• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.3
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• pp.317-321
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• 2014

Amyloid-${\beta}$ protein ($A{\beta}$) is a pathological component of Alzheimer's disease (AD) by participating in the senile plaque formation in the patient's brain. Although the exact mechanism of $A{\beta}$ toxicity is not fully elucidated, it is considered to be closely related to its fibrillation process. For prevention of AD, recent studies have suggested various small molecules which inhibit $A{\beta}$ fibrillation. In this report, ${\beta}$-asarone found in acorus plant has been investigated as an anti-amyloid molecule. ${\beta}$-Asarone was demonstrated to prevent in vitro fibrillation of $A{\beta}$ by inducing the oligomer formation that obviously decreased cytotoxicity. Therefore, ${\beta}$-asarone could be suggested as an inhibitory agent of $A{\beta}$ fibrillation and toxicity, which would help us not only to understand underlying principle of amyloidogenesis mechanism but also to develop a controlling strategy toward AD.

• Journal of Mushroom
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• v.12 no.2
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• pp.77-81
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• 2014

Mushrooms are considered not only as food but also for source of physiologically beneficial medicines. The culinary-medicinal mushrooms may important role in the prevention of age-associated neurological dysfunctions, including Alzheimer's and Parkinson's diseases. Hericium erinaceus (H. erinaceus), is edible mushrooms, is a parasitic fungus that grows hanging off of logs and trees and well established candidate for brain and nerve health. H. erinaceus contains high amounts of antioxidants, beta-glucan, polysaccharides and a potent catalyst for brain tissue regeneration and helps to improve memory and cognitive functions. Its fruiting bodies and the fungal mycelia exhibit various pharmacological activities, including the enhancement of the immune system, antitumor, hypoglycemic and anti-aging properties. H. erinaceus stimulates the synthesis of Nerve Growth Factor (NGF) which is the primary protein nutrient responsible for enhancing and repairing neurological disorders. Especially hericenones and erinacines isolated from its fruitin body stimulate NGF, synthesis. This fungus is also utilized to regulate blood levels of glucose, triglycerides and cholesterol. H. erinaceus can be considered as useful therapeutic agents in the management and/or treatment of neurodegeneration diseases. However, this review focuses on in vitro, in vivo and clinical trials for neurodegerative disease.

• Journal of Oriental Neuropsychiatry
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• v.14 no.2
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• pp.95-105
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• 2003

Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the future AD will be the largest problem in public health service. From old times, Much medicines have been used for treatment of dementia, but there is no medicine having obvious effect. AD is one of brain retrogression disease. So We studied on herbal medicine that have a relation of brain retrogression. From old times, In Oriental Medicine, Radix Polygalae and Rhizoma Acori Graminei have been used for disease in relation to brain retrogression. We studied of anti-Alzheimer effect on CT105-induced neuroblastoma cell lines by Radix Polygalae(RP) and Rhizoma Acori Graminei(RAG) water extract. As the result of this study, In RP and RAG group, the apoptosis in the nervous system is inhibited, the repair against the degeneration of Neuroblastoma cells by CT105 expression is induced. These results indicate that In RP and RAG, RAG possess the strongest in inhibitory effect of apoptosis in the nervous system and repair effect against the degeneration of Neuroblastoma cells by CT105 expression.

• Molecular & Cellular Toxicology
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• v.4 no.2
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• pp.157-163
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• 2008

Formation of ${\beta}$-amyloid $(A{\beta})$ fibrils has been identified as one of the major characteristics of Alzheimer's disease (AD). Inhibition of $A{\beta}$ fibril formation in the CNS would be attractive therapeutic targets for the treatment of AD. Several small compounds that inhibit amyloid formation or amyloid neurotoxicity in vitro have been known. Citrate has surfactant function effect because of its molecular structure having high anionic charge density, in addition to the well-known antibacterial and antioxidant properties. Therefore, we hypothesized that citrate might have the inhibitory effect against $A{\beta}$ fibril formation in vitro and have the protective effect against $A{\beta}$-induced neurotoxicity in PC12 cells. We examined the effect of citrate against the formation of $A{\beta}$ fibrils by measuring the intensity of fluorescence in thioflavin-T (Th-T) assay of between $A{\beta}_{25-35}$ groups treated with citrate and the control with $A{\beta}_{25-35}$ alone. The neuroprotective effect of citrate against $A{\beta}$-induced toxicity in PC12 cells was investigated using the WST-1 assay. Fluorescence spectroscopy showed that citrate inhibited dose-dependently the formation of $A{\beta}$ fibrils from ${\beta}$-amyloid peptides. The inhibition percentages of $A{\beta}$ fibril formation by citrate (1, 2.5, and 5 mM) were 31%, 60%, and 68% at 7 days, respectively in thioflavin-T (Th-T) assay. WST-1 assay revealed that the toxic effect of $A{\beta}_{25-35}$ was reduced, in a dose-dependent manner to citrate. The percentages of neuroprotection by citrate (1, 2.5, and 5 mM) against $A{\beta}-induced$ toxicity were 19%, 31 %, and 34%, respectively. We report that citrate inhibits the formation of $A{\beta}$ fibrils in vitro and has neuroprotective effect against $A{\beta}$-induced toxicity in PC12 cells. Neuroprotective effects of citrate against $A{\beta}$ might be, to some extent, attributable to its inhibition of $A{\beta}$ fibril formation. Although the mechanism of anti-amyloidogenic activity is not clear, the possible mechanism is that citrate might have two effects, salting-in and surfactant effects. These results suggest that citrate could be of potential therapeutic value in Alzheimer's disease.

