• Journal of Ginseng Research
• /
• v.41 no.4
• /
• pp.566-571
• /
• 2017

Background: A number of reports have described the protective effects of ginsenoside Rg1 (Rg1) in Alzheimer's disease (AD). However, the protective mechanisms of Rg1 in AD remain elusive. Methods: To investigate the potential mechanisms of Rg1 in ${\beta}$-amyloid peptide-treated SH-SY5Y cells, a comparative proteomic analysis was performed using stable isotope labeling with amino acids in cell culture combined with nano-LC-MS/MS. Results: We identified a total of 1,149 proteins in three independent experiments. Forty-nine proteins were significantly altered by Rg1 after exposure of the cells to ${\beta}$-amyloid peptides. The protein interaction network analysis showed that these altered proteins were clustered in ribosomal proteins, mitochondria, the actin cytoskeleton, and splicing proteins. Among these proteins, mitochondrial proteins containing HSD17B10, AARS2, TOMM40, VDAC1, COX5A, and NDUFA4 were associated with mitochondrial dysfunction in the pathogenesis of AD. Conclusion: Our results suggest that mitochondrial proteins may be related to the protective mechanisms of Rg1 in AD.

• Journal of Integrative Natural Science
• /
• v.6 no.3
• /
• pp.143-150
• /
• 2013

Prevailing role of intracellular amyloid ${\beta}$ ($iA{\beta}$) in Alzheimer's disease (AD) initiation and progression attracts more and more attention in recent years. To address whether $iA{\beta}$ induces early alterations of electrophysiological properties in cultured human primary neurons, we delivered $iA{\beta}$ with adenovirus and measured the electrophysiological properties of infected neurons with whole-cell recordings. Our results show that $iA{\beta}$ induces an increase in neuronal resting membrane potentials, a decrease in $K^+$ currents and a hyperpolarizing shift in voltage-dependent activation of $K^+$ currents. These results suggest the electrophysiological impairments induced by $iA{\beta}$ may be responsible for its neuronal toxicity.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.6
• /
• pp.689-696
• /
• 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 Ginseng Research
• /
• v.37 no.1
• /
• pp.100-107
• /
• 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.

• Proceeding of EDISON Challenge
• /
• 2015.03a
• /
• pp.14-23
• /
• 2015

Alzheimer's disease is one of the most common types of degenerative dementia. As a considerable cause of Alzheimer's disease, neurotoxic plaques composed of 39 to 42 residue-long amyloid beta($A{\beta}$) fibrils have been found in the patient's brain in large quantity. A previous study found that erythrosine B (ER), a red color food dye approved by FDA, inhibits the formation of amyloid beta fibril structures. Here, in an attempt to elucidate the inhibition mechanism, we performed molecular dynamics simulations to demonstrate the conformational change of $A{\beta}40$ induced by 2 ERs in atomistic detail. During the simulation, the ERs bound to the surfaces of both N-terminus and C-terminus regions of $A{\beta}40$ rapidly. The observed stacking of the ERs and the aromatic side chains near the N-terminus region suggests a possible inhibition mechanism in which disturbing the inter-chain stacking of PHEs destabilizes beta-sheet enriched in amyloid beta fibrils. The bound ERs block water molecules and thereby help stabilizing alpha helical structure at the main chain of C-terminus and interrupt the formation of the salt-bridge ASP23-LYS28 at the same time. Our findings can help better understanding of the current and upcoming treatment studies for Alzheimer's disease by suggesting inhibition mechanism of ER on the conformational transition of $A{\beta}40$ at the molecular level.

• Journal of Ginseng Research
• /
• v.40 no.3
• /
• pp.278-284
• /
• 2016

Background: The ginsenoside Rb1 (Rb1) is the most abundant compound in the root of Panax ginseng. Recent studies have shown that Rb1 has a neuroprotective effect. However, the mechanisms underlying this effect are still unknown. Methods: We used stable isotope labeling with amino acids in cell culture, combined with quantitative mass spectrometry, to explore a potential protective mechanism of Rb1 in ${\beta}$-amyloid-treated neuronal cells. Results: A total of 1,231 proteins were commonly identified from three replicate experiments. Among these, 40 proteins were significantly changed in response to Rb1 pretreatment in ${\beta}$-amyloid-treated neuronal cells. Analysis of the functional enrichments and protein interactions of altered proteins revealed that actin cytoskeleton proteins might be linked to the regulatory mechanisms of Rb1. The CAP1, CAPZB, TOMM40, and DSTN proteins showed potential as molecular target proteins for the functional contribution of Rb1 in Alzheimer's disease (AD). Conclusion: Our proteomic data may provide new insights into the protective mechanisms of Rb1 in AD.

