• YAKHAK HOEJI
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• v.51 no.4
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• pp.264-269
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• 2007

Alzheimer’s disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}-amyloid $ (A ${\beta}$) peptides, which are generated by processing of amyloid precursor protein (APP). It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. A${\beta}$ peptides have been believed to be neurotoxic and now are also considered to have effects on the mechanism of memory formation. In this study, effects of radicicol on the metabolism of APP were analyzed. Radicicol inhibited the secretion of A${\beta}$ from the Neuro2a cell line (APPswe cell) expressing APPswe. Beta-site APP cleaving enzyme (BACE) fluorescence resonance energy transfer (FRET) assay revealed that it inhibited BACE activity in a dose dependently manner. Immunoblotting study showed that it inhibited intracellular heat shock protein (HSP)90 and it increased the secretion of HSP90 from the APPswe cells. We suggest that radicicol inhibits APP metabolism and Ap generation by the means of HSP90 inhibitory mechanism and partially BACE inhibitory mechanism. This is the first report that radicicol inhibits the secretion of A${\beta}$ peptides from neuroblastoma cells.

• Korean Journal of Medicinal Crop Science
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• v.13 no.5
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• pp.219-226
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• 2005

Sanguisorbae radix (SR) from Sanguisorba officinalis L. (Losaceae) is widely used in Korea and China due to its various pharmacological activity. The present study aims to investigate the effect of the methanol extract of SR on amyloid ${\beta}$ Protein(25-35) $(A{\beta}\;(25-35))$, a synthetic 25-35 amyloid peptide, -induced neurotoxicity using cultured rat cortical neurons. SR, over a concentration range of $10-50\;{\mu}g/ml$, inhibited the $A{\beta}$ (25-35) $(10\;{\mu}M)-induced$ neuronal cell death, as assessed by a 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. Pretreatment of SR $(50\;{\mu}g/ml)$ inhibited $10\;{\mu}M\;A{\beta}$ (25-35)-induced} elevation of cytosolic calcium concentration $([Ca^{2+}]c)$, which was measured by a fluorescent dye, fluo-4 AM. SR $(10\;and\;50\;{\mu}g/ml)$ inhibited glutamate release into medium induced by $10\;{\mu}M\;A{\beta}(25-35)$, which was measured by HPLC, and generation of reactive oxygen species. These results suggest that SR prevents $A{\beta}$ (25-35)-induced neuronal cell damage in vitro.

• The Journal of Internal Korean Medicine
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• v.21 no.2
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• pp.235-241
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• 2000

호도(胡桃)(Juglandis semen)가 치매에 미치는 영향을 알아보기 위하여 치매(Alzheimer's disease) 유발물질로 알려진 amyloid-{$\beta}(A{\beta})$ 25-35를 흰쥐의 뇌 신경세포의 일종인 astrocyte에 처리한 후 뇌의 신경세포에 대한 독성 및 세포막에서의 지질 과산화에 미치는 영향을 검토하였다. 호도(胡桃)는 $A{\beta})$ 25-35로 인한 신경세포의 파괴를 억제하는 것으로 나타나 신경세포의 손상을 예방하고 보호하는 효과가 있었다. 그리고, 지질의 과산화 지표인 malondialdehyde 생성은 $A{\beta})$ 25-35 처리로 크게 증가하였으나, 호도(胡桃)의 전처리와 후처리로 크게 감소되어 호도(胡桃)가 세포막 파괴로 인한 뇌세포의 손상을 방지하는 것으로 나타났다. 이러한 결과들을 볼 때, 호도(胡桃)는 신경세포의 하나인 astrocyte에 대한 보호효과와 세포막에서 지질의 과산화를 저해 및 $A{\beta})$ 25-35 처리와 같은 치매 유발 독성에 대한 적응능력 향상을 통하여 뇌 신경세포를 보호하는 효과가 있음을 보여주는 것으로 노인성 치매 등의 임상적 응용에 그 효과가 기대된다.

• Natural Product Sciences
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• v.21 no.2
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• pp.134-140
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• 2015

