채취시기별 보검선인장 줄기의 항산화, 항당뇨 및 항알츠하이머 활성평가

정윤숙 ( Yun Sook Jeong ),황병순 ( Byung Soon Hwang ),조수묵 ( Soo-muk Cho ),황경아 ( Kyung-a Hwang ),황인국 ( In Guk Hwang ) 한국식품영양학회 2017 韓國食品營養學會誌 Vol.30 No.6

In this study, we assessed antioxidant, anti-diabetic, and anti-Alzheimer activities of Opuntia ficus-indica var. saboten (OFI) at harvest time. OFIs were cultivated December 2015~November 2016 in Jeju island. The 70% ethanol extracts of OFI were used to investigate total polyphenol and flavonoid contents, antioxidant(DPPH and ABTS radical scavenging assay), anti-diabetic(yeast α-glucosidase and rat α-glucosidase inhibition assay), and anti-Alzheimer(Acetylcholinesterase and butyrylcholinesterase inhibition assay) activities. Total polyphenol and flavonoid contents of OFIs were 17.40~23.11 μg garlic acid/mg Ex and 2.17~6.22 ug (+)-catechine/mg Ex, respectively. DPPH and ABTS radical scavenging activity of OFIs were 131.98~184.90 mg ascorbic acid(AA) eq/100 g and 63.60~101.83 mg AA eq/100 g, respectively. In the anti-diabetic and anti-Alzheimer activities, 70% ethanol extracts of OFI exhibited moderate inhibition activity, compared to control (acarbose and beberine). Total polyphenol and flavonoid contents, antioxidant, anti-diabetic, and anti-Alzheimer activities were no significant differences by season, respectively. Therefore, information on comparative biological evaluations of OFI may be a beneficial in exploring functional food and drug development.

Korean traditional herbal formula Soshiho-tang attenuates memory impairment and neuronal damage in mice with amyloid-b eta-induce d Alzheimer’s disease

손은진,Yu Jin Kim,정수진 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.3

Background: Soshiho-tang (SST), also known as Xiaochaihu-tang in China and Sho-saiko-to in Japan, is an Oriental herbal formula traditionally used to treat febrile diseases. Recently, several in vitro and in vivo studies have reported the anti-cancer, anti-liver disease, and anti-inflammatory activities of SST. However, there is little evidence of its effects on neurological diseases. We previously reported the inhibitory effects of SST on in vitro acetylcholinesterase (AChE) activation and amyloid-β (Aβ) aggregation, which are crucial hallmarks of Alzheimer's disease (AD). In the present study, we report that SST has preventive effects on memory impairment and neuronal cell changes in an Aβ-induced AD-like mouse model. Methods: Male mice underwent injection of Aβ aggregates and administered SST (500, 1,000, or 2,000 mg/kg/day) for 20 days. Behavioral tests (passive avoidance task [PAT] and Morris water maze [MWM] test) were conducted. Lastly, brain sections were obtained from sacrificed mice for quantitative analysis. Results: Intracerebroventricular (ICV) injection of Aβ aggregates significantly decreased the latency time in the PAT and MWM test compared to normal control. In contrast, SST administration markedly reversed the latency caused by Aβ injection. Additionally, our data revealed that SST-mediated improvements in memory impairment are related to its neuroprotective and anti-neuroinflammatory effects. On histological analysis, SST treatment protected neuronal loss and damage as well as microglial activation, and ameliorated amount of Aβ in brain of mouse model of AD. Conclusion: Our findings suggest that SST may be a promising candidate for the development of novel drugs for AD.

Involvement of inflammation in Alzheimen`s disease pathogenesis and therapeutie potential of anti-inflammatory agents

( Sina Shadfar ),( Chul Ju Hwang ),( Mi Sun Lim ),( Dong Young Choi ),( Jin Tae Hong ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-

Alzheimer``s disease (AD) is the most common form of dementia. It is characterized by beta-amyloid (A~) peptide fibrils, which are extracellular depositions of a specific protein, and is accompanied by extensive neu-roinflammation. Various studies have demonstrated risk factors that can affect AD pathogenesis, and they include accumulation of Aβ, hyperphosphorylation of tau protein, and neuroinflammation. Among these detrimental factors, neuroinflammation has been highlighted by epidemiologic studies suggesting that use of anti-inflammatory drugs could significantly reduce the incidence of AD. Evidence suggests that astrocytes, microglia, and infiltrating immune cells from periphery might contribute to or modify the process of neuroinflammation and neurodegeneration in AD brains. In addition, recent data indicate that micro-RNAs may affect neuroinflammatory responses in the brain. This article focuses on supportive evidence that neuroinflammation plays a critical role in AD development. In addition, we depict putative therapeutic capacity of anti-inflammatory drugs for AD prevention or treatment. We also discuss pathogenic mechanisms by which astrocytes, microglia, T cells and microRNA participate in AD and the neuroprotective mechanisms of anti-inflammatory drugs.

