• Journal of Microbiology and Biotechnology
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• v.32 no.9
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• pp.1154-1167
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• 2022

In this study, we investigated the anti-amnesic effect of Korean red pine (Pinus densiflora) bark extract (KRPBE) against amyloid beta_1-42 (Aβ_1-42)-induced neurotoxicity. We found that treatment with KRPBE improved the behavioral function in Aβ-induced mice, and also boosted the antioxidant system in mice by decreasing malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. In addition, KRPBE improved the cholinergic system by suppressing reduced acetylcholine (ACh) content while also activating acetylcholinesterase (AChE), regulating the expression of choline acetyltransferase (ChAT), postsynaptic density protein-95 (PSD-95), and synaptophysin. KRPBE also showed an ameliorating effect on cerebral mitochondrial deficit by regulating reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and ATP levels. Moreover, KRPBE modulated the expression levels of neurotoxicity indicators Aβ and phosphorylated tau (p-tau) and inflammatory cytokines TNF-α, p-IκB-α, and IL-1β. Furthermore, we found that KRPBE improved the expression levels of neuronal apoptosis-related markers BAX and BCl-2 and increased the expression levels of BDNF and p-CREB. Therefore, this study suggests that KRPBE treatment has an anti-amnestic effect by modulating cholinergic system dysfunction and neuroinflammation in Aβ_1-42-induced cognitive impairment in mice.

• Yonsei Medical Journal
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• v.59 no.9
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• pp.1096-1106
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• 2018

Purpose: Alzheimer's disease (AD) is the sixth most common cause of death in the United States. MicroRNAs have been identified as vital players in neurodegenerative diseases, including AD. microRNA-128 (miR-128) has been shown to be dysregulated in AD. This study aimed to explore the roles and molecular mechanisms of miR-128 in AD progression. Materials and Methods: Expression patterns of miR-128 and peroxisome proliferator-activated receptor gamma ($PPAR-{\gamma}$) messenger RNA in clinical samples and cells were measured using RT-qPCR assay. $PPAR-{\gamma}$ protein levels were determined by Western blot assay. Cell viability was determined by MTT assay. Cell apoptotic rate was detected by flow cytometry via double-staining of Annexin V-FITC/PI. Caspase 3 and $NF-{\kappa}B$ activity was determined by a Caspase 3 Activity Assay Kit or $NF-{\kappa}B$ p65 Transcription Factor Assay Kit, respectively. Bioinformatics prediction and luciferase reporter assay were used to investigate interactions between miR-128 and $PPAR-{\gamma}$ 3'UTR. Results: MiR-128 expression was upregulated and $PPAR-{\gamma}$ expression was downregulated in plasma from AD patients and $amyloid-{\beta}$ $(A{\beta})-treated$ primary mouse cortical neurons (MCN) and Neuro2a (N2a) cells. Inhibition of miR-128 decreased $A{\beta}-mediated$ cytotoxicity through inactivation of $NF-{\kappa}B$ in MCN and N2a cells. Moreover, $PPAR-{\gamma}$ was a target of miR-128. $PPAR-{\gamma}$ upregulation attenuated $A{\beta}-mediated$ cytotoxicity by inactivating $NF-{\kappa}B$ in MCN and N2a cells. Furthermore, $PPAR-{\gamma}$ downregulation was able to abolish the effect of anti-miR-128 on cytotoxicity and $NF-{\kappa}B$ activity in MCN and N2a cells. Conclusion: MiR-128 inhibitor decreased $A{\beta}-mediated$ cytotoxicity by upregulating $PPAR-{\gamma}$ via inactivation of $NF-{\kappa}B$ in MCN and N2a cells, providing a new potential target in AD treatment.

