• Molecules and Cells
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• 제42권1호
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• pp.36-44
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• 2019

Alzheimer's disease (AD) is the most frequent age-related human neurological disorder. The characteristics of AD include senile plaques, neurofibrillary tangles, and loss of synapses and neurons in the brain. ${\beta}-Amyloid$ ($A{\beta}$) peptide is the predominant proteinaceous component of senile plaques. The amyloid hypothesis states that $A{\beta}$ initiates the cascade of events that result in AD. Amyloid precursor protein (APP) processing plays an important role in $A{\beta}$ production, which initiates synaptic and neuronal damage. ${\delta}-Catenin$ is known to be bound to presenilin-1 (PS-1), which is the main component of the ${\gamma}-secretase$ complex that regulates APP cleavage. Because PS-1 interacts with both APP and ${\delta}-catenin$, it is worth studying their interactive mechanism and/or effects on each other. Our immunoprecipitation data showed that there was no physical association between ${\delta}-catenin$ and APP. However, we observed that ${\delta}-catenin$ could reduce the binding between PS-1 and APP, thus decreasing the PS-1 mediated APP processing activity. Furthermore, ${\delta}-catenin$ reduced PS-1-mediated stabilization of APP. The results suggest that ${\delta}-catenin$ can influence the APP processing and its level by interacting with PS-1, which may eventually play a protective role in the degeneration of an Alzheimer's disease patient.

• 한국수산과학회지
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• 제53권6호
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• pp.886-893
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• 2020

The seaweed Hizikia fusiformis is rich in protein, carbohydrates, vitamins, and minerals. This study investigated the antioxidant and physiological activities of H. fusiformis extracts prepared with 70% ethanol, 80% methanol, or distilled water. The extraction yields of these various solvent extracts were as follows: ethanol extract, 15.26%; methanol extract, 17.95%; and water extract, 45.62%. The methanol extract showed the highest total polyphenol content (24.06 mg GAE/g), but total flavonoid content was similar in all extracts. ABTS (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radical scavenging activity was highest in the ethanol extract (IC50: 0.90 mg/mL), while the methanol extract exhibited the strongest DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity (IC50: 8.09 mg/mL), reducing power (EC50: 0.40 mg/mL), and ferric reducing antioxidant power (0.28 mM). By contrast, tyrosinase and α-glucosidase inhibitory activities were higher in the ethanol extract than in the other extracts. The high BACE1 (β-secretase) inhibitory activity was observed in the ethanol extract (IC50: 1.03 mg/mL). These results indicate that H. fusiformis ethanol extracts may be useful for their antioxidant and functional properties in food and pharmaceutical materials.

• 한국수산과학회지
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• 제55권3호
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• pp.310-318
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• 2022

Cnidium japonicum a biennial plant belonging to the family Umbelliferae, is a halophyte that grows in high-salinity areas of coastal sand dunes and sandy shores. This study was conducted to investigate the constituents, antioxidant activities, and physiological activities of C. japonicum. Mineral analyses revealed that potassium, sodium, calcium, and magnesium were the most prevalent minerals in C. japonicum. We used 80% ethanol, 80% methanol, and distilled water as solvents to prepare extracts from C. japonicum tissues, and the obtained extraction yields ranged between approximately 26% and 32%. Among the three extracts, the ethanol and methanol extracts had higher total polyphenol and flavonoid levels than the water extracts did. The antioxidant activities of methanol extracts were the highest among the various solvent extracts of C. japonicum as was the elastase/collagenase inhibitory activity. In contrast, the ethanol extract exhibited the highest tyrosinase inhibitory activity. Furthermore, the methanol extract possessed over 80% BACE1 (β-secretase) inhibitory activity at a final concentration of 20 ㎍/mL. Therefore, these results indicate that methanol and ethanol extracts of C. japonicum may be useful as antioxidant and functional substances in food and pharmaceutical material.