알쯔하이머병 환자 혈청에서의 베타 아밀로이드 단백질에 대한 특이 항체량 측정 : 알쯔하이머병의 생화학적 진단지표 개발 Development of Biomarker for Alzheimer's Disease Diagnosis

소정온,허지연,심혜진,김종원,나덕렬,이필휴,정선주,박문호,주인수,송미숙,김영호,묵인희 대한치매학회 2004 Dementia and Neurocognitive Disorders Vol.3 No.1

Background:Alzheimer's disease (Ad) is a neurodegenerative disorder that is rapidly increasing with the aging society, requiring a need for early diagnosis and prevention. However, diagnosis on AD has only been possible through limited methods such as neuropsychological examination or MRI. AD is characterized by deposition of senile plaques and neurofibrillary tangles in the brain. Aβ peptide in senile plaques seems to play a central role in the neuropathology of AD. Several biochemical markers for AD are available, including reduced Aβ protein, a change in ratio between Aβ40 and 42 and increased level of tau protein in the cerebrospinal fluid (CSF). Methods:This study analyzes anti-Aβ antibody from serums of AD patients using the ELISA. The levels of anti-Aβ antibody from patients with idiopathic Parkinson's disease or stroke and from normal control were compared to that of AD patients. Results:Our results showed a significantly lower anti-Aβ antibody level in AD compared to those with other neurological diseases or control. Conclusions:These data showed that the anti-Aβ antibody level in the serum may be used to diagnose the presence of AD.

Inhibitory evaluation of oligonol on a-glucosidase, protein tyrosine phosphatase 1B, cholinesterase, and b-secretase 1 related to diabetes and Alzheimer’s disease

Jae Sue CHOI,Hyun Ah Jung,Himanshu Kumar Bhakta,Hajime Fujii,민병선,Chan Hum Park,Takako Yokozawa 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.3

Oligonol is a low-molecular-weight form of polyphenol that is derived from lychee fruit extract and contains catechin-type monomers and oligomers of proanthocyanidins. This study investigates the anti-diabetic activities of oligonol via a-glucosidase and human recombinant protein tyrosine phosphatase 1B (PTP1B) assays, as well as its anti-Alzheimer activities by evaluating the ability of this compound to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and b-site amyloid precursor protein cleaving enzyme 1 (BACE1). Oligonol exhibited potent concentration-dependent anti-diabetic activities by inhibiting a-glucosidase and PTP1B with IC50 values of 23.14 lg/mL and 1.02 lg/mL, respectively. Moreover, a kinetics study revealed that oligonol inhibited a-glucosidase (Ki = 22.36) and PTP1B (Ki = 8.51) with characteristics typical of a mixed inhibitor. Oligonol also displayed potent concentration-dependent inhibitory activity against AChE and BChE with IC50 values of 4.34 lg/mL and 2.07 lg/mL, respectively. However, oligonol exhibited only marginal concentrationdependent BACE1 inhibitory activity with an IC50 value of 130.45 lg/mL. A kinetics study revealed mixed-type inhibition against AChE (Ki = 4.65) and BACE1 (Ki = 58.80), and noncompetitive-type inhibition against BChE (Ki = 9.80). Furthermore, oligonol exhibited dosedependent inhibitory activity against peroxynitrite (ONOO-)-mediated protein tyrosine nitration. These results indicate that oligonol has strong preventative potential in diabetes mellitus and in Alzheimer’s disease.

알쯔하이머 병의 약물치료

최웅 충북대학교 의과대학 충북대학교 의학연구소 1999 忠北醫大學術誌 Vol.9 No.1

알쯔하이머 병(Alzheimer's disease, AD)은 치매의 가장 흔한 원인이며 60세 이상의 노령인구가 점점 증가하는 21세기에 들어서면 가장 큰 사회복지문제로 대두될 가능성이 크다. AD의 병태생리에 대해서는 분자생물학 및 세포생물학적 방법론을 이용하여 최근에 많은 연구가 진행되고 있으며, 여기에서 얻어진 지식을 바탕으로 AD의 예방, 조기진단 및 치료에 이용하려는 시도들이 이루어지고 있다. 약물로서 AD를 예방 또는 치료하고자 하는 노력은 (1) cholinomimetic drug (2) 항산화제(antioxidants) (3) 항염증약물 (4) estrogen (5) anti-amyloid 약물 등으로 분류될 수 있으며, 이 중에서 현재 시판중인 약물들은 아직까지는 증상이 발현된 AD환자를 대상으로 하는 것이므로 최소한 임상증상의 개선을 평가하기 위해서는 mild-to-moderate AD에서만 사용이 가능하지만, 여러 가지 노력에 의하여 효능이 우수하고 독성이 적은 AD의 예방 및 치료약물이 앞으로 개발될 것으로 예상된다. Alzheimer's disease (AD) is the most common cause of dementia. AD is expected to be one of the biggest social and welfare problems in 21st century, when the size of the population over 60-year old is steadily growing. Using various methods of molecular and cellular biology, there has been much advancement in the research of pathogenesis of AD. Based on these knowledges, they are trying to develop methods for the prevention, the early diagnosis and the treatment of AD. Current pharmacological intervention for AD can be classified into groups such as (1) cholinomimetic drugs, (2) antioxidants, (3) anti-inflammatory drugs, (4) estrogen and (5) anti-amyloid drugs. Some of currently marketed drugs are targeted for clinically symptomatic AD. To evaluate the improvement after treatment, these drugs can be prescribed only to the mild-to-moderate AD patients. It is expected that many drugs with a better efficacy and lesser side effects shall be developed by these approaches.

