• 한국약용작물학회지
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• 제25권6호
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• pp.353-360
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• 2017

Background: A critical features of Alzheimer's disease (AD) is cognitive dysfunction, which partly arises from decreased in acetylcholine levels. AD afftected brains are characterized by extensive oxidative stress, which is thought to be primarily induced by the amyloid beta ($A{\beta}$) peptide. In a previous study, Cinnamomum loureiroi tincture inhibited acetylcholinesterase (AchE) activity. That study identified AChE inhibitor in the C. loureiroi extract. Furthermore, the C. loureiroi extract enhanced memory in a trimethyltin (TMT)-induced model of cognitive dysfunction, as assessed via two behavioral tests. Rosa laevigata extract protected against oxidative stress-induced cytotoxicity. Administrating R. laevigata extracts to mice significantly reversed $A{\beta}$-induced learning and memory impairment, as shown in behavioral tests. Methods and Results: We conducted behavioral to examine the synergistic effects of C. loureiroi and R. laevigata extracts in inhibiting AChE and counteracting TMT-induced learning and memory losses. We also performed biochemical assays. The biochemical results showed a relationship between increased oxidative stress and cholinergic neurons damage in TMT-treated mice. Conclusions: A diet containing C. loureiroi and R. laevigata extracts ameliorated learning and memory impairments in the Y-maze and passive avoidance tests, and exerted synergistic inhibitory effect against AChE and lipid peroxidation.

• 대한본초학회지
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• 제22권1호
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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.

• 한국식품영양학회지
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• 제27권4호
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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.

• Nutrition Research and Practice
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• 제17권2호
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• pp.371-385
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• 2023

BACKGROUND/OBJECTIVES: Soy isoflavone (SIF) and soy lecithin (SL) have beneficial effects on many chronic diseases, including neurodegenerative diseases. Regretfully, there is little evidence to show the combined effects of these soy extractives on the impairment of cognition and abnormal cerebral blood flow (CBF). This study examined the optimal combination dose of SIF + SL to provide evidence for improving CBF and protecting cerebrovascular endothelial cells. MATERIALS/METHODS: In vivo study, SIF50 + SL40, SIF50 + SL80 and SIF50 + SL160 groups were obtained. Morris water maze, laser speckle contrast imaging (LSCI), and hematoxylin-eosin staining were used to detect learning and memory impairment, CBF, and damage to the cerebrovascular tissue in rat. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the oxidized glutathione (GSSG) were detected. The anti-oxidative damage index of superoxide dismutase (SOD) and glutathione (GSH) in the serum of an animal model was also tested. In vitro study, an immortalized mouse brain endothelial cell line (bEND.3 cells) was used to confirm the cerebrovascular endothelial cell protection of SIF + SL. In this study, 50 µM of Gen were used, while the 25, 50, or 100 µM of SL for different incubation times were selected first. The intracellular levels of 8-OHdG, SOD, GSH, and GSSG were also detected in the cells. RESULTS: In vivo study, SIF + SL could increase the target crossing times significantly and shorten the total swimming distance of rats. The CBF in the rats of the SIF50 + SL40 group and SIF50 + SL160 group was enhanced. Pathological changes, such as attenuation of the endothelium in cerebral vessels were much less in the SIF50 + SL40 group and SIF50 + SL160 group. The 8-OHdG was reduced in the SIF50 + SL40 group. The GSSG showed a significant decrease in all SIF + SL pretreatment groups, but the GSH showed an opposite result. SOD was upregulated by SIF + SL pretreatment. Different combinations of Genistein (Gen)+SL, the secondary proof of health benefits found in vivo study, showed they have effective anti-oxidation and less side reaction on protecting cerebrovascular endothelial cell. SIF50 + SL40 in rats experiment and Gen50 + SL25 in cell test were the optimum joint doses on alleviating cognitive impairment and regulating CBF through protecting cerebrovascular tissue by its antioxidant activity. CONCLUSIONS: SIF+SL could significantly prevent cognitive defect induced by β-Amyloid through regulating CBF. This kind of effect might be attributed to its antioxidant activity on protecting cerebral vessels.

• Journal of Ginseng Research
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• 제45권4호
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• pp.473-481
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• 2021

Background: Mitochondrial dysfunction is one of the significant reasons for Alzheimer's disease (AD). Ginsenosides, natural molecules extracted from Panax ginseng, have been demonstrated to exert essential neuroprotective functions, which can ascribe to its anti-oxidative effect, enhancing central metabolism and improving mitochondrial function. However, a comprehensive analysis of cellular mitochondrial bioenergetics after ginsenoside treatment under Aβ-oxidative stress is missing. Methods: The antioxidant activities of ginsenoside Rb₁, Rd, Re, Rg₁ were compared by measuring the cell survival and reactive oxygen species (ROS) formation. Next, the protective effects of ginsenosides of mitochondrial bioenergetics were examined by measuring oxygen consumption rate (OCR) in PC12 cells under Aβ-oxidative stress with an extracellular flux analyzer. Meanwhile, mitochondrial membrane potential (MMP) and mitochondrial dynamics were evaluated by confocal laser scanning microscopy. Results: Ginsenoside Rg₁ possessed the strongest anti-oxidative property, and which therefore provided the best protective function to PC12 cells under the Aβ oxidative stress by increasing ATP production to 3 folds, spare capacity to 2 folds, maximal respiration to 2 folds and non-mitochondrial respiration to 1.5 folds, as compared to Aβ cell model. Furthermore, ginsenoside Rg1 enhanced MMP and mitochondrial interconnectivity, and simultaneously reduced mitochondrial circularity. Conclusion: In the present study, these results demonstrated that ginsenoside Rg₁ could be the best natural compound, as compared with other ginsenosides, by modulating the OCR of cultured PC12 cells during oxidative phosphorylation, in regulating MMP and in improving mitochondria dynamics under Aβ-induced oxidative stress.

