silent information regulator 1 (SIRT1) inhibitor nicotinamide (NAM). Additionally, immunofluorescence, western blotting, and reverse transcription polymerase chain reaction were used to evaluate changes in the expression of Bcl-2 and Bax in the mouse hippocampus, and SIRT1/PGC-1α signaling pathway proteins were detected. Moreover, the oxidative stress markers in ICR mice and PC12 cells were evaluated. Further, CCK-8 assays, Annexin V/PI double staining, and β-galactosidase activity assays were performed in PC12 cells to evaluate the anti-senescence and apoptotic effects of AST. Results In vivo experiments showed that Aβ25–35 impaired cognitive function, promoted morphological changes in hippocampal neurons, decreased Bcl-2 expression, increased Bax expression, decreased superoxide dismutase and GSH-px levels, and increased reactive oxygen species and malondialdehyde levels. Conversely, AST alleviated the impact of Aβ25–35 in mice, with reversed outcomes. NAM administration reduced SIRT1 and PGC-1α expression in the hippocampus. This decrease was accompanied by cognitive dysfunction and hippocampal neuron atrophy, which were also evident in the mice. Additionally, in vitro experiments showed that Aβ25–35 could promote oxidative stress and induce the senescence and apoptosis of PC12 cells. Nonetheless, AST treatment counteracted this effect by inhibiting oxidative stress and altering the state of PC12 cells. Notably, the Aβ + NAM group exhibited the most significant rates of senescence and apoptosis in PC12 cells following NAM treatment. Conclusion AST can improve cellular senescence and apoptosis mediated by oxidative stress via the SIRT1/PGC-1α signaling pathway and plays a vital role in inhibiting neuronal senescence and apoptosis and enhancing cognitive ability.

Shehata M.K., Ismail A.A., Kamel M.A.

Zaib S., Javed H., Khan I., Jaber F., Sohail A., Zaib Z., Mehboob T., Tabassam N., Ogaly H.A.

AbstractNeurodegenerative diseases are a group of diseases with several neuropathological symptoms. Degenerative nerve diseases can be serious or life‐threatening. Because of the rise in the older population in recent years, these age‐dependent diseases are becoming more and more common. The WHO reports that within a few years, neurodegenerative diseases will overtake cancer to become the second leading cause of fatalities with cardiovascular diseases being the first. All neurodegenerative diseases have a common ground in that they are all associated with some sort of gene mutation leading to subsequent protein dysfunction. This review focuses on 6 neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy, spinocerebellar ataxia, and prions disease. The study aims to provide a basic understanding of the onset, epidemiology, causes, and role of associated proteins of the neurodegenerative diseases and will also go over any treatments which are currently being employed for the specific diseases. This presented data will allow to establish a slight comparison between the mentioned diseases and highlight any similarities and dissimilarities they may possess, thus providing the scientific community with basic knowledge on these diseases to help future research.

Shehata M.K., Ismail A.A., Kamel M.A.

Onohuean H., Akiyode A.O., Akiyode O., Igbinoba S.I., Alagbonsi A.I.

IntroductionThere is a scarcity of epidemiological data on neurodegenerative diseases (NDs) in East Africa. This meta-analysis provides the regional prevalence of NDs, their contributing factors, and evidence of change over time concerning gender per age or year.MethodsArticles were retrieved from electronic databases following the PRISMA standard.ResultsForty-two studies were reviewed, and 25 were meta-analyzed with a random-effects model. The pool estimate proportion of 15.27%, 95% CI (0.09–0.23) (I2 = 98.25%), (Q = 1,369.15, p < 0.0001) among a population of 15,813 male/female and 1,257 with NDs. Epidemiological characteristics associated with NDs include Dyskinesias prevalence 55.4%, 95% CI (13.5; 90.9), I2 (96%) and subsistence farming prevalence 11.3%, 95% CI (5.8; 20.9), I2 (99%). Publication bias by Egger test was (z = 4.1913, p < 0.0001), while rank correlation test using Kendall's model was (tau = 0.1237, p = 0.3873). Heterogeneity (R2 design = 5.23%, p design < 0.0001; R2 size = 52.163%, p size < 0.001; and R2 period = 48.13, p period < 0.0001. Covariates (R2 design + size + period = 48.41%, p < 0.001).ConclusionThere is a high prevalence of NDs in the East African region, which could impact life expectancy, morbidity, and quality of life. Thus, early screening and regular surveillance could assist in management strategies.

Kim S., Chen J., Cheng T., Gindulyte A., He J., He S., Li Q., Shoemaker B.A., Thiessen P.A., Yu B., Zaslavsky L., Zhang J., Bolton E.E.