• BMB Reports
• /
• v.52 no.7
• /
• pp.439-444
• /
• 2019

Although hypoxic/ischemic injury is thought to contribute to the incidence of Alzheimer's disease (AD), the molecular mechanism that determines the relationship between hypoxia-induced ${\beta}$-amyloid ($A{\beta}$) generation and development of AD is not yet known. We have now investigated the protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride (KHG26702), a novel thiazole derivative, on oxygen-glucose deprivation (OGD)-reoxygenation (OGD-R)-induced $A{\beta}$ production in SH-SY5Y human neuroblastoma cells. Pretreatment of these cells with KHG26702 significantly attenuated OGD-R-induced production of reactive oxygen species and elevation of levels of malondialdehyde, prostaglandin $E_2$, interleukin 6 and glutathione, as well as superoxide dismutase activity. KHG26702 also reduced OGD-R-induced expression of the apoptotic protein caspase-3, the apoptosis regulator Bcl-2, and the autophagy protein becn-1. Finally, KHG26702 reduced OGD-R-induced $A{\beta}$ 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 KHG26702 may prevent neuronal cell damage from OGD-R-induced toxicity.

• Korean Journal of Pharmacognosy
• /
• v.53 no.2
• /
• pp.102-110
• /
• 2022

Alzheimer's disease (AD) is the most common form of dementia, and the accumulation of β-amyloid (Aβ) in the brain triggers AD, followed by hyperphosphorylation of tau protein, neurofibrillary tangles, and synapses loss, neuronal cell death, and cognitive decline occur in a chain. In APPswe neuronal cell line, 50 ㎍/ml of Campbell early (Vitis labruscana B.) leaves 50% ethanol extract (VLL) treatment inhibited the secretion of Aβ1-42 by about 63% and the secretion of Aβ1-40 by about 50%. VLL did not target the enzymatic activity of the amyloidogenic pathway and decreased the protein expression of APP. As a result of RT-qPCR (Reverse transcription-quantitative real-time PCR) of the APPswe cell line treated with VLL, it is thought that the protein expression of APP was reduced by inhibiting the transcription process of the APP gene. In addition, VLL inhibited acetylcholinesterase (AChE) enzyme activity in vitro by 27.6% and 54.7%, respectively, at 50 and 100 ㎍/ml concentrations. We found that VLL inhibited the production of Aβ, a dementia-inducing substance, by suppressing the transcription of the APP gene, and that VLL inhibited AChE activity. We suggest that VLL has the potential as a natural drug material that modulates the alleviation of dementia symptoms.

• Journal of the Korean Society of Radiology
• /
• v.84 no.5
• /
• pp.1140-1145
• /
• 2023

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is an encephalopathy caused by inflammation of β-amyloid peptide deposition in cerebrovascular vessels. It is a rare disease that mainly occurs in the elderly and is characterized by rapidly progressive dementia, headache, seizures, and focal neurologic deficits. CAA-RI can demonstrate characteristic brain MRI findings and can be reversed by steroids or other immunosuppressive therapies. Here, we report a case of CAA-RI, which was initially misdiagnosed as a subacute infarction but was diagnosed while reviewing follow-up brain MRI images, and spontaneous remission was achieved.

• Korean Journal of Plant Resources
• /
• v.26 no.4
• /
• pp.417-425
• /
• 2013

The aim of this study was to examine improving effect of Platycodon extracts (PE) and/or Platycodon extracts jelly (PEJ) on cognitive impairment in vitro and in vivo. PC12 (Pheochromocytoma) cells were pretreated with PE for 1hr and than incubated with $50{\mu}M$ amyloid ${\beta}(A{\beta})_{25-35}$ for additional 48hr. Cell viability was assessed by WST-1. Animals for Morris water test and passive avoidance test were divided into normal, control and two Platycodon extracts treated groups that were named Normal (n=7), Control (0 mg/kg, n=7), PE (300 mg/kg, n=7), PEJ (10 g/kg, n=7). Cognitive impairment was induced by scopolamine (1 mg/kg/body weight, i.p.) in the three experimental groups but not the normal group. Pretretment of PE (0.01-1 mg/mL) were not induced cytotoxicity but observed in high dose-treated group (5 and 10 mg/mL) in PC12 cells. Protective effects of PE against $A{\beta}$-induced cytotoxicity were increased in dose dependent manner in PC12 cells. Administration of PE and PEJ were significantly reduced escape latency time on Morris water maze test and passive avoidance test in copolamine-induced cognitive impairment animal model. These results suggest that Platycodon extracts and its related product available to ameliorative purpose for cognitive ability impairments.