• 대한본초학회지
• /
• 제34권4호
• /
• pp.9-18
• /
• 2019

Objectives : It has been known to be correlated between phlegm and dementia from the perspective of oriental medicine, but it is unexplored whether herbal medicines to treat phlegm have pharmacological actions on Alzheimer's disease (AD). The aim of this study was to evaluate and to compare effects of herbal medicines to treat phlegm against AD in vitro. Methods : We selected 11 herbal medicines which treat phlegm and obtained each extract by boiling in 10-fold distilled water for 2 h. And we performed the assay of acetylcholinesterase (AChE) inhibitory effects of 11 herbal extracts. Next, we evaluated neuroprotective effects of them against amyloid $beta_{25-35}$ ($A{\beta}_{25-35}$) plaque-induced toxicity in HT22 mouse hippocampal neuronal cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. To investigate whether they show the anti-inflammatory effects against lipopolysaccharide (LPS), we also measured the levels of nitric oxide (NO) in BV2 microglia cells using griess reagent assay. Results : We found that Gamiyeongsin-hwan (GYH) and Cheonghunhwadam-tang (CHT) exhibited remarkable AChE inhibitory effects. In HT22 cells, Arisaematis Rhizoma, Trichosanthis Semen and Fritillariae Thunbergii Bulbus suppressed $A{\beta}_{25-35}$ plaque-induced neuronal cell death. In BV2 cells, Cheongung-hwan significantly inhibited the increase of NO contents induced by LPS and GYH and CHT showed a tendency to inhibit LPS-induced NO generation. Conclusions : These results suggest that several herbal medicines to treat phlegm showed the significant effects on AChE inhibition, neuroprotection against $A{\beta}_{25-35}$ plaque-induced toxicity, and inhibition of NO generation. Therefore, we demonstrate the possibility that herbal medicines with treating phlegm has effects against AD.

• Journal of Applied Biological Chemistry
• /
• 제64권3호
• /
• pp.299-307
• /
• 2021

뇌 내 amyloid beta (Aβ) 축적으로 인한 신경독성은 산화적 스트레스를 야기하여 알츠하이머 질환(Alzheimer's disease, AD)을 유도하는 것으로 알려져 있다. 본 연구는 여주(Momordica charantia L.)의 활성분획물인 butanol (BuOH) 분획물의 Aβ_25-35 유도 AD 동물모델에서 인지능 개선 효과에 대해 연구하였다. T-미로 실험 및 물체인지실험을 통해서 여주 BuOH 분획물 100 및 200 mg/kg/day 농도 투여군은 AD를 유도한 control군에 비해 유의적으로 새로운 경로와 물체를 탐색하는 비율이 감소되어 공간인지 및 물체인지능력 개선 효과를 확인하였다. 수중미로실험을 통해 학습·기억력에 미치는 효과를 측정한 결과, 여주 BuOH 분획물 투여군은 훈련을 반복할수록 숨겨진 도피대를 찾아가는 시간이 감소함을 통해 학습·기억력 개선 효과를 나타내었다. 여주 BuOH 분획물이 산화적 스트레스 개선 효과에 미치는 효과를 확인하기 위해 뇌, 간, 신장 조직에서 지질과 산화 함량 및 nitric oxideNO 생성량을 측정하였다. 여주 BuOH 분획물을 처리한 군은 Aβ_25-35를 주입한 control군에 비해 유의적으로 뇌, 간, 신장 조직에서 지질과산화 함량 및 NO 생성량이 감소되어 산화적 스트레스 개선 효과를 확인하였다. 따라서 본 연구는 여주 BuOH 분획물이 Aβ_25-35 유도 AD 동물모델에서 산화적 스트레스 개선을 통해 인지능력 개선 효과를 나타냄을 확인하였으며, 이에 따라 여주는 AD 예방 및 개선용 소재로써의 가능성이 있는 것으로 사료된다.

