• Journal of the Korean Society of Food Science and Nutrition
• /
• v.42 no.4
• /
• pp.595-599
• /
• 2013

Alzheimer's disease is a progressive neurodegenerative disorder characterized by a gradual decline in memory associated with shrinkage of brain tissue, with a localized loss of neurons mainly in the hippocampus and basal forebrain. This study investigated the neuroprotective effect of Gastrodia elata aqueous extracts against scopolamine-induced neurotoxicity in the hippocampus of male Sprague-Dawley rats. The animals (n=25) were divided into five different groups with five animals per each group. The normal group (Nor) was administered with saline, while the control (Con) group was administered saline after scopolamine treatment. The experimental group (Exp) was administered Gastrodia elata aqueous extracts (200 mg/kg body weight) for 20 or 30 days after scopolamine treatment. From a light microscopy study, the nuclei of neurons in the hippocampus were more shrunken or condensed in the 20 or 30 day control groups compared to experimental groups. The densities of neurons from the CA1 and CA3 area of the hippocampus in the Exp increased compared with the Con. Amyloid ${\beta}$ protein, containing PAS-positive materials, was lower in the Exp compared with the Con. The present study demonstrates that Gastrodia elata aqueous extracts possess neuroprotective potential, thus validating its use in alleviating the toxic effects of scopolamine.

• The Korean Journal of Physiology and Pharmacology
• /
• v.24 no.4
• /
• pp.299-310
• /
• 2020

Alzheimer's disease (AD) is a multi-faceted neurodegenerative disease. Thus, current therapeutic strategies require multitarget-drug combinations to treat or prevent the disease. At the present time, single drugs have proven to be inadequate in terms of addressing the multifactorial pathology of AD, and multitarget-directed drug design has not been successful. Based on these points of views, it is judged that combinatorial drug therapies that target several pathogenic factors may offer more attractive therapeutic options. Thus, we explored that the combination therapy with lower doses of cilostazol and aripiprazole with add-on donepezil (CAD) might have potential in the pathogenesis of AD. In the present study, we found the superior efficacies of donepezil add-on with combinatorial mixture of cilostazol plus aripiprazole in modulation of expression of AD-relevant genes: Aβ accumulation, GSK-3β, P300, acetylated tau, phosphorylated-tau levels, and activation of α-secretase/ADAM 10 through SIRT1 activation in the N2a Swe cells expressing human APP Swedish mutation (N2a Swe cells). We also assessed that CAD synergistically raised acetylcholine release and choline acetyltransferase (CHAT) expression that were declined by increased β-amyloid level in the activated N2a Swe cells. Consequently, CAD treatment synergistically increased neurite elongation and improved cell viability through activations of PI3K, BDNF, β-catenin and α7-nicotinic cholinergic receptors in neuronal cells in the presence of Aβ_1-42. This work endorses the possibility for efficient treatment of AD by supporting the synergistic therapeutic potential of donepezil add-on therapy in combination with lower doses of cilostazol and aripiprazole.

