• Nutrition Research and Practice
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• v.17 no.5
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• pp.899-916
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• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin's neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H₂O₂)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H₂O₂ (400 µM) in hesperetin absence or presence (10-40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4',6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H₂O₂-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H₂O₂-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF-κB translocation into H₂O₂-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H₂O₂-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention.

• Journal of the Korean Applied Science and Technology
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• v.35 no.1
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• pp.194-204
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• 2018

This study was to investigate the effect of the extract(KP-HE) from Kalopanax pictus(KP) fermented with Hericium erinaceum(HE) mycelium on oxidative modification of neurofilament-L(NF-L) which is closely related to neurodegenerative disorders. The oxidative modification of NF-L was induced by AAPH producing peroxyl radicals in solution, and KP, HE, and KP-HE was investigated. KP and HE did not protect NF-L against peroxyl radical-mediated NF-L modification whereas KP-HE significantly prevented NF-L modification induced by peroxyl radical. KP-HE inhibited the formation of dityrosine in oxidative modification of NF-L and stimulated the peroxyl radical scavenging activity. The effects of KP, HE, and KP-HE on the modification of NF-L by tetrahydropapaveroline(THP), a neurotoxin found in patients with Parkinson's disease was investigated. KP-HE also prevented THP-mediated NF-L modification as compared to KP and HE. In addition, KP-HE significantly inhibited the formation of dityrosine in oxidative modified NF-L and enhanced the inhibition of reactive oxygen species(ROS) was generated by THP. The results suggested that KP-HE can contribute to protected cell from oxidative stress was induced by ROS and neurotoxin. Therefore, KP-HE could potentially be used as a valuable functional food ingredient to prevent neurodegenerative disorders.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.8-29
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• 2013

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng's therapeutic effects. These include Alzheimer's disease, Parkinson's disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng.

• Sleep Medicine and Psychophysiology
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• v.29 no.2
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• pp.35-39
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• 2022

REM sleep behavior disorder is parasomnia characterized by unpleasant dreams and dream-enactment behaviors associated with excessive electromyography activity in REM sleep. This may appear idiopathic or secondary to other neurological or medical conditions. REM sleep behavior disorder, which appears to be idiopathic, most often implies the possibility of later neurodegenerative diseases due to synucleinopathy, so accurate diagnosis is important in predicting prognosis. For the diagnosis of REM sleep behavioral disorder, REM sleep without atonia, which appears in the polysomnography, is essential. Obstructive sleep apnea, trauma-related sleep disorders, and vigorous periodic leg movements during sleep are known as diseases that show dream enactment behavior in elderly patients. Considering that it may be accompanied by other sleep disorders that can mimic REM sleep behavioral disorders, it is important to differentiate sleep

• Journal of Life Science
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• v.32 no.1
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• pp.70-77
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• 2022

Endocrine disrupting chemicals (EDCs) have been attracting significant attention in modern society, owing to the increased incidence rate of various diseases along with population growth. EDCs are found in many commercial products, including some plastic bottles and containers, detergents, liners of metal food cans, flame retardants, food, toys, cosmetics, and pesticides. EDCs have a hormonal effect on the human body, which disrupts the endocrine system, notably affecting sexual differentiation and normal reproduction, and can trigger cancer as well. Recently, the association between neurological diseases and EDCs has become a hot topic of research in the field of neuroscience. Considering that EDCs negatively affect not only neuronal proliferation and neurotransmission but also the formation of the neuronal networks, EDCs may induce neurodevelopmental disorders, such as autism spectrum disorders and attention-deficit/hyperactivity disorder as well as neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. In light of these potentially deleterious outcomes, important efforts have been underway to minimize the exposure to EDCs through appropriate regulations and policies around the world, but chemicals that have not yet been associated with endocrine disrupting properties are still in wide use. Therefore, more epidemiological investigations and research are needed to fully understand the effects of EDCs on the nervous system.

• Natural Product Sciences
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• v.11 no.3
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• pp.174-178
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• 2005

Oxidative stress is an important causative factor in several human chronic diseases, such as atherosclerosis, cardiovascular disorders, mutagenesis, cancer, several neurodegenerative disorders, and the aging process. Phenolics and tannins are reported to be good antioxidants. Anogeissus latifolia (Combretaceae) bark has been used in the Indian traditional systems of medicine for curing a variety of ailments, but scientific validation is not available till date. Hence the present study was undertaken to isolate antioxidant compounds by activity-guided isolation. Inhibtion of diphenyl picryl hydrazyl (DPPH) and Xanthine oxidase along with photochemiluminescence assay were used as bioassay for antioxidant activity. Activity guided isolation was carried out using silica column and the compounds were quantified using HPLC. Ethyl acetate and butanol fraction exhibited potent antioxidant activity. Bioassay-guided isolation led to isolation of ellagic acid (1) and dimethyl ellagic acid (2) as the main active compounds, which along with gallic acid were quantified by HPLC. Thus we conclude that these three major tannoid principles present in A. latifolia, are responsible for the antioxidant potential and possibly their therapeutic potential.

