• Biomolecules & Therapeutics
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• 제27권2호
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• pp.152-159
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• 2019

Multiple sclerosis (MS) is an autoimmune disease characterized by progressive neuronal loss, neuroinflammation, axonal degeneration, and demyelination. Previous studies have reported that 6-shogaol, a major constituent of ginger (Zingiber officinale rhizome), and its biological metabolite, 6-paradol, have anti-inflammatory and anti-oxidative properties in the central nervous system (CNS). In the present study, we investigated whether 6-shogaol and 6-paradol could ameliorate against experimental autoimmune encephalomyelitis (EAE), a mouse model of MS elicited by myelin oligodendrocyte glycoprotein ($MOG_{35-55}$) peptide immunization with injection of pertussis toxin. Once-daily administration of 6-shogaol and 6-paradol (5 mg/kg/day, p.o.) to symptomatic EAE mice significantly alleviated clinical signs of the disease along with remyelination and reduced cell accumulation in the white matter of spinal cord. Administration of 6-shogaol and 6-paradol into EAE mice markedly reduced astrogliosis and microglial activation as key features of immune responses inside the CNS. Furthermore, administration of these two molecules significantly suppressed expression level of tumor necrosis $factor-{\alpha}$, a major proinflammatory cytokine, in EAE spinal cord. Collectively, these results demonstrate therapeutic efficacy of 6-shogaol or 6-paradol for EAE by reducing neuroinflammatory responses, further indicating the therapeutic potential of these two active ingredients of ginger for MS.

• BMB Reports
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• 제54권6호
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• pp.295-304
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• 2021

Olfactory neuropathology is a cause of olfactory loss in Alzheimer's disease (AD). Olfactory dysfunction is also associated with memory and cognitive dysfunction and is an incidental finding of AD dementia. Here we review neuropathological research on the olfactory system in AD, considering both structural and functional evidence. Experimental and clinical findings identify olfactory dysfunction as an early indicator of AD. In keeping with this, amyloid-β production and neuroinflammation are related to underlying causes of impaired olfaction. Notably, physiological features of the spatial map in the olfactory system suggest the evidence of ongoing neurodegeneration. Our aim in this review is to examine olfactory pathology findings essential to identifying mechanisms of olfactory dysfunction in the development of AD in hopes of supporting investigations leading towards revealing potential diagnostic methods and causes of early pathogenesis in the olfactory system.

• Journal of Ginseng Research
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• 제45권3호
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• pp.420-432
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• 2021

Background: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. Methods: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. Results: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. Conclusion: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.

• Natural Product Sciences
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• 제28권3호
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• pp.153-160
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• 2022

Neuroinflammation is known to be associated with brain injury in Alzheimer's disease (AD), and the inhibition of microglial activation, a key player in inflammatory response, is considerd as important target for AD. In this study, the ethanol extract of aerial parts of Forsythia velutina Nakai, a Korean native species, significantly inhibited nitric oxide (NO) production in LPS-stimulated BV2 microglial cells. Thus, the active principles in F. velutina aerial parts were isolated based on activity-guided isolation method. As a result, six compounds were isolated and their structures were elucidated based on NMR data and the comparison with the relevant references as arctigenin (1), matairesinol (2), rengyolone (3), ursolic acid (4), secoisolariciresinol (5), and arctiin (6). Among them, four compounds including arctigenin (1), matairesinol (2), secoisolariciresinol (5), and arctiin (6) significantly inhibited NO production in a dose-dependent manner. In particular, matairesinol (2) and secoisolariciresinol (5) reduced 60% of NO production compared to LPS-treated group. This inhibitory effects of matairesinol (2) and secoisolariciresinol (5) were accompanied with the reduced expression levels of iNOS and COX-2. These results suggest that the extract of F. velutina and its active compounds could be beneficial for neuroinflammatory diseases including AD.

• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.297-305
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• 2021

Luteolin, a sort of flavonoid, has been reported to be involved in neuroprotective function via suppression of neuroinflammation. In this study, we investigated the protective effect of luteolin against oxidative stress-induced cellular senescence and its molecular mechanism using hydrogen peroxide (H₂O₂)-induced cellular senescence model in House Ear Institute-Organ of Corti 1 cells (HEI-OC1). Our results showed that luteolin attenuated senescent phenotypes including alterations of morphology, cell proliferation, senescence-associated 𝛽-galactosidase expression, DNA damage, as well as related molecules expression such as p53 and p21 in the oxidant challenged model. Interestingly, we found that luteolin induces expression of sirtuin 1 in dose- and time-dependent manners and it has protective role against H₂O₂-induced cellular senescence by upregulation of sirtuin 1 (SIRT1). In contrast, the inhibitory effect of luteolin on cellular senescence under oxidative stress was abolished by silencing of SIRT1. This study indicates that luteolin effectively protects against oxidative stress-induced cellular senescence through p53 and SIRT1. These results suggest that luteolin possesses therapeutic potentials against age-related hearing loss that are induced by oxidative stress.

• Natural Product Sciences
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• 제28권1호
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• pp.1-5
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• 2022

Two 2H-1-benzopyran derivatives, methyl 8-hydroxy-2,2-dimethyl-2H-1-benzopyran-5-carboxylate (1) and methyl 8-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carboxylate (2), including a new compound (1) were isolated from the twigs of Chaenomeles sinensis. Their chemical structures were characterized based on analysis of NMR data including ¹H and ¹³C, COSY, HSQC, and HMBC and HRMS data. The isolated compounds (1 and 2) were assessed for their anti-neuroinflammatory activity by measuring inhibition levels of nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells and for their neurotrophic activity by the secretion of nerve growth factor (NGF) in C6 cells. Compounds 1 and 2 exhibited powerful anti-neuroinflammatory effects with IC₅₀ values of 17.14 and 19.30 μM, respectively, without cell toxicity, and also showed moderate effects on the stimulation of NGF secretion levels with 113.15 ± 3.54 and 130.20 ± 8.03%, respectively. The biosynthetic pathway of 1 and 2 was proposed that they would be derived from a protocatechuic acid and an isoprenyl unit.