• The Journal of Korean Medicine
• /
• v.26 no.3 s.63
• /
• pp.27-42
• /
• 2005

Objectives : Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease characterized by amyloid plaques and neurofibrillary tangles. These plaques are associated with degenerating neuronal processes and consist primarily of fibrillary aggregates of beta-amyloid$ protein, generated from amyloid precursor protein (APP). Another amyloidogenic fragment, the carboxyl terminus (CT) of APP, which is composed of 99-105 amino acid residues containing the complete $A{\beta}$ sequence, also appears to be toxic to neurones. Recent evidence suggest that CT105, carboxy terminal 105 amino acids peptide fragment of APP, may be an important factor causing neurotoxicity in AD. Methods : Although a variety of oriental prescriptions including Pinelliae rhizoma have traditionally been utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. In the present study, we investigated effects of the dichloromethane extract of Pinelliae rhizoma (PINR) on neurotoxicity and the formation of reactive oxygen species (ROS) and nitric oxide (NO) in SK-N-SH cells overexpressed with CT105. In addition, we evaluated its radical scavenging activity and effects on acetylcholinesterase (AChE) activity. Furthermore, effects on cognitive deficits induced by scopolamine treatment in rats were evaluated. Results ; We found in this study that PINR significantly inhibited apoptotic neuronal death induced by CT105 overexpression in SK-N-SH cells. Based on morphological examinations by phase-contrast microscopy, PINR reversed apoptotic changes of CT105-expressed cells. It was also found that PINR significantly promoted neurite outgrowth and inhibited formation of ROS nd NO. PINR was shown to scavenge DPPH radicals and noncompetitively inhibit AChE activity. Furthermore, it reduced scopolamine-induced memory impairment in rata, assessed by passive avoidance test. Conclusions : Taken together, these results demonstrate that PINR exhibits neuroprotective, antioxidant, and memory enhancing effects, and therefore may bs beneficial for the treatment of AD.

• Korean Journal of Food Science and Technology
• /
• v.47 no.6
• /
• pp.779-784
• /
• 2015

This study was conducted to investigate the effect of herbs on memory improvement by focusing on their cholinergic functions in Tg2576 mice. Seven herbs were used to obtain extracts by using alcohol and water. In screening test for cholinergic activities of the extracts, acetylcholinesterase (AChE) activity was highly inhibited in Oenanthe javanica alcohol extract (OJAE, 18.76%) as compared with the others. The OJAE-treated Tg2576 (Tg-OJAE) groups showed the statistically significant increases of latency time in passive avoidance test. Also, it was found that the concentration of $A{\beta}1-42$ was significantly reduced in Tg-OJAE groups compared to non-treated Tg2576 groups. In the additional enzyme test, it was found that $IC_{50}$ of OJAE was $991.77{\mu}g/mL$ and OJAE acted as an uncompetitive inhibitor of AChE. Therefore, it seemed that OJAE can be used for the development of processed foods for memory improvement.

• Journal of Ginseng Research
• /
• v.46 no.3
• /
• pp.464-472
• /
• 2022

Background: Gut microbiota influence the central nervous system through gut-brain-axis. They also affect the neurological disorders. Gut microbiota differs in patients with Alzheimer's disease (AD), as a potential factor that leads to progression of AD. Oral intake of Korean Red Ginseng (KRG) improves the cognitive functions. Therefore, it can be proposed that KRG affect the microbiota on the gut-brain-axis to the brain. Methods: Tg2576 were used for the experimental model of AD. They were divided into four groups: wild type (n = 6), AD mice (n = 6), AD mice with 30 mg/kg/day (n = 6) or 100 mg/kg/day (n = 6) of KRG. Following two weeks, changes in gut microbiota were analyzed by Illumina HiSeq4000 platform 16S gene sequencing. Microglial activation were evaluated by quantitative Western blot analyses of Iba-1 protein. Claudin-5, occludin, laminin and CD13 assay were conducted for Blood-brain barrier (BBB) integrity. Amyloid beta (Aβ) accumulation demonstrated through Aβ 42/40 ratio was accessed by ELISA, and cognition were monitored by Novel object location test. Results: KRG improved the cognitive behavior of mice (30 mg/kg/day p < 0.05; 100 mg/kg/day p < 0.01), and decreased Aβ 42/40 ratio (p < 0.01) indicating reduced Aβ accumulation. Increased Iba-1 (p < 0.001) for reduced microglial activation, and upregulation of Claudin-5 (p < 0.05) for decreased BBB permeability were shown. In particular, diversity of gut microbiota was altered (30 mg/kg/day q-value<0.05), showing increased population of Lactobacillus species. (30 mg/kg/day 411%; 100 mg/kg/day 1040%). Conclusions: KRG administration showed the Lactobacillus dominance in the gut microbiota. Improvement of AD pathology by KRG can be medicated through gut-brain axis in mice model of AD.