• 한국수산과학회지
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• 제54권6호
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• pp.938-947
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• 2021

Messerschmidia sibirica is a halophyte that grows in high-salinity areas of coastal sand dunes and sandy shores. This study was conducted to investigate the constituents, antioxidant potency, and physiological activities of M. sibirica. Mineral analyses revealed that potassium, calcium, sodium, and magnesium were the most prevalent minerals in M. sibirica leaves and stems. We used 70% ethanol, 80% methanol, and distilled water as solvents to prepare extracts from M. sibirica tissues, with extraction yields of between approximately 19% and 27% being obtained. Among the six types of extract, the leaf ethanol extract (LEE) was characterized by the highest total polyphenol and flavonoid contents, and the antioxidant activities of the LEE were also the highest among the different solvent extracts. In addition, the leaf water extract was shown to have the highest tyrosinase and α-glucosidase inhibitory activities, whereas the leaf methanol extract was found to have the highest elastase inhibitory activity. Notably, all leaf extracts were established to have more than 75% β-secretase (BACE1) inhibitory activity at a final concentration of 0.5 mg/mL. These results indicate that leaf extracts of M. sibirica may have beneficial antioxidant properties, and could thus have potential application as functional supplements in food and pharmaceutical products.

• 한국수산과학회지
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• 제55권6호
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• pp.858-866
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• 2022

The present study investigated the chemical composition, and antioxidant and physiological activities of the Korean marine algae, Codium fragile. The solvent extracts from C. fragile were prepared using 70% ethanol, 80% methanol, and distilled water. Based on the general chemical composition, carbohydrate, crude protein, crude lipid, crude ash, and moisture were 74.22%, 16.73%, 0.66%, 4.39%, and 4.00%, respectively. Calcium, magnesium, sodium and potassium were the main minerals. The extraction yield range of the solvent extracts was 3.51-9.76%. The ranges of total polyphenol and flavonoid contents were approximately 10.97-13.76 mg/g and 8.00-8.69 mg/g, respectively. The ABTS [2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)] radical scavenging activity, reducing power and FRAP (ferric reducing antioxidant power) activities were the highest in the ethanol extract, while methanol extract exhibited the strongest nitrite oxide scavenging activity. On the other hand, tyrosinase, elastase, and xanthine oxidase inhibitory activities of the ethanol and methanol extracts were higher than those of the water extract. Furthermore, the ethanol extract exhibited the highest β-secretase inhibitory activity. The results indicate that C. fragile can be used as an antioxidant and a functional ingredient in food and pharmaceutical products.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2021년도 춘계학술대회
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• pp.58-58
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• 2021

Although hypoxic/ischemic injury is thought to contribute to the incidence of Alzheimer disease (AD), the molecular mechanism that determines the relationship between hypoxia-induced β-amyloid (Aβ) generation and development of AD is not yet known. In this study, we investigated the protective effects of Acorus gramineus Soland. (AGS) on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced A β production in SH-SY5Y human neuroblastoma cells. Pretreatment of these cells with AGS significantly attenuated OGD/R-induced production of reactive oxygen species (ROS) and elevation of levels of malondialdehyde, nitrite (NO), prostaglandin E2 (PGE2), cytokines (TNF-α, IL-1β and IL-6) and glutathione, as well as superoxide dismutase activity. AGS also reduced OGD/R-induced expression of the apoptotic protein caspase-3, the apoptosis regulator Bcl-2, and the autophagy protein becn-1. Finally, AGS reduced OGD/R-induced Aβ production and cleavage of amyloid precursor protein, by inhibiting secretase activity and suppressing the autophagic pathway. Although supporting data from in vivo studies are required, our results indicate that AGS may prevent neuronal cell damage from OGD/R-induced toxicity.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.165-170
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• 2023

Isolation of the culture broth of a marine-derived Acremonium sp. CNQ-049 guided by HPLC-UV yielded compound 1 (3-phenethyl-2-phenylquinazolin-4(3H)-one), and its inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-secretase 1 (BACE1) were evaluated. Compound 1 was an effective selective MAO-B inhibitor with an IC₅₀ value of 9.39 µM and a selectivity index (SI) value of 4.26 versus MAO-A. In addition, compound 1 showed a potent selective butyrylcholinesterase (BChE) inhibition with an IC₅₀ value of 7.99 µM and an SI value of 5.01 versus acetylcholinesterase (AChE). However, compound 1 showed weak inhibitions against MAO-A, AChE, and BACE1. The Ki value of compound 1 for MAO-B was 5.22±1.73 µM with competitive inhibition, and the Ki value of compound 1 for BChE was 3.00±1.81 µM with mixed-type inhibition. Inhibitions of MAO-B and BChE by compound 1 were recovered by dialysis experiments. These results suggest that compound 1 is a dual-functional reversible inhibitor of MAO-B and BChE, that can be used as a treatment agent for neurological disorders.

