• 동의생리병리학회지
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• 제18권1호
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• pp.254-259
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• 2004

Jeongshin-tang (JST) is a Korean herbal prescription, which has been successfully applied for the various neuronal diseases. However, it's effect remains unknown in experimental models. To investigate the biological effect of JST in Alzheimer's disease (AD) in vitro model, we analized the production of interleukin (IL)-6 and IL-8, and expression of cyclooxygenase (COX)-2 in IL-1β plus β-amyloid [25-35] fragment (A)-stimulated human astrocytoma cell line U373MG. JST alone had no effect on the cell viability. The production of IL-6 and IL-8 was significantly inhibited by pretreatment with JST (1mg/㎖) on IL-1β plus A-stimulated U373MG cells. Maximal inhibition rate of IL-6 and IL-8 production by JST was about 41.22% (P<0.01) and 34.45% (P<0.05), respectively. The expression level of COX-2 protein was up-regulated by IL-1β plus A but the increased level of COX-2 was inhibited by pretreatment with JST (1 mg/㎖). These data indicate that JST has a regulatory effect on cytokine production and COX-2 expression, which might explain it's beneficial effect in the treatment of AD.

• BMB Reports
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• 제43권6호
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• pp.413-418
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• 2010

Beta-Amyloid ($A{\beta}$)-induced neuroinflammation is one of the key events in the development of neurodegenerative disease. We previously reported that KHG21834, a benzothiazole derivative, attenuates $A{\beta}$-induced degeneration of cortical and mesencephalic neurons in vitro. In the present work, we show that KHG21834 reduces $A{\beta}$-mediated neuroinflammation in brain. In vivo intracerebroventricular infusion of KHG21834 leads to decreases in the numbers of activated astrocytes and microglia and level of proinflammatory cytokines such as interleukin-$1{\beta}$ and tumor necrosis factor-$\alpha$ induced by $A{\beta}$ in the hippocampus. This suppression of neuroinflammation is associated with decreased neuron loss, restoration of synaptic dysfunction biomarkers in the hippocampus to control level, and diminished amyloid deposition. These results may suggest the potential therapeutic efficacy of KHG21834 for the treatment of $A{\beta}$-mediated neuroinflammation.

• 한국컴퓨터정보학회논문지
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• 제25권6호
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• pp.165-170
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• 2020

본 논문에서는 스코폴레틴이 알츠하이머병 신경염증보호제로서의 가능성을 제안하기 위해 미세아교세포 BV-2에서 아밀로이드베타 올리고머(Aβ_1-42)로 유도된 염증을 억제하는지 확인하였다. 또한, 염증관련 사이토카인 및 염증매개인자가 어떠한 메커니즘으로 조절되는지 확인하였다. 알츠하이머병은 가장 흔한 신경 퇴행성 질환이지만, 특정 병인을 알 수 없는 질환이며, 이를 해결하기 위해 많은 연구에서 노력을 기울이고 있다. 우리는 먼저 스코폴레틴과 Aβ_1-42가 BV-2 세포에 독성을 보이는지 확인하기 위해 CCK-8 assay 방법으로 세포 생존율을 측정하였다. Western Blot을 통해 Aβ_1-42로 유도된 염증반응에서 interleukin 1 beta (IL-1β), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nuclear factor-κB (NF-κB)의 발현정도를 분석하였다. ANOVA 분석법을 통해 Aβ_1-42를 단독 처리한 BV-2 세포와 스코폴레틴을 전 처리한 BV-2 세포에서 단백질 발현 차이를 비교하였다. 그 결과 스코폴레틴을 전 처리한 BV-2 세포에서 IL-1β, COX-2, iNOS, NF-κB 발현수준이 유의미하게 감소되었다 (p value < 0.05). 따라서 본 연구는 향후 스코폴레틴이 알츠하이머병의 신경염증보호제로서 개발 가치가 있음을 제시하였다.