The present study aims to investigate the effect of methanol extract of Korean mistletoe (KM; Viscum album var. coloratum), on amyloid $\beta$ protein ($A\beta$) (25-35), a synthetic 25-35 amyloid peptide, -induced neurotoxicity in cultured rat cerebral cortical neurons and memory impairment in mice. Exposure of cultured neurons to $10{\mu}M$ $A\beta$ (25-35) for 24 h induced a neuronal cell death, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. KM (10, 30 and $50{\mu}g/ml$) significantly inhibited the $A\beta$ (25-35)-induced apoptotic neuronal death. KM ($50{\mu}g/ml$) inhibited 10 μM Aβ (25-35)-induced elevation of intracellular calcium concentration ([Ca²⁺]_i), which was measured by a fluorescent dye, Fluo-4 AM. Glutamate release into medium and generation of reactive oxygen species (ROS) induced by $10{\mu}M$ $A\beta$ (25-35) were also inhibited by KM (10, 30 and $50{\mu}g/ml$). These results suggest that KM may mitigate the $A\beta$ (25-35)-induced neurotoxicity by interfering with the increase of [Ca²⁺]_i and then inhibiting glutamate release and generation of ROS in cultured neurons. In addition, orally administered KM (25 and 50 mg/kg, 7 days) significantly prevented memory impairment induced by intracerebroventricular injection of $A\beta$ (25-35) (8 nmol). Taken together, it is suggested that anti-dementia effect of KM is due to its neuroprotective effect against $A\beta$ (25-35)-induced neurotoxicity and that KM may have therapeutic role in prevention of the progression of Alzheimer's disease.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.145-151
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• 2020

Alzheimer's disease (AD) is a devastating neurodegenerative disease and a major cause of dementia in elderly individuals worldwide. Increased deposition of insoluble amyloid β (Aβ) fibrils in the brain is thought be a key neuropathological hallmark of AD. Many recent studies show that natural products such as polyphenolic flavonoids inhibit the formation of insoluble Aβ fibrils and/or destabilize β-sheet-rich Aβ fibrils to form non-cytotoxic aggregates. In the present study, we explored the structure-activity relationship of naturally-occurring biflavonoids on Aβ amyloidogenesis utilizing an in vitro thioflavin T assay with Aβ1-42 peptide which is prone to aggregate more rapidly to fibrils than Aβ1-40 peptide. Among the biflavonoids we tested, we found amentoflavone revealed the most potent effects on inhibiting Aβ1-42 fibrillization (IC₅₀: 0.26 µM), as well as on disassembling preformed Aβ1-42 fibrils (EC₅₀: 0.59 µM). Our structure-activity relationship study suggests that the hydroxyl groups of biflavonoid compounds play an essential role in their molecular interaction with the dynamic process of Aβ1-42 fibrillization. Our atomic force microscopic imaging analysis demonstrates that amentoflavone directly disrupts the fibrillar structure of preformed Aβ1-42 fibrils, resulting in conversion of those fibrils to amorphous Aβ1-42 aggregates. These results indicate that amentoflavone affords the most potent anti-amyloidogenic effects on both inhibition of Aβ1-42 fibrillization and disaggregation of preformed mature Aβ1-42 fibrils.

• Biomolecules & Therapeutics
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• v.15 no.1
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• pp.34-39
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• 2007

Alzheimer's disease (AD) is an abnormal accumulation of the ${\beta}$-amyloid protein $(A{\beta})$ in specific brain region. It has been speculated that disturbance in cholesterol homeostasis may contribute to the etiology of AD by increasing $A{\beta}$ generation. However, conclusive evidence and possible mechanism has not been reported. In the present study, we demonstrated that rabbits treated with 0.5% cholesterol for 16 weeks increased serum total cholesterol, triacylglycerol, and low-density lipoprotein levels. $A{\beta}$ levels is higher in the hippocampus of brain in cholesterol dieted rabbits than that of normal diet rabbis. Expression and activities of ${\beta}-$ and ${\gamma}-$ secretases, the enzymes that cleave ${\beta}$-amyloid precursor protein to generate $A{\beta}$, were also increased in hippocampus of high cholesterol dieted rabbit than those of normal dieted rabbits. Our results suggest that high cholesterol diet may be associated with increased $A{\beta}$ accumulation in the brain of rabbits, and suggest that high cholesterol diet may be causal factor in the development or progression of AD.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.6
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• pp.689-696
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• 2018

Increasing evidence implicates changes in $[Ca^{2+}]_i$ and oxidative stress as causative factors in amyloid beta ($A{\beta}$)-induced neuronal cell death. Cyanidin-3-glucoside (C3G), a component of anthocyanin, has been reported to protect against glutamate-induced neuronal cell death by inhibiting $Ca^{2+}$ and $Zn^{2+}$ signaling. The present study aimed to determine whether C3G exerts a protective effect against $A{\beta}_{25-35}$-induced neuronal cell death in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague-Dawley rats using MTT assay for cell survival, and caspase-3 assay and digital imaging methods for $Ca^{2+}$, $Zn^{2+}$, MMP and ROS. Treatment with $A{\beta}_{25-35}$ ($20{\mu}M$) for 48 h induced neuronal cell death in cultured rat pure hippocampal neurons. Treatment with C3G for 48 h significantly increased cell survival. Pretreatment with C3G for 30 min significantly inhibited $A{\beta}_{25-35}$-induced $[Zn^{2+}]_i$ increases as well as $[Ca^{2+}]_i$ increases in the cultured rat hippocampal neurons. C3G also significantly inhibited $A{\beta}_{25-35}$-induced mitochondrial depolarization. C3G also blocked the $A{\beta}_{25-35}$-induced formation of ROS. In addition, C3G significantly inhibited the $A{\beta}_{25-35}$-induced activation of caspase-3. These results suggest that cyanidin-3-glucoside protects against amyloid ${\beta}$-induced neuronal cell death by reducing multiple apoptotic signals.

