• 대한한방내과학회지
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• 제41권3호
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• pp.326-338
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• 2020

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease that causes disorientation, mood swings, problems with language, and difficulty remembering recent events. Acetylcholinesterase inhibitors (AchEIs) and memantine have been used to slow the course of the disease, but they can neither modify its progression nor prevent disease onset. Previous studies have suggested that Kami-guibi-tang (KGT) could be beneficial for supporting cognitive function in AD patients, but few clinical trials have been published. This pilot study aimed to evaluate the effect of KGT in improving cognitive function in AD patients. Methods: The study will be a randomized, placebo-controlled, double-blind, single-center trial conducted using subjects diagnosed with mild AD by neurologists. Study subjects will be randomly assigned to either a treatment or control group. The treatment group will receive KGT granules for 24 weeks, while the control group will receive placebo granules. AchEI administration will be maintained in both groups during the entirety of the study. Subjects will be assessed using the following exams: the Seoul Neuropsychologic Screening Battery (SNSB) for cognitive function; brain magnetic resonance imaging (MRI) for brain metabolite, neurotransmitter, and cerebral blood flow (CBF) measurements; the Korean version of Quality of Life-Alzheimer's Disease (KQol-AD) for quality of life; the Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) for neurobehavioral symptoms; blood tests for amyloid and tau proteins and general blood parameters; and electrocardiography (ECG) before and after taking the medication. Discussion: Our findings will provide insight into the feasibility of large-scale trials to consolidate evidence for the efficacy of KGT for dementia treatment. Registration ID in CRIS: KCT0002904 (Clinical Research Information Service of the Republic of Korea).

• 대한한의학회지
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• 제25권4호
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• pp.1-7
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• 2004

Objective : This study was designed to examine the effects of orally administered Prunus persica water extract (PPE), which is used as herbal medicine, for treatment of Yu Xue (stasis of blood) and tacrine on the basal concentration of extracellular acetylcholine in the hippocampus of rats. Methods: To investigate the effects of PPE and tacrine on concentration of extracellular acetylcholine in the hippocampus of rats, the microdialysis technique, under the same experimental conditions, was used. And we used male Wistar rats which were 7 weeks of age and 210-290 g. PPE was extracted with boiling water, and the rats were anesthetized with pentobarbital Na. Their skulls were exposed and a hole was drilled for implantation of a microdialysis probe. In order to increase the recovery of acetylcholine, a probe with a long membrane was used. One day after surgery, the microdialysis probe was perfused with Ringer's solution at a flow rate of 1.5 l/min. The acetylcholine concentration in dialysis samples was measured by high-performance liquid chromatography (HPLC) with electrochemical detection. AChE activity was measured using the radiometric method, as described by Sherman. Results : The comparative effects of PPE and tacrine on hippocampal extracellular acetylcholine concentration was that these cholinesterase inhibitors produced dose-dependent increases in the extracellular acetylcholine concentration. And the effect of PPE and tacrine on rat brain AChE activity was that PPE produced maximal inhibition at 1 h after administration, when AChE activity was 44% of the intact level. AChE activity gradually recovered thereafter, and reached 78% of the intact level at 12 h after administration. Conclusion : In this study, PPE has a potent activity and a long-lasting effect on the central cholinergic system, in terms of the basal concentration of extracellular acetylcholine in the hippocampus and the AChE activity in the brain of rats. And oral administration of PPE increased dose-dependently the basal concentration of extracellular acetylcholine in the hippocampus of rats. PPE may be one of the more useful cholinesterase inhibitors for the treatment of Alzheimer's disease.