• Journal of Applied Biological Chemistry
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• 제62권4호
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• pp.327-332
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• 2019

알츠하이머 질환(Alzheimer's disease)은 대표적인 신경퇴행성 질환이며, 뇌 내 amyloid beta (Aβ) 축적에 의한 산화적 스트레스 및 염증반응은 대표적인 AD의 원인으로 알려져 있다. 본 연구에서는 kaempferol (K), kaempferol-3-O-glucoside (KG), quercetin (Q) 및 quercetin-3-β-ᴅ-glucoside (QG)와 같은 4가지 flavonoids의 C6 신경교세포에서 Aβ로 인한 신경독성으로부터의 보호 효능을 살펴보고자 하였다. C6 신경교세포에 Aβ를 처리하였을 때 세포 생존율이 감소한 반면, 4가지 flavonoids 중에서 Q와 QG의 처리 시 세포 생존율 증가를 통해 신경교세포 보호 효과를 확인하였다. 또한, Aβ를 처리한 control군의 경우 reactive oxygen species (ROS) 생성을 유도한 반면, flavonoids의 처리 시 ROS 생성이 감소하였다. 특히 Aβ를 처리한 control군은 133.39%의 ROS 생성을 나타내었으며, 1 μM의 KG와 QG를 각각 처리시 107.44, 113.10%의 수치를 나타내어 ROS 생성 감소를 확인하였다. Flavonoids의 Aβ에 대한 신경교세포 보호 기전을 확인하기 위해 염증 관련 단백질 발현을 측정하였다. Aβ로 신경독성이 유도된 control군은 염증 관련 단백질 발현이 증가하였다. 그러나, flavonoids를 처리한 군의 경우 염증 매개 인자인 inducible nitric oxide synthase, cyclooxygenase-2 and interleukin-1β의 발현 감소를 확인하였다. 특히, KG와 QG를 처리한 군은 aglycone 형태인 K와 Q를 처리한 군에 비해 효과적으로 염증 매개 인자 발현을 감소시켰다. 본 연구는 flavonoids의 일종인 K, Q와 그 배당체인 KG, QG의 Aβ로 신경독성이 유도된 신경교세포에서 산화적 스트레스 및 염증반응 조절을 통한 보호 효과를 나타냄을 알 수 있었으며, 이들 생리활성성분은 AD 예방 및 치료 소재로써의 가능성이 있을 것으로 사료된다.

• BMB Reports
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• 제52권7호
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• pp.439-444
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• 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.

• Nutrition Research and Practice
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• 제14권6호
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• pp.593-605
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• 2020

BACKGROUND/OBJECTIVES: Alzheimer's disease is common age-related neurodegenerative condition characterized by amyloid beta (Aβ) accumulation that leads cognitive impairment. In the present study, we investigated the protective effect of paeoniflorin (PF) against Aβ-induced neuroinflammation and the underlying mechanism in C6 glial cells. MATERIALS/METHODS: C6 glial cells were treated with PF and Aβ_25-35, and cell viability, nitric oxide (NO) production, and pro-inflammatory cytokine release were measured. Furthermore, the mechanism underlying the effect of PF on inflammatory responses and Aβ degradation was determined by Western blot. RESULTS: Aβ_25-35 significantly reduced cell viability, but this reduction was prevented by the pretreatment with PF. In addition, PF significantly inhibited Aβ_25-35-induced NO production in C6 glial cells. The secretion of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha was also significantly reduced by PF. Further mechanistic studies indicated that PF suppressed the production of these pro-inflammatory cytokines by regulating the nuclear factor-kappa B (NF-κB) pathway. The protein levels of inducible NO synthase and cyclooxygenase-2 were downregulated and phosphorylation of NF-κB was blocked by PF. However, PF elevated the protein expression of inhibitor kappa B-alpha and those of Aβ degrading enzymes, insulin degrading enzyme and neprilysin. CONCLUSIONS: These findings indicate that PF exerts protective effects against Aβ-mediated neuroinflammation by inhibiting NF-κB signaling, and these effects were associated with the enhanced activity of Aβ degradation enzymes.