Abstract PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves a wide range of use cases. In the past two years, a number of changes were made to PubChem. Data from more than 120 data sources was added to PubChem. Some major highlights include: the integration of Google Patents data into PubChem, which greatly expanded the coverage of the PubChem Patent data collection; the creation of the Cell Line and Taxonomy data collections, which provide quick and easy access to chemical information for a given cell line and taxon, respectively; and the update of the bioassay data model. In addition, new functionalities were added to the PubChem programmatic access protocols, PUG-REST and PUG-View, including support for target-centric data download for a given protein, gene, pathway, cell line, and taxon and the addition of the ‘standardize’ option to PUG-REST, which returns the standardized form of an input chemical structure. A significant update was also made to PubChemRDF. The present paper provides an overview of these changes.

Wang S., Qi X.

Neuroinflammation is a protective mechanism against insults from exogenous pathogens and endogenous cellular debris and is essential for reestablishing homeostasis in the brain. However, excessive prolonged neuroinflammation inevitably leads to lesions and disease. The use of natural compounds targeting pathways involved in neuroinflammation remains a promising strategy for treating different neurological and neurodegenerative diseases. Astaxanthin, a natural xanthophyll carotenoid, is a well known antioxidant. Mounting evidence has revealed that astaxanthin is neuroprotective and has therapeutic potential by inhibiting neuroinflammation, however, its functional roles and underlying mechanisms in modulating neuroinflammation have not been systematically summarized. Hence, this review summarizes recent progress in this field and provides an update on the medical value of astaxanthin. Astaxanthin modulates neuroinflammation by alleviating oxidative stress, reducing the production of neuroinflammatory factors, inhibiting peripheral inflammation and maintaining the integrity of the blood-brain barrier. Mechanistically, astaxanthin scavenges radicals, triggers the Nrf2-induced activation of the antioxidant system, and suppresses the activation of the NF-κB and mitogen-activated protein kinase pathways. With its good biosafety and high bioavailability, astaxanthin has strong potential for modulating neuroinflammation, although some outstanding issues still require further investigation.

Cano A., Fonseca E., Ettcheto M., Sánchez-López E., de Rojas I., Alonso-Lana S., Morató X., Souto E.B., Toledo M., Boada M., Marquié M., Ruíz A.

Epilepsy is a chronic disease of the central nervous system characterized by an electrical imbalance in neurons. It is the second most prevalent neurological disease, with 50 million people affected around the world, and 30% of all epilepsies do not respond to available treatments. Currently, the main hypothesis about the molecular processes that trigger epileptic seizures and promote the neurotoxic effects that lead to cell death focuses on the exacerbation of the glutamate pathway and the massive influx of Ca2+ into neurons by different factors. However, other mechanisms have been proposed, and most of them have also been described in other neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, or multiple sclerosis. Interestingly, and mainly because of these common molecular links and the lack of effective treatments for these diseases, some antiseizure drugs have been investigated to evaluate their therapeutic potential in these pathologies. Therefore, in this review, we thoroughly investigate the common molecular pathways between epilepsy and the major neurodegenerative diseases, examine the incidence of epilepsy in these populations, and explore the use of current and innovative antiseizure drugs in the treatment of refractory epilepsy and other neurodegenerative diseases.

Singh A., Dawson T.M., Kulkarni S.

Neurodegenerative disorders (NDs) affect essential functions not only in the CNS, but also cause persistent gut dysfunctions, suggesting that they have an impact on both CNS and gut-innervating neurons. Although the CNS biology of NDs continues to be well studied, how gut-innervating neurons, including those that connect the gut to the brain, are affected by or involved in the etiology of these debilitating and progressive disorders has been understudied. Studies in recent years have shown how CNS and gut biology, aided by the gut-brain connecting neurons, modulate each other's functions. These studies underscore the importance of exploring the gut-innervating and gut-brain connecting neurons of the CNS and gut function in health, as well as the etiology and progression of dysfunction in NDs. In this Review, we discuss our current understanding of how the various gut-innervating neurons and gut physiology are involved in the etiology of NDs, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, to cause progressive CNS and persistent gut dysfunction.

Balendra V., Singh S.K.

Oxidative stress, the imbalance of the antioxidant system, results in an accumulation of neurotoxic proteins in Alzheimer's disease (AD). The antioxidant system is composed of exogenous and endogenous antioxidants to maintain homeostasis. Superoxide dismutase (SOD) is an endogenous enzymatic antioxidant that converts superoxide ions to hydrogen peroxide in cells. SOD supplementation in mice prevented cognitive decline in stress-induced cells by reducing lipid peroxidation and maintaining neurogenesis in the hippocampus. Furthermore, SOD decreased expression of BACE1 while reducing plaque burden in the brain. Additionally, Astaxanthin (AST), a potent exogenous carotenoid, scavenges superoxide anion radicals. Mice treated with AST showed slower memory decline and decreased depositions of amyloid-beta (A β ) and tau protein. Currently, the neuroprotective potential of these supplements has only been examined separately in studies. However, a single antioxidant cannot sufficiently resist oxidative damage to the brain, therefore, a combinatory approach is proposed as a relevant therapy for ameliorating pathological changes in AD.