• 대한약침학회지
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• 제22권4호
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• pp.231-238
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• 2019

Objectives: Alzheimer's disease (AD), an overwhelming neurodegenerative disease, has deleterious effects on the brain that consequently causes memory loss and language impairment. This study was intended to investigate the neuroprotective activity of the two essential oils (EOs) from Iranian Pistacia khinjuk (PK) leaves and Allium sativum (AS) cloves against β-Amyloid 25-35 (Aβ25-35) induced elevation of cholinesterase enzymes in AD. Methods: The EOs of PK (PKEO) and AS (ASEO) were prepared and analyzed in terms of extraction yield, phenolic content, and cholinergic markers in vitro. Moreover, both were administered orally to adult male Wistar rats at concentrations of 1, 2, and 3%. The inhibitory potential of PKEO and ASEO was compared with Donepezil (0.75 mg/kg) against the high activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Results: PKEO reached an inhibition rate of 83.6% and 81.4% against AChE and BChE, respectively. ASEO had lower anti-cholinesterase activity (65.4% and 31.5% for the inhibition AChE and BChE). PKEO was found to have more phenolic content than ASEO. A significantly positive correlation was observed between the total phenolics and anti-cholinesterase potential. In rats, both EOs decreased the enzyme activity in a concentration-dependent manner. As compared with Donepezil, the significant difference in the AChE and BChE inhibition occurred as rats were treated with PKEO 3% (p < 0.05). Conclusion: It could be concluded that PKEO and ASEO are potent inhibitors of AChE and BChE in rats that hold promise to be used for the treatment of AD.

• Bulletin of the Korean Chemical Society
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• 제35권6호
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• pp.1681-1686
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• 2014

A series of hybrid molecules between (${\alpha}$)-lipoic acid (ALA) and 4-amino-1-benzyl piperidines were synthesized and their in vitro cholinesterase (acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) inhibitory activities were evaluated. Even though the parent compounds did not exhibit any inhibitory activity against cholinesterase (ChE) with the exception of compound 14 ($IC_{50}=255.26{\pm}4.41$ against BuChE), all hybrid molecules demonstrated BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, compound 17 was shown to be an effective inhibitor against both AChE ($IC_{50}=1.75{\pm}0.30{\mu}M$) and BuChE ($IC_{50}=5.61{\pm}1.25{\mu}M$) comparable to galantamine ($IC_{50}=1.7{\pm}0.9{\mu}M$ against AChE and $IC_{50}=9.4{\pm}2.5{\mu}M$ against BuChE). Inhibition kinetic studies using compound 17 indicated a mixed inhibition type for AChE and a noncompetitive inhibition type for BuChE. Its binding affinity ($K_i$) values to AChE and BuChE were $3.8{\pm}0.005{\mu}M$ and $7.0{\pm}0.04{\mu}M$, respectively.

• The Korean Journal of Physiology and Pharmacology
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• 제1권4호
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• pp.345-353
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• 1997

The effects of crude saponin (SAP) and alkaloid (ALK) fractions of Panax ginseng C.A. Meyer on the detrimental effects of electroconvulsive shock (ECS) and scopolamine on passive avoidance response (PAR) were studied in male Sprague-Dawley rats, referring their effects on the neuronal injury and plasticity of hippocampus in response to electrolytic lesion of left entorhinal cortex (ECL). The detrimental ECS effect on PAR was attenuated by pre- and post-treatments with SAP and ALK, respectively, or by pretreatment with aminoguanidine (AG), an inhibitor of diamine oxidase and NO synthase. And the detrimental scopolamine effect on PAR was also inhibited by pre-treatment with ALK or AG, and by post- treatment with SAP or ALK, respectively. On the 7th day after ECL, the brain sections stained by cresyl violet and by acetylcholinesterase (AChE) histochemistry, respectively, showed the chromatolysis and numeral decrease of neurons and the reduction of AChE reactivity in the hippocampus CA1 area and to a lesser extent, in the dentate gyrus. The neuronal cell death of the CA1 area was significantly reduced by SAP, ALK, or AG, and the reduction of AChE reactivity was significantly attenuated by SAP or ALK and to a lesser extent by AG. These results suggests that the protective effect of ginseng SAP and ALK fractions on ECS- or scopolamine-induced impairment of PAR may be ascribed in part to preservation of hippocampal neurons, particularly cholinergic neurons.