The drinking effects of hydrogen water on alzheimer’s patient through oxidative stress and immune redox balance mechanism

Johny Bajgai,Kyu-Jae Lee 한국물학회 2017 한국물학회지 Vol.6 No.1

Hydrogen water (HW) produced by electrolysis of water has characteristics of extremely low oxidation-reduction potential (ORP) value and high dissolved hydrogen (DH). It has been proved to have various beneficial effects including antioxidant and anti-inflammatory effects; however, HW effect on Alzheimer's disease (AD), type of dementia that is associated with cognitive impairment and memory loss, is poorly documented. In the present study, we investigated the drinking effects of hydrogen water on alzheimer’s patient for prevention of AD through oxidative stress and immuno redox mechanism. Alzheimer’s patients were administered with HW and purified water (PW) for 6 months. Further, we evaluated the drinking effect of hydrogen water on the cognitive impairment of AD patients by checking the serum concentration of AD biomarkers (Amyloid ; (A ) 40, 42 and tau), pro-β β inflammatory (IL-1β, IL-13), anti-inflammatory (IL-6, IL-10), macrophage activated Th1 (IL-2, IFN-γ, TNF-α, and IL-12p70), Th2 (IL-4, IL-5,) cytokines, reactive oxygen species (ROS) and nitric oxide (NO) level. We found that HW treatment significantly decrease the serum level of AD biomarker (Aβ- 40) during 6 month of treatment. In parallel, pro and anti-inflammatory cytokines were significantly inhibited in experimental group than control group. In line, macrophage activated TH1 cytokine, Th2 cytokines and ROS level were significantly decreased in HW than PW group. Likewise, HW treatment shows reduction in nitric oxide level than control group. Overall our clinical results strongly recommended that drinking hydrogen water might be a promising preventative approach for age-related neurodegenerative disease like AD and have an enormous impact on future healthcare for the elderly patients. This is the first note on the clinical application of drinking HW on the serum of AD patients.

Safety and Efficacy of Anti-dementia Agents in the Extremely Elderly Patients with Dementia

임은예,양동원,김정석,조아현 대한의학회 2018 Journal of Korean medical science Vol.33 No.19

Background: There are debates on representation and generalizability of previous randomized controlled trials about anti-dementia agents in the oldest old population. In this context, we aimed to investigate the efficacy and safety of anti-dementia agents in the very elderly patients with dementia. Methods: We conducted a retrospective study of patients with dementia 1) who were 85 years or older, 2) got started anti-dementia agents, and 3) went through follow-up evaluation about one year thereafter. As a control, patients with dementia who were less than 85 years old with similar inclusion criteria were randomly selected during the same period. The adverse drug effects and discontinuation rates were investigated with self-reported complaint after starting or increasing anti-dementia drugs. For efficacy outcome, we also analyzed the change in neuropsychological results during follow-up period. Results: A total of 77 dementia patients who were at least 85 years were enrolled. As a control group, 78 patients with dementia who were younger than 85 was analyzed. The adverse drug effects were observed in 26 (33.3%) patients in the younger old and in 26 (33.8%) in the oldest old (P = 0.095). Twenty-one patients (26.9%) in the younger old group and 13 patients (16.9%) in the oldest old group discontinued their medication (P = 0.131). There were no differences between the two groups about changes of Mini-Mental State Examination and Instrumental Activity of Daily Living scores over time. Conclusion: The use of anti-dementia agents in the oldest old dementia patients may be safe and effective as the younger old dementia patients.