• Korean Journal of Medicinal Crop Science
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• v.27 no.6
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• pp.365-375
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• 2019

Background: Oxidative stress plays an important role in neuro-degenerative disorders such as Alzheimer's disease. Oxidative stress is mediated by reactive oxygen species (ROS), which are implicated in the pathogenesis of numerous diseases, and account for the toxicity of a wide range of compounds. Methods and Results: In order to study the neuro-protective effect of the complex extracts of Aster scaber Thunberg (AS) and Chaenoleles sinensis Koehne (CSK) against hydrogen peroxide in PC12 cells, cell viability was evaluated by the MTT assay using tetrazole, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and the intracellular ROS levels were determined the by 2',7'-dichlorofluorescein diacetate (DCF-DA) assay. In order to examine the anti-amnesic effects of the complex extracts of AS and CSK, behavioral tests were performed on male ICR mice. The ameliorating effect of the complex extracts against Aβ_1-42-induced learning and memory impairment was analyzed by y-maze and passive avoidance tests. The AS and CSK extracts showed neuro-protective activity both in vitro and in vivo, and the neuro-protective effect of their 60 : 40 (AS : CSK) mixture was better than that of the other mixtures. Moreover, the complex extracts synergistically inhibited acetylcholinesterase activity and rapid peroxidation. Conclusions: A mixture of the AS and CSK extracts could be used to develop functional foods and serve as raw materials for the development of therapeutics against Alzheimer's disease.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.954-960
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• 2004

Expression of the NF-$textsc{k}$B-dependent genes responsible for inflammation, such as TNF-$\alpha$, IL-1$\beta$, and nitric oxide synthase (NOS), contributes to chronic inflammation which is a major cause of neurodegenerative diseases (i.e. Alzheimer＇s disease). Although NF-$textsc{k}$B plays a biphasic role in different cells like neurons and microglia, controlling the activation of NF-$textsc{k}$B is important for its negative feedback in either activation or inactivation. In this study, we found that ursodeoxycholic acid (UDCA) inhibited I$textsc{k}$B$\alpha$ degradation to block expression of the NF-$textsc{k}$B-dependent genes in microglia when activated by $\beta$-amyloid peptide (A$\beta$). We also showed that when microglia is activated by $A\beta$42, the expression of A20 is suppressed. These findings place A20 in the category of ' protective ' genes, protecting cells from pro-inflammatory reper-toires induced in response to inflammatory stimuli in activated microglia via NF-$textsc{k}$B activation. In light of the gene and proteins for NF-$textsc{k}$B-dependent gene and inactivator for NF-$textsc{k}$B (I$textsc{k}$B$\alpha$), the observations now reported suggest that UDCA plays a role in supporting the attenuation of the production of pro-inflammatory cytokines and NO via inactivation of NF-$textsc{k}$B. Moreover, an NF-$textsc{k}$B inhibitor such as A20 can collaborate and at least enhance the anti-inflammatory effect in microglia, thus giving a potent benefit for the treatment of neurodegenerative diseases such as AD.uch as AD.

• Nutrition Research and Practice
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• v.10 no.3
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• pp.274-281
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• 2016

BACKGROUND/OBJECTIVES: The accumulation of amyloid-${\beta}$ ($A{\beta}$) in the brain is a hallmark of Alzheimer's disease (AD) and plays a key role in cognitive dysfunction. Perilla frutescens var. japonica extract (PFE) and its major compound, rosmarinic acid (RA), have shown antioxidant and anti-inflammatory activities. We investigated whether administration of PFE and RA contributes to cognitive improvement in an $A{\beta}_{25-35}$-injected mouse model. MATERIALS/METHODS: Male ICR mice were intracerebroventricularly injected with aggregated $A{\beta}_{25-35}$ to induce AD. $A{\beta}_{25-35}$-injected mice were fed PFE (50 mg/kg/day) or RA (0.25 mg/kg/day) for 14 days and examined for learning and memory ability through the T-maze, object recognition, and Morris water maze test. RESULTS: Our present study demonstrated that PFE and RA administration significantly enhanced cognition function and object discrimination, which were impaired by $A{\beta}_{25-35}$, in the T-maze and object recognition tests, respectively. In addition, oral administration of PFE and RA decreased the time to reach the platform and increased the number of crossings over the removed platform when compared with the $A{\beta}_{25-35}$-induced control group in the Morris water maze test. Furthermore, PFE and RA significantly decreased the levels of nitric oxide (NO) and malondialdehyde (MDA) in the brain, kidney, and liver. In particular, PFE markedly attenuated oxidative stress by inhibiting production of NO and MDA in the $A{\beta}_{25-35}$-injected mouse brain. CONCLUSIONS: These results suggest that PFE and its active compound RA have beneficial effects on cognitive improvement and may help prevent AD induced by $A{\beta}$.