• Journal of Ginseng Research
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• 제47권4호
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• pp.506-514
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• 2023

Dementia has become one of the most important diseases threatening human health. Alzheimer's disease (AD) and vascular dementia (VaD) have the highest incidence rates among the types of dementia, but until now, therapeutic methods have been limited. Panax ginseng has been used in China for thousands of years to treat dementia, and modern medical studies have found that it contains multiple active components, such as ginsenosides, polysaccharides, amino acids, volatile oils and polyacetylenes, many of which have therapeutic effects in treating AD and VaD. Studies have found that ginsenosides have multitarget therapeutic effects in treating dementia, such as regulation of synaptic plasticity and the cholinergic system, inhibition of Aβ aggravation and tau hyperphosphorylation, anti-neuroinflammation, anti-oxidation effects and anti-apoptosis effects. Other active components of Panax ginseng, such as gintonin, oligosaccharides, polysaccharides and ginseng proteins, also have therapeutic effects on AD and VaD. The effectiveness of ginseng-containing Chinese medicine compounds has also been confirmed by clinical and basic investigations in treating AD and VaD. In this review, we summarized the potential therapeutic effects and related mechanisms of Panax ginseng in treating AD and VaD to provide some examples for further studies.

• 대한영상의학회지
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• 제81권3호
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• pp.488-500
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• 2020

최근의 연구들은 알츠하이머병의 병리가 단순히 아밀로이드와 타우단백질의 축적만이 아닌, 혈액뇌장벽(blood brain barrier; 이하 BBB) 이상과 같은 미세혈관병리와 밀접한 관련이 있음을 밝히고 있다. BBB 투과도 변화는 아밀로이드 및 타우 단백질 축적뿐 아니라 신경염증과 신경 퇴행성변화를 일으킴으로써 결국 임상 치매를 야기한다. 최근에는 알츠하이머 및 관련 질환의 BBB 이상을 보기 위한 MR 영상의 이용이 증가하고 있다. 이 종설에서는 알츠하이머병에서 BBB와 관련된 병리를 소개하고, BBB 투과도 변화에 대한 MR 영상 연구들을 소개할 것이다. 또한 BBB 투과도 측정을 위한 MR 방법론 개요와 문제점들을 제시할 것이다.

• Journal of Korean Neurosurgical Society
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• 제59권6호
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• pp.544-550
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• 2016

Objective : Cerebral endothelial cells have unique biological features and are fascinating candidate cells for stroke therapy. Methods : In order to understand the molecular mechanisms of human cerebral endothelial cell (hCMEC/D3) transplantation in a rat stroke model, we performed proteomic analysis using 2-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Protein expression was confirmed by quantitative real-time PCR and Western blot. Results : Several protein spots were identified by gel electrophoresis in the sham, cerebral ischemia (CI), and CI with hCMEC/D3 treatment cerebral ischemia with cell transplantation (CT) groups, and we identified 14 differentially expressed proteins in the CT group. Proteins involved in mitochondrial dysfunction (paraplegin matrix AAA peptidase subunit, SPG7), neuroinflammation (peroxiredoxin 6, PRDX6), and neuronal death (zinc finger protein 90, ZFP90) were markedly reduced in the CT group compared with the CI group. The expression of chloride intracellular channel 4 proteins involved in post-ischemic vasculogenesis was significantly decreased in the CI group but comparable to sham in the CT group. Conclusion : These results contribute to our understanding of the early phase processes that follow cerebral endothelial cell treatment in CI. Moreover, some of the identified proteins may present promising new targets for stroke therapy.

• 대한한의학방제학회지
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• 제25권4호
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• pp.471-481
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• 2017

Objectives : Noemyeong-san (NMS) is a novel herbal prescription composed of five oriental medicinal herbs including Prunellae Spica, Betulae Cortex, Foeniculi Fructus, Asiasari Radix, and Clematidis Radix for treating Alzheimer's disease. In the present study, we investigated the effects and molecular mechanisms of NMS on BV2 microglia to evaluate the potential action of this formula for preventing or treating neurodegenerative disease such as Alzheimer's disease. Methods : To determine the cytotoxicity of NMS on BV2 microglia, the MTT assay was performed. The effects of NMS on lipopolysaccharide (LPS)-stimulated BV2 microglia were determined with a nitric oxide (NO) assay and western blots for inflammatory mediator-related proteins, mitogen activated protein kinases (MAPKs), nuclear factor kappa B (NF-${\kappa}B$) pathway-related proteins, and heme oxygenase-1 (HO-1). Result : NMS inhibited induction of iNOS and COX-2 as well as NO production without affecting the cell viability in LPS-stimulated BV2 microglia. NMS also suppressed activation of ERK and p38 MAPK among main kinases of MAPKs as well as NF-${\kappa}B$ by LPS stimulation. Furthermore, NMS dose-dependently induced the expression of HO-1 and the inhibitory effect of NMS on the production of NO were blocked by pretreatment with an HO-1 inhibitor, Snpp. Conclusions : These results demonstrate that NMS has potent anti-neuroinflammatory effect on the LPS-stimulated microglia. These findings provide evidences for NMS to be considered as a new prescription for preventing or treating neurodegenerative disease such as Alzheimer's disease.