• Journal of Oriental Neuropsychiatry
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• v.18 no.2
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• pp.13-24
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• 2007

Objective : Recent studies indicate that the deposition of ${\beta}-amyloid$ ($A{\beta}$) is related in the pathogenesis of Alzheimer's disease (AD), but the underlying mechanism is still not clear. Method : To investigate the potential cellular functions of APP and water extract of the JangwonHwangagambang (JWHG), we use as in vitro model, neuro 2A cells were treated with either JWHG or its oriental medicines, and the effect in APP expression was determined by MTT and LDH assay. JWHG have been shown to be neuroprotective in different model systems. We asked whether JWHG treatment would influence cell survival and AD-like pathology in APP-induced neuronal cells. Result : JWHG and water extracts of some oriental medicine has attenuated high cell death in vitro. JWHG-treated cells increased percentage of cell survival more longly than controls. JWHG had significantly increas neurite outgrowth in the as compared to control cells. Conclusion : These results suggest that JWHG prevent APP-induced neurotoxicity through attenuating oxidative stress, and may be useful as potential therapeutic agents for AD.

• Journal of Oriental Neuropsychiatry
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• v.19 no.2
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• pp.151-163
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• 2008

Objective : Recent studies indicate that the deposition of beta-amyloid ($A{\beta}$) is related in the pathogenesis of Alzheimer's disease (AD), but the underlying mechanism is still not clear. Method : To investigate the potential cellular functions of APP and LMK02, we use transgenic drosophila as a model was treated with either LMK02, and the effect in APP expression was determined by climbing assay. LMK02 have been shown to be neuroprotective in fly model systems. We asked whether dietary supplementation with LMK02 would influence behavior and AD-like pathology in a transgenic fly model. Result LMK02 water extract have attenuated fly death in vivo. LMK02-treated fly increased percentage of flight ability more longly and survival ratio more than controls. APP-GRIM drosophila treated with LMK02 had significantly less accumulation of APP deposition in the eye and brain as compared to control drosophila. Conclusion : These results suggest that LMK02 prevent APP-induced neurotoxicity through attenuating flies death induced by APP, and may be useful as potential therapeutic agents for AD.

• Food Science and Biotechnology
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• v.15 no.5
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• pp.735-738
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• 2006

We examined the neuroprotective and neurotrophic effects of genipin fractionated from gardenia (Gardenia jasminoides Ellis) originating from Korea. The neurotrophic effects of the genipin containing fraction was evaluated by microscopically monitoring its potency to induce neurite outgrowth in PC12h cells. The genipin containing fraction from Korean gardenia promoted neurite outgrowth in PC12h cells in this study, similar to previously reported effects by Wako Chemical, Japan. When cells were treated with the genipin containing fraction prior to ${\beta}$-amyloid peptide treatment (active domain of A peptide 25-35 treated), toxicity was significantly diminished (p<0.0l). These results suggest that genipin prepared from Korean gardenia might potentially be used as a precautionary agent in neurodegenerative disease, such as Alzheimer's disease, etc.

• Journal of Microbiology and Biotechnology
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• v.21 no.8
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• pp.854-857
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• 2011

POMT7, which is an O-methyltransferase from poplar, transfers a methyl group to several flavonoids that contain a 7-hydroxyl group. POMT7 has been shown to have a higher affinity toward quercetin, and the reaction product rhamnetin has been shown to inhibit the formation of beta-amyloid. Thus, rhamnetin holds great promise for use in therapeutic applications; however, methods for mass production of this compound are not currently available. In this study, quercetin was biotransformed into rhamnetin using Escherichia coli expressing POMT7, with the goal of developing an approach for mass production of rhamnetin. In order to maximize the production of rhamnetin, POMT7 was subcloned into four different E. coli expression vectors, each of which was maintained in E. coli with a different copy number, and the best expression vector was selected. In addition, the S-adenosylmethionine biosynthesis pathway was engineered for optimal cofactor production. Through the combination of optimized POMT7 expression and cofactor production, the production of rhamnetin was increased up to 111 mg/l, which is approximately 2-fold higher compared with the E. coli strain containing only POMT7.