• 동의신경정신과학회지
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• 제20권2호
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• pp.1-17
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• 2009

Objectives : Alzheimer's disease(AD) is the most common form of dementia, which is characterized by progressive deterioration of memory and higher cortical functions that ultimately results in total degradation of intellectual and mental activities. Nokyongdaebo-tang(Lurongdabutang) has been usually used for the treatment for the deficiency syndrome dementia and amnesia. This experiment was designed to investigate the effect of the Nokyongdaebo-tang(Lurongdabutang) hot water extract on pathological AD model. Methods : The effects of the Nokyongdaebo-tang(Lurongdabutang) hot water extract on cultured spinal cord cells induced by ${\beta}$-amyloid were investigated. The effects of the Nokyongdaebo-tan(Lurongdabutang) hot water extract on the memory deficit mice induced by scopolamine were investigated. Results : 1. ${\beta}$-amyloid treatment on cultured spinal cord cells increased both GFAP-staining intensity of astrocytes and caspase 3 immunoreactivity on cultured cells. Then, Nokyongdaebo-tang(Lurongdabutang) treatment reduced the labeling intensity for both GFAP and caspase 3 proteins in culture cells. 2. Scopolamine treatment into mice increased levels of GFAP-positive astrocytes and caspase 3-labeled cells of the hippocampal subfields dentate hilar region, CA3 and CA1 area. In vivo administration of Nokyongdaebo-tang(Lurongdabutang) attenuated labeling intensity for those two proteins in the same hippocampal areas. Similar effects were observed by the treatment of galanthamine, an inhibitor of acetylcholinesterase. Conclusions : This experiment shows that the Nokyongdaebo-tang(Lurongdabutang) may play a protective role in damaged neural tissues. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. Nokyongdaebo-tang(Lurongdabutang) might be effective for the prevention and treatment of AD.

• 생약학회지
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• 제39권1호
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• pp.68-73
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• 2008

The present study represents the screening of the protective effects of herbal methanolic extracts from Baekdu mountain against tacrine-induced cytotoxicity in HepG2 cells. Tacrine is an acetylcholinesterase inhibitor, and used for the treatment of Alzheimer's disease. However, administration of tacrine for the treatment of Alzheimer's disease results in a reversible hepatotoxicity in 30-50% of patients, consequently limiting clinical use. Therefore, studies for natural products with protective effect on the tacrine-induced hepatotoxicity would be valuable as providing potential therapeutic use. 109 plant sources were collected in Baekdu mountain, and extracted with methanol. These extracts had been screened the protective effects against tacrine-induced cytotoxicity in HepG2 cells at the 100 and 300 ${\mu}g/ml$. Of these, ten methanolic extracts, roots of Ampelosis japonica, aerial parts of Berberis amurensis, aerial parts of Sedum aizoon, aerial parts of Lespedeza tomentosa, aerial parts of Lespedeza juncea, aerial parts of Hypenricum ascyron, stem barks of Syringa reticulata, fruits of Gleditsia japonica, aerial parts of Chamaenerion angustifolium, branches of Ginkgo biloba, showed significant protective effects against tacrine-induced cytotoxicity in HepG2 cells.

• 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.

• 대한한방부인과학회지
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• 제32권3호
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• pp.32-56
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• 2019