• The Journal of Natural Sciences
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• v.19 no.1
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• pp.45-55
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• 2008

Alzheimer's disease is charaterized by the acetylcholine depletion, amyloid b-protein aggregation and neurofibrillary tangles. The prevention of the breakdown of acetylcholine by acetylcholinesterase (AChE) inhibitor has the best clinically therapeutic efficacy for Alzheimer's disease patients. To develop new antidementia alternative drugs or nutraceuticals, methanol extracts of Sorghum bicolor was screened from various extracts of cereals and legumes as a potent AChE inhibitor-containing extract in previous paper. In this paper, physicochemical properties of the methanol extracts was investigated. The methanol extracts was soluble by water, methanol and DMSO and had 215 nm and 282nm of maximum absorption spectra. It was also stable at 20-$100^{\circ}C$ and pH 2.0-10.0 for 1 hr. Test product was prepared by using methanol extracts from Sorghum bicolor and changes of its quality during storge at $20^{\circ}C$ and $40^{\circ}C$ were investigated. It was very stable for 8 weeks at $40^{\circ}C$.

• Korean Journal of Medicinal Crop Science
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• v.16 no.6
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• pp.409-415
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• 2008

Moutan cortex, the root bark of Paeonia suffruticosa Andrews (Paeoniaceae), has pharmacological effects such as anti-inflammatory, antiallergic, analgesic and antioxidant activities. We investigated a methanol extract of Moutan cortex for neuroprotective effects on neurotoxicity induced by amyloid ${\beta}$ protein ($A{\beta}$) (25-35) in cultured rat cortical neurons. Exposure of cultured cortical neurons to $10\;{\mu}M\;A{\beta}$ (25-35) for 24 h induced neuronal apoptotic death. Moutan cortex inhibited $10\;{\mu}M\;A{\beta}$ (25-35)-induced neuronal cell death at 30 and $50\;{\mu}g/m{\ell}$, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. Moutan cortex inhibited $10\;{\mu}M\;A{\beta}$ (25-35)-induced elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), and generation of reactive oxygen species (ROS) which were measured by fluorescent dyes. Moutan cortex also inhibited glutamate release into medium induced by $10\;{\mu}M\;A{\beta}$ (25-35), which was measured by HPLC. These results suggest that Moutan cortex prevents $A{\beta}$ (25-35)-induced neuronal cell damage by interfering with the increase of $[Ca^{2+}]_i$, and then inhibiting glutamate release and ROS generation. Moutan cortex may have a therapeutic role in preventing the progression of Alzheimer's disease.

• Journal of Chitin and Chitosan
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• v.23 no.4
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• pp.220-227
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• 2018

Amyloid plaque is a product of aggregation of ${\beta}$-amyloid peptide ($A{\beta}$) and is an important factor in the pathogenesis of Alzheimer's Disease (AD). $A{\beta}$ is a major component of amyloid plaque and vascular deposits in the AD brain. The enzyme ${\beta}$-secretase is required for the production of $A{\beta}$; thus, prevention of the formation of $A{\beta}$ through the inhibition of ${\beta}$-secretase is a major focus in the study of the treatment of AD. In this study, we investigated ${\beta}$-secretase inhibitory activity of an Arctoscopus japonicus peptide. An Alcalase hydrolysate had the highest ${\beta}$-secretase inhibitory activity. A ${\beta}$-secretase inhibitory activity peptide was separated using ion exchange column chromatography (carboxy-methyl: CM, quaternary methyl ammonium: QMA) and reverse phase high performance liquid chromatography (RP-HPLC) on a C18 column. The $IC_{50}$ value of the purified peptide was $248.2{\pm}1.73{\mu}g/mL$. The ${\beta}$-secretase inhibitory peptide was identified as a six amino acid residue of Gly-Pro-Val-Gly-Ala-Pro (MW: 497.27 Da). In cell viability experiments, the final purified fraction, the carboxy-methyl ion exchange column fraction (CM-F1) showed no significant cytotoxic effect in SH-SY5Y cells at concentrations below $100{\mu}g/mL$ in 24 h. The results of this study suggest that peptides separated from Arctoscopus japonicus may be beneficial as ${\beta}$-secretase inhibitor compounds in functional foods.