트레드밀 운동이 mutant (N141I) presenilin-2 유전자를 이식한 알츠하이머질환 모델 생쥐 뇌의 Aβ-42, cytochrome c, SOD-1, 2와 Sirt-3 단백질 발현에 미치는 영향

Jung-Hoon Koo(구정훈),Hyun-Sub Eum(엄현섭),Eun-Bum Kang(강은범),In-Su Kwon(권인수),Dong-Cheol Yeom(염동철),Gil-Young An(안길영),Yoo-Sung Oh(오유성),Young-Soo Baik(백영수),In-Ho Cho(조인호),Joon-Yong Cho(조준용) 한국생명과학회 2010 생명과학회지 Vol.20 No.3

본 연구의 목적은 PS-2 (N141I) 알츠하이머 형질전환 모델 생쥐를 대상으로 트레드밀 운동이 뇌의 세포질과 미토콘드리아의 Aβ-42, cytochrome c, SOD-1, 2 and Sirt-3 단백질 발현에 미치는 효과를 알아보는데 있다. 우선 알츠하이머 형질전환 생쥐를 Non-Tg-sedentary (n=5), Non-Tg-treadmill exercise (n=5) 집단과 Tg-sedentary (n=5), Tg-treadmill exercise (n=5) 집단으로 구분하고 트레드밀 운동을 통한 신경보호 효과를 검증하기 위해 Tg와 Non-Tg집단에 12주간 트레드밀 운동을 수행한 후 인지능력을 살펴보고 뇌의 세포질과 미토콘드리아의 Aβ-42, cytochrome c, anti-oxidant enzymes (SOD-1, SOD-2)와 Sirt-3 단백질을 분석하였다. 먼저 트레드밀운동은 Tg 집단에서 인지능력의 개선을 나타냈으며 미토콘드리아의 Aβ-42와 세포질의 cytochrome c 단백질의 감소와 항산화 효소인 SOD-1, SOD-2를 유의하게 증가시켰다. 게다가 트레드밀 운동은 모든 집단에서 Sirt-3 단백질의 발현을 증가시켰다. 따라서 트레드밀 운동은 인지능력의 향상과 세포 내 스트레스를 유발하는 Aβ-42를 억제시켜 알츠하이머 질환을 개선시킬 수 있는 효과적인 방법이라고 생각된다. The purpose of this study was to investigate the effects of treadmill exercise on Aβ-42, cytochrome c, SOD-1, 2 and Sirt-3 protein expressions in brain cytosol and mitochondria in mutant (N141I) presenilin-2 transgenic mice with Alzheimer's disease (AD). The mice were divided into four groups (Non-Tg-sedentary, n=5; Non-Tg treadmill exercise, n=5; Tg-sedentary, n=5; Tg treadmill exercise, n=5). To evaluate the neuroprotective effect of treadmill exercise, Non-Tg and Tg mice were subjected to exercise training on a treadmill for 12 wk, after which their brain cytosol and mitochondria were evaluated to determine whether any changes in the cognitive performance, Aβ-42 protein, cytochrome c protein, anti-oxidant enzymes (SOD-1, SOD-2) and Sirt-3 protein had occurred. The results indicated that treadmill exercise resulted in amelioration in cognitive deficits of Tg mice. In addition, the expressions of mitochondrial Aβ-42 and cytosolic cytochrome c protein were decreased in the brains of Tg mice after treadmill exercise, whereas antioxidant enzymes, SOD-1 and SOD-2 were significantly increased in response to treadmill exercise. Furthermore, treadmill exercise significantly increased the expression of Sirt-3 protein in Non-Tg and Tg mice. Taken together, these results suggest that treadmill exercise is a simple behavioral intervention which can sufficiently improve cognitive performance and inhibit Aβ-induced oxidative stress in AD.

CT99 발현 PC12 세포주에서 가감고본환의 신경보호 및 항치매 효과

안대광,이소연,윤현덕,신오철,박창국,박치상,Ahn, Dae-Gwang,Lee, So-Yeon,Yoon, Hyeon-Deok,Shin, Wo-Cheol,Park, Chang-Gook,Park, Chi-Sang 대한한의학방제학회 2005 大韓韓醫學方劑學會誌 Vol.13 No.1

Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the biggest problem in public health service. It has been widely believed that $A{\beta}$ peptide devided from APP causes apoptotic neurotoxicity in brain. However, recent evidence suggests that n99 may be an important factor causing neurotoxicity in AD. Mouse PC12 cells expressed with n99 exhibited remarkable apoptotic cell damage. We invesgated the protective effects of Gagamgobonhwan water extract(GKG). Findings from our experiments have shown that GKG inhibits the activities of CT99, which has neurotoxicities and apoptotic activities in cell line. In addition, treatment of GKG($75{\mu}g/ml$ 24 hours) partially prevented CT99-induced cytotoxicity in PC12 cells. As the result of this study, in GKG group the apoptosis in the nervous system was inhibited, the repair against the degerneration of PC12 cells by CT99 expression is promoted. Taken together, GKG exhibited inhibition of CT99-induced apoptotic cell death. GKG may be beneficial for the treatment of AD.