• BMB Reports
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• v.48 no.4
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• pp.200-208
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• 2015

The field of redox proteomics focuses to a large extent on analyzing cysteine oxidation in proteins under different experimental conditions and states of diseases. The identification and localization of oxidized cysteines within the cellular milieu is critical for understanding the redox regulation of proteins under physiological and pathophysiological conditions, and it will in turn provide important information that are potentially useful for the development of novel strategies in the treatment and prevention of diseases associated with oxidative stress. Antioxidant enzymes that catalyze oxidation/reduction processes are able to serve as redox biomarkers in various human diseases, and they are key regulators controlling the redox state of functional proteins. Redox regulators with antioxidant properties related to active mediators, cellular organelles, and the surrounding environments are all connected within a network and are involved in diseases related to redox imbalance including cancer, ischemia/reperfusion injury, neurodegenerative diseases, as well as normal aging. In this review, we will briefly look at the selected aspects of oxidative thiol modification in antioxidant enzymes and thiol oxidation in proteins affected by redox control of antioxidant enzymes and their relation to disease. [BMB Reports 2015; 48(4): 200-208]

• Molecules and Cells
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• v.25 no.1
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• pp.7-19
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• 2008

Complexins play a critical role in the control of fast synchronous neurotransmitter release. They operate by binding to trimeric SNARE complexes consisting of the vesicle protein Synaptobrevin and the plasma membrane proteins Syntaxin and SNAP-25, which are key executors of membrane fusion reactions. SNARE complex binding by Complexins is thought to stabilize and clamp the SNARE complex in a highly fusogenic state, thereby providing a pool of readily releasable synaptic vesicles that can be released quickly and synchronously in response to an action potential and the concomitant increase in intra-synaptic $Ca^{2+}$ levels. Genetic elimination of Complexins from mammalian neurons causes a strong reduction in evoked neurotransmitter release, and altered Complexin expression levels with consequent deficits in synaptic transmission were suggested to contribute to the etiology or pathogenesis of schizophrenia, Huntington's disease, depression, bipolar disorder, Parkinson's disease, Alzheimer's disease, traumatic brain injury, Wernicke's encephalopathy, and fetal alcohol syndrome. In the present review I provide a summary of available data on the role of altered Complexin expression in brain diseases. On aggregate, the available information indicates that altered Complexin expression levels are unlikely to have a causal role in the etiology of the disorders that they have been implicated in, but that they may contribute to the corresponding symptoms.

• Journal of Society of Preventive Korean Medicine
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• v.15 no.2
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• pp.51-67
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• 2011

The average human life span has increased due to the development of modern medicine and science, resulting in prolonged life expectancy and increase in the population counts of the geriatric age group. In particular, a dramatic increase of elderly patients suffering from senile disorders including neurodegenerative diseases, Alzheimer's disease(AD), and vascular dementia has become a serious social problem in public health. Thus, this study is aimed to summarize available clinical trial data on several commonly used medicines include donepezil, rivastigmine, galantamine, memantine and oriental medicine, and examine the effect of oriental medicine combined with western medicine in the treatment of patients with senile disorders using the data from literature reviews and survey studies.

• BMB Reports
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• v.41 no.8
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• pp.560-567
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• 2008

The importance of lipids in cell signaling and tissue physiology is demonstrated by the many CNS pathologies involving deregulated lipid metabolism. One such critical metabolic event is the activation of phospholipase $A_2$ ($PLA_2$), which results in the hydrolysis of membrane phospholipids and the release of free fatty acids, including arachidonic acid, a precursor for essential cell-signaling eicosanoids. Reactive oxygen species (ROS, a product of arachidonic acid metabolism) react with cellular lipids to generate lipid peroxides, which are degraded to reactive aldehydes (oxidized phospholipid, 4-hydroxynonenal, and acrolein) that bind covalently to proteins, thereby altering their function and inducing cellular damage. Dissecting the contribution of $PLA_2$ to lipid peroxidation in CNS injury and disorders is a challenging proposition due to the multiple forms of $PLA_2$, the diverse sources of ROS, and the lack of specific $PLA_2$ inhibitors. In this review, we summarize the role of $PLA_2$ in CNS pathologies, including stroke, spinal cord injury, Alzheimer's, Parkinson's, Multiple sclerosis-Experimental autoimmune encephalomyelitis and Wallerian degeneration.