• Preventive Nutrition and Food Science
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• v.12 no.2
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• pp.74-78
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• 2007

Fucoidan, that is high-molecular-weight sulfated polysaccharides extracted from brown seaweeds has been shown to elicit various biological activities. Here, we investigated the effects of fucoidan on cell proliferation and nitric oxide (NO) production in neuronal blastoma cell (SH-SY5Y). In the present study, we demonstrated that fucoidan treatment resulted in increase of cell proliferation and NO production. When cells were treated with amyloid-${\beta}$ (A${\beta}$) in the absence or presence of fucoidan, fucoidan recovered the cell viability decreased by A${\beta}$ peptides. To further determine whether nitric oxide synthase (NOS) is involved in proliferative effect of fucoidan, cells were treated with NOS inhibitors in the absence or presence of fucoidan. Selective constitutive nitric oxide synthase (cNOS) inhibitor, diphenylene iodonium chloride (DPI), caused a decrease of cell viability, whereas cell viability was increased by specific inducible nitric oxide synthase (iNOS) inhibitor, S-methylisothiourea (SMT), in the fucoidan-untreated cells. Treatment with fucoidan inhibited the cell viability decreased in DPI-exposed cells. In contrast, fucoidan had no effect on cell growth in SMT-treated cells, indicating that cNOS may not play a role in the proliferation of fucoidan-treated cells. The present data suggest that fucoidan has proliferative and neuroprotective effects and these effects may be associated with iNOS.

• Molecules and Cells
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• v.21 no.2
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• pp.244-250
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• 2006

Gangliosides are receptors for various peptides and proteins including neuropeptides, ${\beta}$-amyloid proteins, and prions. Recently, the role of gangliosides in mucosal immunization has attracted attention due to the emerging interest in oral vaccination. Ganglioside GM1 exists in abundance on the surface of the M cells of Peyer's patch, a well-known mucosal immunity induction site. In the present study we identified a peptide ligand for GM1 and tested whether it played a role in immune induction. GM1-binding peptides were selected from a phage-displayed dodecapeptide library and one peptide motif, GWKERLSSWNRF, was fused to the C-terminus of enhanced green fluorescent protein (EGFP). The fusion protein, but not EGFP fused with a control peptide, was concentrated around Peyer's patch after incubation in the lumen of the intestine ex vivo. Furthermore, oral feeding of the fusion protein but not control EGFP induced mucosal and systemic immune responses against EGFP resembling Th2-type immune responses.

• Nutrition Research and Practice
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• v.17 no.6
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• pp.1128-1142
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• 2023

BACKGROUND/OBJECTIVES: Inonotus obliquus has been used as antidiabetic herb around the world, especially in the Russian and Scandinavian countries. Diabetes is widely believed to be a key factor in Alzheimer's disease (AD), which is widely considered to be type III diabetes. To investigate whether I. obliquus can also ameliorate AD, it would be interesting to identify new clues for AD treatment. We tested the anti-AD effects of raw Inonotus obliquus polysaccharide (IOP) in a mouse model of AD (3×Tg-AD transgenic mice). MATERIALS/METHODS: SPF-grade 3×Tg-AD mice were randomly divided into three groups (Control, Metformin, and raw IOP groups, n = 5 per group). β-Amyloid deposition in the brain was analyzed using immunohistochemistry for AD characterization. Gene and protein expression of pertinent factors of the ubiquitin-proteasome system (UPS) was determined using real-time quantitative polymerase chain reaction and Western blotting. RESULTS: Raw IOP significantly reduced the accumulation of amyloid aggregates and facilitated UPS activity, resulting in a significant reduction in AD-related symptoms in an AD mouse model. The presence of raw IOP significantly enhanced the expression of ubiquitin, E1, and Parkin (E3) at both the mRNA and protein levels in the mouse hippocampus. The mRNA level of ubiquitin carboxyl-terminal hydrolase isozyme L1, a key factor involved in UPS activation, also increased by approximately 50%. CONCLUSIONS: Raw IOP could contribute to AD amelioration via the UPS pathway, which could be considered as a new potential strategy for AD treatment, although we could not exclude other mechanisms involved in counteracting AD processing.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.1-14
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• 2009