• Journal of Microbiology and Biotechnology
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• v.13 no.5
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• pp.809-814
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• 2003

${\beta}-amyloid$ ($A{\beta}$) peptides from the proteolytic processing of ${\beta}-amyloid$ precursor protein (${\beta}-APP$) aggregates in the brain to form senile plaques, and their aggregation plays a key role in pathogenesis of Alzheimer's disease (AD). To isolate an active compound that has an $A{\beta}$ aggregation-inhibitory activity, 2,000 microbial metabolite libraries were screened based on their ability to inhibit $A{\beta}$ aggregation by using both Congo red and thioflavin T assays. As a result, a water-soluble fraction of a soil microorganism, KK565, showed a potent $A{\beta}$ aggregation-inhibitory activity. The strain was identified as Streptomyces species, based on the cultural and morphological characteristics, the presence of diaminopimelic acid in the cell wall, and the sugar patterns for the whole-cell extract. In addition, the purification of active principle resulted in identifying a heat-unstable protein responsible for the $A{\beta}$ aggregation-inhibitory activity.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.100-107
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• 2013

This study examined the effect of fermented ginseng (FG) on memory impairment and ${\beta}$-amyloid ($A{\beta}$) reduction in models of Alzheimer's disease (AD) in vitro and in vivo. FG extract was prepared by steaming and fermenting ginseng. In vitro assessment measured soluble $A{\beta}42$ levels in HeLa cells, which stably express the Swedish mutant form of amyloid precursor protein. After 8 h incubation with the FG extract, the level of soluble $A{\beta}42$ was reduced. For behavioral assessments, the passive avoidance test was used for the scopolamine-injected ICR mouse model, and the Morris water maze was used for a transgenic (TG) mouse model, which exhibits impaired memory function and increased $A{\beta}42$ level in the brain. FG extract was treated for 2 wk or 4 mo on ICR and TG mice, respectively. FG extract treatment resulted in a significant recovery of memory function in both animal models. Brain soluble $A{\beta}42$ levels measured from the cerebral cortex of TG mice were significantly reduced by the FG extract treatment. These findings suggest that FG extract can protect the brain from increased levels of $A{\beta}42$ protein, which results in enhanced behavioral memory function, thus, suggesting that FG extract may be an effective preventive or treatment for AD.

• Journal of Acupuncture Research
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• v.20 no.4
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• pp.145-156
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• 2003

Objective : This study is to investigate the effect of electro-acupuncture ST36 on altered transmission of afferent somatosensory information caused by amyloid-${\beta}$(A-${\beta}$) that caused Alzheimer's disease. Methods : The effects of topical application of A-${\beta}$, A-${\beta}$ with ST36, aggregated A-${\beta}$(aA-${\beta}$), aA-${\beta}$ with ST36 and ST36 on the afferent sensory transmission to the neurons in the primary somatosensory(SI) cortex was observed in anesthetized rats. Quantitative determination of the effects of A-${\beta}$, A-${\beta}$ with ST36, aA-${\beta}$, aA-${\beta}$ with ST36 and ST36 was made by generating poststimulus time histogram of evoked response of individual cortical neuron by electrical stimulation of the receptive located in peripheral area(forepaw) Results : The results obtained in present study were summerized as follow : 1. Application of physiological concentrative 0.5 nM A-${\beta}$ caused afferent sensory transmission of SI cortex facilitated. 0.5 nM A-${\beta}$ with ST36 exerted much stronger effects than 0.5 nM A-${\beta}$ alone. 2. Application of $10{\mu}M$ A-${\beta}$ caused afferent sensory transmission of SI cortex unchangeable. But $10{\mu}M$ A-${\beta}$ with ST36 is facilitated at 30 min of post-drug period 3. Application of $10{\mu}M$ aA-${\beta}$ caused afferent sensory transmission of SI cortex diminished. $10{\mu}M$ aA-${\beta}$ with ST36 is diminished after 15min of post-drug period but is facilitated after 75min.