• 한국응용과학기술학회지
• /
• 제35권2호
• /
• pp.389-398
• /
• 2018

본 연구는 노루궁뎅이버섯 균사체로 발효시킨 엄나무 추출물의 항산화 및 항아밀로이드 활성을 알아보고자 하였다. 항산화 활성은 2,2-diphenyl-1-picrylhydrazyl(DPPH) radical, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) radical 소거 측정법을 사용하여 관찰하였다. 엄나무추출물(KP), 노루궁뎅이버섯 균사체 추출물(HE), 엄나무 발효물(KP-HE)에서 모두 라디칼 소거활성이 관찰되었다. 그러나 KP-HE가 KP와 HE에 비해서 더 높은 소거 활성을 갖는 것으로 관찰되었다. KP-HE는 peroxyl radical에 의한 DNA의 산화적 손상을 억제하였다. 알츠하이머병 (Alzheimer's disease: AD)과 관련 있는 $A{\beta}_{1-42}$의 응집에 KP, HE, KP-HE가 어떤 영향을 미치는 지를 알아보았다. KP와 HE는 $A{\beta}_{1-42}$의 응집에 거의 영향을 미치지 않았고 KP-HE는 $A{\beta}_{1-42}$의 응집을 효과적으로 억제하였다. 또한 $A{\beta}_{1-42}$에 의한 신경세포 사멸에 엄나무 발효물을 $300{\mu}g/mL$ 농도로 전 처리한 세포생존율은 20.3% 높게 증가되었다. 또한 엄나무 발효물을 $50{\mu}g/mL$ 농도로 처리했을 경우 세포 내 ROS의 축적이 유의적으로 감소되었다. 결론적으로 본 연구에서 관찰된 결과들을 통해 엄나무 발효물은 항산화 및 항아밀로이드 활성을 가지는 것으로 확인되었다. 따라서 엄나무 발효물은 알츠하이머병과 같은 퇴행성 뇌질환을 예방할 수 있는 식품소재로 이용될 수 있을 것으로 사료된다.

• 동의신경정신과학회지
• /
• 제11권2호
• /
• pp.23-42
• /
• 2000

Alzheimer's disease(AD) is progressive neurodegenerative disease, which is pathologically characterized by neuritic plaques and neurofibrillary tangles associated with the acetylcholinesterase, apolipoprotein E and butylcholinesterase, and by mutations in the presenilin genes PSI and PS2, and amyloid precursor proteins (APP) overexpression. The present research is to examine the inhibition effect of YJJHT on PS-1, PS-2 and APP overexpression by detected to Western blotting. To verify the EFFects of YJJHT on cognitive deficits further, we tested it on the scopolamine-induced amnesia model of the mice using the Morris water maze tests. and there was ameliorative effects of memory impairment s a protection to scopolamine. YJJHT only partially blocked the increase in blood serum level of acetylcholinesterase and Uric acid induced by scopolamine. whereas blood glucose level was shown to attenuate the amnesia induced by scopolamine and inreased extracellular serum level compared with only scopolamine injection. In conclusion, studies of YJJHT that has been know as anti-choline and inhibition ablilities of APP overexpression, this could also be used further as a important research data for a preventive and promising symptomatic treatment for Alzheimer's disease.

• Journal of Ginseng Research
• /
• 제45권5호
• /
• pp.599-609
• /
• 2021

Ginseng has long been considered as an herbal medicine. Recent data suggest that ginseng has antiinflammatory properties and can improve learning- and memory-related function in the central nervous system (CNS) following the development of CNS neuroinflammatory diseases such as Alzheimer's disease, cerebral ischemia, and other neurological disorders. In this review, we discuss the role of ginseng in the neurovascular unit, which is composed of endothelial cells surrounded by astrocytes, pericytes, microglia, neural stem cells, oligodendrocytes, and neurons, especially their blood-brain barrier maintenance, anti-inflammatory effects and regenerative functions. In addition, cell-cell communication enhanced by ginseng may be attributed to regeneration via induction of neurogenesis and angiogenesis in CNS diseases. Thus, ginseng may have therapeutic potential to exert cognitive improvement in neuroinflammatory diseases such as stroke, traumatic brain injury, multiple sclerosis, Parkinson's disease, and Alzheimer's disease.

• Fisheries and Aquatic Sciences
• /
• 제21권12호
• /
• pp.38.1-38.9
• /
• 2018

Alzheimer's disease (AD) is a disturbing and advanced neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta ($A{\beta}$) and the hyperphosphorylation of tau proteins in the brain. The deposition of $A{\beta}$ aggregates triggers synaptic dysfunction, and neurodegeneration, which lead to cognitive disorders. Here, we found that FF isolated from an eatable perennial brown seaweed E.bicyclis protect against $A{\beta}$-induced neurotoxicity in neuroblastoma cells stably transfected with two amyloid precursor protein (APP) constructs: the APP695 cDNA (SH-SY5Y-APP695swe). The FF demonstrated strong inhibitory activity for ${\beta}$-secretase ($IC_{50}$ $16.1{\mu}M$) and its inhibition pattern was investigated using Lineweaver-Burk and Dixon plots, and found to be non-competitive. Then, we tested whether FF could inhibit production of $A{\beta}$ in SH-SY5Y-APP695swe. FF inhibited the production of $A{\beta}$ and soluble-APP, residue of APP from cleaved APP by ${\beta}$-secretase. Our data show that FF can inhibit the production of $A{\beta}$ and soluble-$APP{\beta}$ via inhibition of ${\beta}$-secretase activity. Taken together these results suggest that FF may be worthy of future study as an anti-AD treatment.