Objectives : Alzheimer's disease (AD) is characterized by neuronal loss and extracellular senile plaque. Moreover, the cellular actions of ${\beta}$-amyloid (A${\beta}$ play a causative role in the pathogenesis of AD. This study was designed to determine whether Woo-Gui-Um, a commonly used Korean herbal medicine, has the ability to protect cortical and hippocampal neurons against A${\beta}_{25-35}$ neurotoxicity Methods : In the present study, the authors investigated the preventative effects of the water extract of Woo-Gui-Um in a mouse model of AD. Memory impairment was induced by intraventricularly (i.c.v.) injecting A${\beta}_{25-35}$ peptides into mice. Woo-Gui-Um extract was then administered orally (p.o.) for 14 days. In addition, A${\beta}_{25-35}$ toxicity on the hippocampus was assessed immunohistochemically, by staining for Tau, MAP2, TUNEL, and Bax, and by performing an in vitro study in PC12 cells. Results : Woo-Gui-Um extract had an effect to improve learning ability and memory score in the water maze task. Woo-Gui-Um extract had significant neuroprotective effects in vivo against oxidative damage and apoptotic cell death of hippocampal neurons caused by i.c.v. A${\beta}_{25-35}$. In addition, Woo-Gui-Um extract was found to have a protective effect on A${\beta}_{25-35}$-induced apoptosis, and to promote neurite outgrowth of nerve growth factor (NGF)-differentiated PC12 cells. Conclusions : These results suggest that Woo-Gui-Um extract reduces memory impairment and Alzheimer's dementia via an anti-apoptotic effect and by regulating Tau and MAP2 in the hippocampus.

• Journal of Life Science
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• v.18 no.6
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• pp.796-803
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• 2008

Mutations in the APP gene lead to enhanced cleavage by ${\beta}-$ and ${\gamma}-secretase$, and increased $A{\beta}$ formation, which are closely associated with Alzheimer's disease (AD)-like neuropathological changes. Recent studies have shown that exercise training can ameliorate pathogenic phenotypes ($A{\beta}-42$, BDNF, GLUT-1 and HSP70) in experimental models of Alzheimer's disease. Here, we have used NSE/APPsw transgenic mice to investigate directly whether exercise training ameliorates pathogenic phenotypes within Alzheimer's brains. Sixteen weeks of exercise training resulted in a reduction of $A{\beta}-42$ peptides and also facilitated improvement of cognitive function. Furthermore, GLUT -1 and BDNF proteins produced by exercise training may protect brain neurons by inducing the concomitant expression of genes that encode proteins (HSP-70) which suppress stress induced neuron cell damages from APPsw transgenic mice. Thus, the improved cognitive function by exercise training may be mechanistically linked to a reduction of $A{\beta}-42$ peptides, possibly via activation of BDNF, GLUT-1, and HSP-70 proteins. On the basis of the evidences presented in this study, exercise training may represent a practical therapeutic management strategy for human subjects suffering from Alzheimer's disease.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.45-49
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• 2005

Background: Inflammation in the brain has known to be associated with the development of a various neurological diseases. The hallmark of neuro-inflammation is the activation of microglia, brain macrophage. Pro-inflammatory compounds including nitric oxide (NO) are the main cause of neuro-degenerative disease such as Alzheimer's disease (AD) which is resulted in cell death. Among those pro-inflammatory compounds, NO contributes to the cell death by directly or indirectly. Methods: In the study, we examined whether ursodeoxycholic acid (UDCA), a non-toxic hydrophilic bile acid, inhibits the NO production by a direct method using Griess reagent and by RT-PCR in the gene expression of inducible nitric oxide synthase (iNOS). In signal transduction, we also examined the NF-${\kappa}B$ (p65/p50), IKK, and I ${\kappa}B$, which are associated with the expression of iNOS gene using western blots. Results: In the present study, we found that UDCA effectively inhibited NO production in BV-2 microglial cell, and NF-${\kappa}B$ activation was reduced by suppressing IKK gene expression and by increasing the I${\kappa}B$ in cytosol comparing those to the positive control LPS. Conclusion: Taken together, these data suggested that UDCA may playa crucial role in inhibiting the NO production and the results imply that UDCA suppresses a cue signal of the microglial activation via stimulators, such as ${\beta}$-amyloid peptides which are known to stimulate microglia in AD pathogenesis.

• Journal of the Korean Society of Radiology
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• v.84 no.3
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• pp.638-652
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• 2023

Purpose To investigate the MRI markers for the prediction of amyloid β (Aβ)-positivity in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to evaluate the differences in MRI markers between Aβ-positive (Aβ [+]) and -negative groups using the machine learning (ML) method. Materials and Methods This study included 139 patients with MCI and AD who underwent amyloid PET-CT and brain MRI. Patients were divided into Aβ (+) (n = 84) and Aβ-negative (n = 55) groups. Visual analysis was performed with the Fazekas scale of white matter hyperintensity (WMH) and cerebral microbleeds (CMB) scores. The WMH volume and regional brain volume were quantitatively measured. The multivariable logistic regression and ML using support vector machine, and logistic regression were used to identify the best MRI predictors of Aβ-positivity. Results The Fazekas scale of WMH (p = 0.02) and CMB scores (p = 0.04) were higher in Aβ (+). The volumes of hippocampus, entorhinal cortex, and precuneus were smaller in Aβ (+) (p < 0.05). The third ventricle volume was larger in Aβ (+) (p = 0.002). The logistic regression of ML showed a good accuracy (81.1%) with mini-mental state examination (MMSE) and regional brain volumes. Conclusion The application of ML using the MMSE, third ventricle, and hippocampal volume is helpful in predicting Aβ-positivity with a good accuracy.