• Journal of Life Science
• /
• v.30 no.12
• /
• pp.1118-1127
• /
• 2020

Alzheimer's disease causes progressive neuronal loss that leads to cognitive disturbances. It is not currently curable, and there is no way to stop its progression. However, since medical treatment for Alzheimer's disease is most effective in the early stages, early detection can provide the best chance for symptom management. Biomarkers for the diagnosis of Alzheimer's disease include amyloid β (Aβ) deposition, pathologic tau, and neurodegeneration. Aβ deposition and phosphorylated tau can be detected by cerebrospinal fluid (CSF) analysis or positron emission tomography (PET). However, CSF sampling is quite invasive, and PET analysis needs specialized and expensive equipment. During the last decades, blood-based biomarker analysis has been studied to develop fast and minimally invasive biomarker analysis method. And one of the remarkable findings is the involvement of platelets as a primary source of Aβ in plasma. Aβ can be transported across the blood - brain barrier, creating an equilibrium of Aβ levels between the brain and blood under normal condition. Interestingly, a number of clinical studies have unequivocally demonstrated that plasma Aβ42/Aβ40 ratios are reduced in mild cognitive impairment and Alzheimer's disease. Together, these recent findings may lead to the development of a fast and minimally invasive early diagnostic approach to Alzheimer's disease. In this review, we summarize recent advances in the biomarkers of Alzheimer's disease, especially the involvement of platelets as a source of peripheral Aβ production and its potential as a blood-based biomarker.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.20 no.2
• /
• pp.42-45
• /
• 2016

Purpose Neuracep is used to other diagnostic evaluations of the brain to estimate beta-amyloid neuritic plaque density in adult patients with cognitive impairment and inspected cognitive impairment. $^{18}F-Florbetaben$ specially has moderate lipophilicity and property of the added ethanol. It is the subject of interest of the patient pain and residual activity after injecting. Our study is effective injection method of the radiopharmaceutical and patient care. So it is for the highest quality image. Materials and Methods Patients were targeted 70 subjects, it was injected mean $259{\pm}74MBq$ to the patients ($^{18}F-FDG$: 20 subjects, $^{18}F-FP-CIT$: 20 subjects, $^{18}F-Florbetaben$: 30 subjects). After injection (reflusing 2 times, reflusing 3 times) using a 3-way set, it measured the residual activity. When injecting $^{18}F-Florbetaben$, we evaluated the effective injection methods(3-way set method and heparin cap method). The average residual activity after the injection was compared using a statistical analysis of SPSS 12.0(ANOVA, t-test analysis). Also, elemental analysis was performed on $^{18}F-Florbetaben$ by GC (Gas Chromatography). Results When reflusing 2 times measured residual activity as follows ($^{18}F-FDG$: 1.48 MBq, $^{18}F-FP-CIT$: 7.4 MBq, $^{18}F-Florbetaben$: 32.6 MBq). And when reflusing 3 times measured residual activity as follows ($^{18}F-FDG$: 1.85 MBq, $^{18}F-FP-CIT$: 3.7 MBq, $^{18}F-Florbetaben$: 36.3 MBq). There was a significant difference when reflusing 2 times(P < 0.05) and reflusing 3 times (P < 0.05). But when reflusing 3 times, there was no significant difference relation FDG and FP-CIT (P > 0.05). $^{18}F-Florbetaben$ Residual activity according to the injection method was a significant difference (P < 0.05). GC analysis results were measured ethanol: 207665 ppm and acceton: 377.4 ppm. Conclusion $^{18}F-Florbetaben$ was high residual activity compared to FDG and FP-CIT. Heparin cap method was effective when $^{18}F-Florbetaben$ was injected. $^{18}F-Florbetaben's$ ethanol component analysis was highly measured. So it is recommended that inject to 6 sec/ml or more in order to reduce the pain.