• Journal of Ginseng Research
• /
• 제40권1호
• /
• pp.9-17
• /
• 2016

Background: Alzheimer's disease (AD) is a progressive brain disease, for which there is no effective drug therapy at present. Ginsenoside Rg1 (G-Rg1) and G-Rg2 have been reported to alleviate memory deterioration. However, the mechanism of their anti-AD effect has not yet been clearly elucidated. Methods: Ultra performance liquid chromatography tandem MS (UPLC/MS)-based metabolomics was used to identify metabolites that are differentially expressed in the brains of AD mice with or without ginsenoside treatment. The cognitive function of mice and pathological changes in the brain were also assessed using the Morris water maze (MWM) and immunohistochemistry, respectively. Results: The impaired cognitive function and increased hippocampal $A{\beta}$ deposition in AD mice were ameliorated by G-Rg1 and G-Rg2. In addition, a total of 11 potential biomarkers that are associated with the metabolism of lysophosphatidylcholines (LPCs), hypoxanthine, and sphingolipids were identified in the brains of AD mice and their levels were partly restored after treatment with G-Rg1 and G-Rg2. G-Rg1 and G-Rg2 treatment influenced the levels of hypoxanthine, dihydrosphingosine, hexadecasphinganine, LPC C 16:0, and LPC C 18:0 in AD mice. Additionally, G-Rg1 treatment also influenced the levels of phytosphingosine, LPC C 13:0, LPC C 15:0, LPC C 18:1, and LPC C 18:3 in AD mice. Conclusion: These results indicate that the improvements in cognitive function and morphological changes produced by G-Rg1 and G-Rg2 treatment are caused by regulation of related brain metabolic pathways. This will extend our understanding of the mechanisms involved in the effects of G-Rg1 and G-Rg2 on AD.

• 동의생리병리학회지
• /
• 제19권1호
• /
• pp.242-245
• /
• 2005

The most common feature of neurodegenerative disease (i.e. Alzheimer's disease, AD) is the increased number of activated microglial cells nearby the pathogenic area of the brain, such as amyloid plaque in AD. An abnormality of protein regulation and an imbalance of clearance against ${\beta}-amyloid\;(A{\beta})$ produced amyloid precursor protein (APP) can turn microglia into the activated feature out of the ramified resting phase. We examined the possibility that ginsenoside Rb1 could attenuate the microglial activation induced by massive $A{\beta}$ that has known to induce a chronic inflammation, which is a major cause of AD by damaging neuronal cells (i.e. apoptosis or necrosis). Aggregated $A{\beta}42\;(5\;{\mu}M)$ peptide was used with lipopolysaccharide (LPS) ($10\;{\mu}g$) for a comparative control up to 48hours. We found that Rb1 reduced the production of nitric oxide as well as proinflammatory cytokines, such as $IL-1{\beta}$ and $TNF-{\alpha}$.

• 동의신경정신과학회지
• /
• 제11권1호
• /
• pp.19-36
• /
• 2000

Alzheimer's disease (AD) is progressive neurodegenerative disease, which is pathologically characterized by neuritic plaques and neurofibrillary tangles associated with the acetylcholinesterase, apolipoprotein E and butylcholinesterase, and by mutations in the presenilin genes PS1 and PS2, and amyloid precursor proteins (APPs) overexpression. The present research is to examine the inhibition effect of KBT on PS1, PS2 and APPs overexpression by detected to Western blotting. To verify the Effects of KBT on cognitive deficits further, we tested it on the scopolamine (1 mg/kg)-induced amnesia model of the mice using the Morris water maze tests, and there was ameliorative effects of memory impairment as a protection to scopolamine. KBT only partially blocked the increase in blood serum level of acetylcholinesterase and Uric acid induced by scopolamine, whereas blood glucose level was shown to attenuate the amnesia induced by scopolamine and inreased extracellular serum level compared with only scopolamine injection. In conclusion, studies of KBT that has been know as anti-choline and inhibition ablilities of APPs overexpression, this could also be used further as a important research data for a preventive and promising symptomatic treatment for Alzheimer's disease.

• 대한한방내과학회지
• /
• 제27권3호
• /
• pp.603-616
• /
• 2006

The water extract of Gamiyaengshinhwan (GYH), has been used in vitro tests for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with CT105-related dementias and Alzheimer's disease(AD). CT105 derived from proteolytic processing of the $\beta$-amyloid precursor protein (APP), including the amyloid-$\beta$ peptide ($A{\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. We determined that transfected overexpressing APP695 and $A{\beta}$ CT105 have a profound attenuation in the Increase in CT105 expressing neuro2A cells from GYH. Experimental evidence indicates that GYH protects against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing CT105-associated neuronal degeneration, we demonstrated that GYH inhibits formation of amyloid-$\beta$ fragment ($A{\beta}$ CT105). which are the characteristic, and possibly causative, features of AD. The decreased CT105 $A{\beta}$ in the presence of GYH was observed in the conditioned medium of this CT105-secreting cell line under in vitro. In the cells, GYH significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of Bax, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct CT05 toxicity and the apoptosis initiated by the mitochondria. Multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of CT105 aggregation, underlie the neuroprotective effects of GYH.