Objectives: The purpose of this study was to investigate the in vitro anti-inflammatory, anti-pruritic and antimicrobial effects of the three herbal prescription (EST, SCT, WDT), which has been traditionally used for treating leukorrhea induced by various infections in the female genital tract. Methods: In this experiment, the anti-inflammatory effects were evaluated by Nitric oxide (NO), $Interlukine-1{\beta}$ ($IL-1{\beta}$), Interlukine-2 (IL-2), Interlukine-6 (IL-6), Tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), Prostaglandin $E_2$ ($PGE_2$), Leukotriene $B_4$ ($LTB_4$) production amount and Inducible nitric oxide synthase (iNOS), Nuclear factor kappa B ($NF-{\kappa}B$), Cyclooxygenase-2 (COX-2) gene expression levels in RAW264.7 cells. And the anti-pruritic effects were evaluated by Histamine, Acetylcholine (ACh), Acetylcholinesterase (AChE), Substance P production amount in Mast cell/9 (MC/9) and Pheochromocytoma 12 (PC12) cells. The anti-microbial effect was measured by inhibition zone diameter on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger. Results: As a result of measuring anti-inflammatory efficacy, $IL-1{\beta}$, IL-2, IL-6, $TNF-{\alpha}$, $PGE_2$, and $LTB_4$ production amounts were significantly reduced in the EST, SCT, WDT extraction groups compared with the control group, and significantly decreased the amount of $NF-{\kappa}B$, iNOS, and COX-2 gene expression and the amount of Phospho-Inhibitor kappa B alpha ($p-I{\kappa}B-{\alpha}$)/Inhibitor kappa B alpha ($I{\kappa}B-{\alpha}$) and $NF-{\kappa}B$ p65 protein expression. In addition, As a result of measuring the anti-pruritic effect, the amounts of histamine, ACh and Substance P were significantly decreased, and AChE production was slightly decreased, but it's significance did not appear. Finally the anti-microbial effects of EST, SCT, WDT extraction groups against Pseudomonas aeruginosa, Candida albicans and Aspergillus niger was inhibited, however the growth of Escherichia coli and Staphylococcus aureus was not inhibited. Conclusions: These data suggest that EST, SCT, WDT can be used to treat patients with leukorrhea.

• 한국식품과학회지
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• 제49권6호
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• pp.668-675
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• 2017

본 연구에서는 눈개승마(Aruncus dioicus var. kamtschaticus)의 in vitro 산화방지활성 및 고당(intensive glucose)과 과산화수소($H_2O_2$)로 야기된 산화적 스트레스로부터의 뇌신경세포 손상에 대한 보호효과와 더불어 알파글루코사이드가수분해효소 및 아세틸콜린에스터가수분해효소 억제효과를 확인하였으며 또한 HPLC를 이용하여 주요 물질을 분석하였다. 눈개승마 아세트산에틸 분획물(ethylacetate fraction from Aruncus dioicus var. kamtschaticus: EFAD)은 매우 우수한 총 페놀화합물 함량(430.08 mg GAE/g)과 총 플라보노이드 함량(511.72 mg RE/g)을 나타냈으며, 높은 ABTS 라디칼 소거 활성과 과산화지방질생성물의 억제력을 확인하였다. 또한 고당(intensive glucose)과 과산화수소($H_2O_2$)로 야기된 뇌신경세포에서의 산화적 스트레스 및 이로 인한 뇌신경세포 사멸을 측정한 결과, 눈개승마 아세트산에틸 분획물(EFAD)의 유의적인 뇌신경세포 보호효과를 확인할 수 있었다. 추가적으로 다당류 분해 효소인 알파글루코사이드가수분해효소 억제효과 및 아세틸콜린 분해 효소인 아세틸콜린에스터가수분해효소 억제효과를 살펴봄으로써 혈당 상승 억제효과와 뇌신경전달물질의 세포 내 유지 효과를 확인하였다. 마지막으로 눈개승마 아세트산에틸 분획물(EFAD)의 주요 페놀성 물질을 확인하기 위해 HPLC분석을 한 결과 카페산으로 추정되었다. 본 연구 결과들을 고려할 때, 눈개승마는 고혈당 지연 또는 개선을 통한 고혈당 예방 소재로서의 가능성뿐만 아니라 이로 인해 야기되는 산화적 스트레스로부터 뇌신경 세포를 보호함으로써 고혈당에 의한 대사성 뇌신경질환 예방 소재로도 활용 가능성이 있을 것이라 판단된다.