• 한국식품과학회지
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• 제45권2호
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• pp.257-261
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• 2013

본 연구는 산화적 스트레스로부터 유도되는 신경세포 사멸을 보호할 수 있는 생리활성물질을 탐색하기 위하여 검정콩 껍질 추출물의 항산화 효과 및 PC12 신경세포 보호효과에 대하여 조사하였다. 다양한 용매에 의해 추출된 검정콩 껍질 추출물의 총 페놀화합물 함량을 측정한 결과 70% acetone 추출물이 다른 용매추출물에 비하여 가장 높은 총 페놀화합물 함량을 나타내었으며, 이를 기초로 70% acetone 추출물을 이용한 세포 내 항산화 활성도 높은 것으로 나타났다. 또한 PC12 신경세포 보호효과를 조사한 결과, 세포생존율과 세포막 손상 보호효과에서 70% acetone 추출물 처리구는 최대 $500{\mu}g/mL$까지 $H_2O_2$를 처리한 대조구에 비하여 농도 의존적으로 신경세포 보호효과가 나타남을 알 수 있었다. 동일 추출물을 활용한 in vivo 인지학습능력 평가에서도 대조구인 $A{\beta}$ ICV injection을 한 group과 비교하였을 때 전체적으로 추출물의 농도가 증가할수록 Y-maze test와 passive avoidance test에서 control구와 유사하거나 높은 인지 및 기억 능력 회복효과를 보여주었다. 본 연구결과를 종합해 보면 BSSCE는 항산화, 뇌 신경세포 보호효과 및 in vivo 인지 기억 회복능을 갖는 것으로 판단되며, 추후 검정콩 껍질에 존재하는 유효 생리활성물질을 확인함으로써 현대 사회의 가장 큰 질병 중 하나인 알츠하이머성 치매(AD)와 같은 퇴행성 뇌신경질환 예방에 유용한 소재가 될 것으로 판단된다.

• 한국식품과학회지
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• 제38권3호
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• pp.452-455
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• 2006

퇴행성뇌질환인 치매의 정확한 원인은 아직 불분명하나 빠른 뇌세포사멸이 주요한 원인으로 알려져 있다. 특히, 알츠하이머형 치매는 다량 생성되는 활성산소에 의한 뇌세포사멸이 주요원인인 것으로 입증되고 있다. 따라서 본 연구에서는 웅담활성성분인 UDCA의 세포보호 및 항산화효과로부터 알츠하이머형 치매와 같은 퇴행성 뇌질환억제 또는 치료물질로서의 가능성을 입증하고자 하였고 뇌의 대식세포인 소교세포(microglia)를 cell model로 하였다. MTT 실험결과 UDCA에 의한 세포보호효과는 $7.5\;{\mu}g/mL$ 주변 농도에서 관찰되었고 NO에 의한 세포손상 유도억제효과를 확인하였다(Fig. 2). 이와 같은 결과는 형광현미경하에서 보다 명확히 관찰되어(Fig. 3) 결국 UDCA에 의한 항세포사효과가 있음을 알 수 있었다. UDCA의 항산효과는 활성산소인 $H_2O_2$의 단백질 분해 저해능을 관찰하는 금속이온촉매 산화효과를 통해 확인하였다(Fig. 4). 즉, UDCA는 농도의존적으로$(1{\sim}100\;{\mu}g/mL)$ 단백질 분해억제능을 보였으며 $100\;{\mu}g/mL$ 이상의 농도에서 양성대조군인 ascorbic acid와 유사한 억제효과를 나타냈다. 이와 같은 UDCA의 항산화효과는 $10\;{\mu}g/mL$ 전후에서 관찰되어 세포보호효과를 나타내는 농도$(7.5\;{\mu}g/mL)$와 큰 차이가 없는 것으로 사료되었고 따라서 UDCA의 농도범주는 일괄적 적용이 가능할 것으로 판단된다. 결론적으로 웅담활성성분인 UDCA는 일반적으로 사용하여온 간질환 및 소화계질환의 보조요법제의 개념을 벗어나 항염 및 항산화효과에 잠재능을 가지며 나아가 뇌신경세포를 보호하고 세포사를 차단하여 알츠하이머와 같은 퇴행성뇌질환 조절 후보물질로 적용이 가능할 것으로 판단되나 보다 심도 있는 in vivo 및 임상적 차원의 연구가 요구된다.