• The Korea Journal of Herbology
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• v.22 no.1
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• pp.7-12
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• 2007

Objectives : In Alzheimer's disease(AD), free radical oxidative stress caused by amyloid beta-peptide may lead to DNA damage, neuronal dysfunction, neurotoxicity and cell death, Hwangryunhaedok-tang(HHT) is traditionally used for the treatment of pyrogenetic diseases. To develop a new anti-AD drug from natural herb, HHT was selected and extracted in this study. Methods : The antioxidant activities of HHT water extract powder were examined by hydroxyl radical-induced DNA strand nicking assay, and antioxidative enzymes expression assay in H4IIE cell. In addition, HHT was examined for the inhibitory effect on the acetylcholinesterase(AChE) using by Ellman's coupled assay. Results: The HHT exhibit DNA protective effect in the hydroxyl radical-induced DNA Strand nicking assay, mRNA expression of superoxide dismutase and glutathione peroxidase were recovered at a normal level by HHT treatment in H4IIE cell. Furthermore, water extract of HHT showed inhibitory effect on AChE activity. Conclusion : These results suggest that HHT may be effective in delaying and preventing AD progression related to the free radical-induced DNA damage and AChE activity.

• The Korean Journal of Food And Nutrition
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• v.27 no.4
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• pp.673-677
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• 2014

HX106N은 용안육, 맥문동, 단삼 및 천마 등의 4가지 식물로 구성된 추출물로서, 선행 연구에서 amyloid ${\beta}$ peptide에 의한 생쥐의 기억력 저하 및 산화 손상을 억제하는 것으로 밝혀졌다. 이 연구에서는 HX106N이 비선택적 무스카린 수용체 길항제로 잘 알려진 스코폴라민(scopolamine)으로 유도한 콜린성 건망증(cholinergic amnesia)에 어떤 영향을 미치는지를 평가하였다. ICR 생쥐에게 스코폴라민(1 mg/kg body weight, i.p.)을 주입하기 1시간 전에 HX106N(100 mg/kg body weight, p.o.)을 투여하였다. 30분 후 수행한 Y-미로 시험(Y-maze test) 및 수동 회피 시험(passive avoidance test)에서 HX106N는 스코폴라민에 의해 감소되는 자발적 변경 행동(spontaneous alternation) 및 지체시간(step-through latency)을 유의미하게 억제하여 건망증을 개선시키는 것으로 나타났다. 또한 HX106N을 투약 1시간 후 생쥐의 해마와 대뇌피질 부위의 아세틸콜린에스테라제(acetylcholinesterase; AChE)의 활성을 측정한 결과 통계적으로 유의미한 정도의 활성 감소가 관찰되었다. 이러한 결과들을 종합할 때 HX106N은 AD에서 관찰되는 콜린성신경전달 장애로 인한 기억력 저하 억제에 사용될 수 있는 가능성을 가진 것으로 판단된다.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.108-108
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• 2002

Mutations in the presenilin genes (PS-1 and PS-2) are linked to early onset familial Alzheimer's disease(AD), but its underlying cellular mechanisms have not been clear. 15-Deoxy-Δ12, 14-prostaglandin J2 (15-deoxy-PGJ2) is know as a naturally occurring ligand of the peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$).(omitted)

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.431-437
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• 2011

Recently, there are so many studies that herbal composition has the effect on enhancing the memorial ability. But there are few studies whether it has effect on enhancing attentional ability. The purpose of present study is to prove the effects of a herbal composition(ChongA 100) on enhancing not only memorial but also attentional ability. The memorial ability interfered by amyloid-${\beta}$ was evaluated with passive avoidance test Y-maze task. The attentional ability was studied with attentional set-shifting task(ASST). The 200mg/kg of ChongA100 could significantly recover the shortened latency of passive avoidance test and the interfered alternation of Y-maze task. The number of trials in ASST was significantly reduced as well. Our study suggests that it has effects on enhancing both memorial and attentional ability.