Rai S.N., Mishra D., Singh P., Vamanu E., Singh M.P.

Neurodegenerative diseases (NDs) represent a common neurological pathology that determines a progressive deterioration of the brain or the nervous system. For treating NDs, comprehensive and alternative medicines have attracted scientific researchers' attention recently. Edible mushrooms are essential for preventing several age-based neuronal dysfunctions such as Parkinson's and Alzheimer's diseases. Mushroom such as Grifola frondosa , Lignosus rhinocerotis , Hericium erinaceus, may improve cognitive functions. It has also been reported that edible mushrooms (basidiocarps/mycelia extracts or isolated bioactive compounds) may reduce beta-amyloid-induced neurotoxicity. Medicinal mushrooms are being used for novel and natural compounds that help modulate immune responses and possess anti-cancer, anti-microbial, and anti-oxidant properties. Compounds such as polyphenols, terpenoids, alkaloids, sesquiterpenes, polysaccharides, and metal chelating agents are validated in different ND treatments. This review aims to assess mushrooms' role and their biomolecules utilization for treating different kinds of NDs. The action mechanisms, presented here, including reducing oxidative stress, neuroinflammation, and modulation of acetylcholinesterase activity, protecting neurons or stimulation, and regulating neurotrophins synthesis. We also provide background about neurodegenerative diseases and in-silico techniques of the drug research. High costs associated with experiments and current ethical law imply efficient alternatives with limited cost value. In silico approaches provide an alternative method with low cost that has been successfully implemented to cure ND disorders in recent days. We also describe the applications of computational procedures such as molecular docking, virtual high-throughput screening, molecular dynamic (MD) simulation, quantum-mechanical methods for drug design. They were reported against various targets in NDs. • Edible mushrooms show very potent Anti-oxidative and Anti-inflammatory activity. • Biomolecules of mushrooms show a prominent therapeutic response against lifestyle-related diseases. • Mushrooms also widely utilize to manage neurodegenerative diseases like Parkinson’s and Alzheimer’s disease. • The biomolecules of mushrooms also exhibit strong therapeutic properties. • Insilco approach is utilized to investigate the characterizes the important bioactive constituent in mushrooms.

Binatti E., Zoccatelli G., Zanoni F., Donà G., Mainente F., Chignola R.

Radiation-induced fibrosis is a serious long-lasting side effect of radiation therapy. Central to this condition is the role of macrophages that, activated by radiation-induced reactive oxygen species and tissue cell damage, produce pro-inflammatory cytokines, such as transforming growth factor beta (TGFβ). This, in turn, recruits fibroblasts at the site of the lesion that initiates fibrosis. We investigated whether astaxanthin, an antioxidant molecule extracted from marine and freshwater organisms, could help control macrophage activation. To this purpose, we encapsulated food-grade astaxanthin from Haematococcus pluvialis into micrometer-sized whey protein particles to specifically target macrophages that can uptake material within this size range by phagocytosis. The data show that astaxanthin-loaded microparticles are resistant to radiation, are well-tolerated by J774A.1 macrophages, induce in these cells a significant reduction of intracellular reactive oxygen species and inhibit the release of active TGFβ as evaluated in a bioassay with transformed MFB-F11 fibroblasts. Micro-encapsulation of bioactive molecules is a promising strategy to specifically target phagocytic cells and modulate their own functions.

McCarty M.F., Lerner A.

Introduction: Ischemic stroke and traumatic brain injury are leading causes of acute mortality, and in the longer run, major causes of significant mental and physical impairment. Most of the brain neuronal cell death in the minutes and hours following an ischemic stroke or brain trauma is mediated by the process of excitotoxicity, in which sustained elevations of extracellular glutamate, reflecting a failure of ATP-dependent mechanism which sequester glutamate in neurons and astrocytes, drive excessive activation of NMDA receptors. Areas covered: A literature search was undertaken to clarify the molecular mechanisms whereby excessive NMDA activation leads to excitotoxic neuronal death, and to determine what safe nutraceutical agents might have practical potential for rescuing at-risk neurons by intervening in these mechanisms. Expert opinion: Activation of both NADPH oxidase and neuronal nitric oxide synthase in the microenvironment of activated NMDA receptors drives production of superoxide and highly toxic peroxynitrite. This leads to excessive activation of PARP and p38 MAP kinase, mitochondrial dysfunction, and subsequent neuronal death. Heme oxygenase-1 (HO-1) induction offers protection via inhibition of NADPH oxidase and promotion of cGMP generation. Phase 2-inductive nutraceuticals can induce HO-1, and other nutraceuticals can mimic the effects of its products biliverdin and carbon monoxide.

Yu Q., Li Y., Yu J., Gao J.