• Journal of Web Engineering
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• 제13권12호
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• pp.4370-4388
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• 2021

Amyloid-β (Aβ) accumulation in the hippocampus is an essential event in the pathogenesis of Alzheimer's disease. Insoluble Aβ is formed through the sequential proteolytic hydrolysis of the Aβ precursor protein, which is cleaved by proteolytic secretases. However, the pathophysiological mechanisms of Aβ accumulation remain elusive. Here, we report that rats fed high-phytate diets showed Aβ accumulation and increased apoptotic neuronal cell death in the hippocampus through the activation of the amyloidogenic pathway in the hippocampus. Immunoblotting and immunohistochemical analyses confirmed that the overexpression of BACE1 β-secretase, a critical enzyme for Aβ generation, exacerbated the hippocampal Aβ accumulation in rats fed high-phytate diets. Moreover, we identified that parathyroid hormone, a physiological hormone responding to the phytate-mediated dysregulation of calcium and phosphate homeostasis, plays an essential role in the transcriptional activation of the Aβ precursor protein and BACE1 through the vitamin D receptor and retinoid X receptor axis. Thus, our findings suggest that phytate-mediated dysregulation of calcium and phosphate is a substantial risk factor for elevated Aβ accumulation and apoptotic neuronal cell death in rats.

• 대한본초학회지
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• 제29권6호
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• pp.73-83
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• 2014

Objectives : This study was investigated the effects of the root of Polygala tenuifolia (POL) on learning and memory impairment induced by chronic cerebral hypoperfusion in rats. Methods : Chronic cerebral hypoperfusion was produced by permanent bilateral common carotid artery occlusion (pBCAO). POL was administered orally once a day (130 mg/kg of water-extract) for 28 days starting at 4 weeks after the pBCAO. The acquisition of learning and the retention of memory were tested on 9th week after the pBCAO using the Morris water maze. In addition, effects of POL on $A{\beta}$ generation and expressions of APP and BACE1 were observed in the hippocampus of rats. Results : POL significantly prolonged the swimming time spent in target quadrant and significantly reduced the swimming time spent in the quadrant far from the target. POL significantly increased the percentage of swim in the targer quadrant in the retention test, while POL was not effective on the escape latencies in the acquisition training trials. POL significantly reduced the levels of $A{\beta}_{(1-40)}$ and $A{\beta}_{(1-42)}$ in the cerebral cortex and the level of $A{\beta}_{(1-42)}$ in the hippocampus produced by chronic cerebral hypoperfusion. POL also significantly attenuated the up-regulation of APP and BACE1 expression in the hippocampus produced by chronic cerebral hypoperfusion. Conclusions : The results show that POL alleviated memory deficit and up-regulation of $A{\beta}$ and BACE1 expressions in the hippocampus. This result suggests that POL may exert ameliorating effect on memory deficit through inhibition of ${\beta}$-secretase activity and $A{\beta}$ generation.

• 동의신경정신과학회지
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• 제19권2호
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• pp.41-64
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• 2008

Objective: Hominis Placenta is used in many cure, mainly treats a weak, chronic disease, especially senile. This research investigates the effect of the Hominis Placenta Herbal-Acupuncture Solution on Alzheimer's disease. Method: The effects of the Hominis Placenta Herbal-Acupuncture Solution on (1) $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, and CD68/CD11b (2) the behavior (3) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with 13A were investigated. Results: 1. For the Hominis Placenta Herbal-Acupuncture Solution group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}$ A in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 2. The Hominis Placenta Herbal-Acupuncture Solution group suppressed the over-expression of $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, and CD68/CD11b, in the mice with Alzheimer's disease induced by ${\beta}A$. 3. The Hominis Placenta Herbal Acupuncture Solution group reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. 4. The Hominis Placenta Herbal-Acupuncture Solution group reduced the Tau protein, GFAP protein, and presenilin1/2 protein, beta-secretase protein, (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by ${\beta}A$. Conclusion: These results suggest that the Hominis Placenta Herbal-Acupuncture Solution group may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the Hominis Placenta Herbal-Acupuncture Solution for Alzheimer's disease is suggested for future research.