• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.43-51
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• 2006

This experiment was designed to investigate the effect of Amomum villosum(AMV) on the Alzheimer's disease. The effects of AMV extract on amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell line treated by amyloid $\beta$ protein($A{\beta}$) : IL-$1{\beta}$, IL-6, TNF-$\alpha$ mRNA of THP-1 cell line treated by lipopolysaccharide(LPS) : AChE activity of PC-12 cell lysate treated by $A{\beta}$ : serum glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine : behavior of memory deficit mice induced by scopolamine were investigated, respectively. AMV extract suppressed APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$ : IL-$1{\beta}$, IL-6, TNF-$\alpha$ mRNA in THP-1 cell treated by LPS , AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. AMV extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. AMV extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. According to the above results, it is suggested that AMV extract might be usefully applied for prevention and treatment of Alzheimer's disease.

• Animal cells and systems
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• v.16 no.3
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• pp.198-206
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• 2012

Anxiety in zebrafish can be determined by examining their bottom-dwelling and light-avoidance behavior. This study determines the effects of physostigmine and scopolamine on anxiety in zebrafish by measuring swimming frequency for three horizontal layers and three vertical columns of a water test tank illuminated by a light source located above the central surface of the tank. In the 1 h session, zebrafish in the control group preferred the bottom layer the most and the center column the least. Zebrafish treated with 2-20 ${\mu}M$ physostigmine were more likely to prefer the to layer than controls, and there were significant pairwise differences between physostigmine-treated zebrafish and controls, indicating the anxiolytic effect of physostigmine. Further, 10 and $20{\mu}M$ physostigmine-treated zebrafish no longer avoided the center column. Scopolamine had no anxiolytic effect on bottom-dwelling and light-avoidance behaviors but suppressed the anxiolytic effect of physostigmine. In terms of their preference for various zones formed by layers and columns, zebrafish in the control group preferred the bottom left and right zones the most. Physostigmine had a positive effect on the preference for the top center zone, which was suppressed by scopolamine pretreatment. The results suggest that the level of anxiety in zebrafish can be reduced by activating acetylcholinergic neurotransmitter systems, which is mediated in part by muscarinic receptors.

• Journal of Oriental Neuropsychiatry
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• v.29 no.4
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• pp.207-221
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• 2018

Objectives: The objective of this study was to observe the anti-amnesic effects of Yukmijihwang-tang (YMJHT), on the scopolamine (Sco)-induced memory impairment in C57BL/6 mice through its favorable acetylcholine (ACh). Also, to observe acetylcholinesterase (AChE) activity, Choline acetyltransferase (ChAT) mRNA expressions, and antioxidant effect. Methods: Six groups, with a total of 20 normal and 100 Sco treated mice were selected based on their body weights after 1 week of acclimatization, were used in this study as follows. Half of the mice in each group were used for passive avoidance task tests and hippocampus ACh content, AChE activity and ChAT mRNA expression measurement, and the remaining half in each group used for Morris water maze test and measurement of cerebral antioxidant defense system. Results: Amnesia due to AChE activations and destroyed cerebral cortex antioxidant defense systems were markedly and dose-dependently inhibited after 28 days of continuous oral pre-treatment with YMJHT 400, 200 and 100 mg/kg, respectively. The overall effects of YMJHT 400 mg/kg were similar to those of tacrine 10 mg/kg. Conclusions: Based on the results, it was established that oral administration of YMJHT favorably alleviates Sco-induced memory impairment, through preservation of ACh, mediated by up-regulation of ChAT mRNA expressions and related AChE inhibition and augmentation of cerebral antioxidant defense system, at least in a condition of this experiment. The overall effects of YMJHT 400 mg/kg were similar to those of tacrine 10 mg/kg.

• Journal of Oriental Neuropsychiatry
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• v.30 no.3
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• pp.221-235
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• 2019

Objectives: The purpose of this study was to confirm the anti-amnesic effects of Bunsimgieum (BSGE) through its favorable acetylcholine (ACh) and, acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT) mRNA expressions, and antioxidant effect on scopolamine (Sco)-induced memory impairment in C57BL/6 mice. Methods: Six groups, a total of 20 intact or 100 Sco-induced mice were used in this study, based on their body weight. Half of each group underwent passive avoidance tests and the measurement of hippocampus AChE activity, ACh content, and ChAT mRNA expression, The remaining half of each group underwent a Morris water-maze test and antioxidant defense system measurement as well. Results: Significant reductions in the step-through latency times from the passive avoidance test and reductions in the escape latency times from the Morris water-maze test were observed with increases of hippocampal AChE activities and, reductions in ACh contents and ChAT mRNA expression in hippocampus, as a result of Sco intraperitoneal treatment, in this study. Additionally, the increases in cerebral cortical MDA levels and, reductions in GSH contents, SOD activities, and CAT activities were demonstrated in the Sco control mice compared with the intact vehicle control mice, respectively. However, 28 days of consecutive oral pre-treatment of BSGE hot water extracts of 400, 200, and 100 mg/kg, respectively, markedly and dose-dependently inhibited Sco treatment-related amnesia. Conclusions: The results demonstrate that the oral administration of BSGE hot water extracts reduces Sco-induced memory impairment, through preserving ACh, related to ChAT mRNA expressions, causes AChE inhibition, and enhances the cerebral antioxidant defense system.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.108-118
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• 2021

Background: Korean ginseng (Panax ginseng Meyer) contains a variety of ginsenosides that can be metabolized to a biologically active substance, compound K. Previous research showed that compound K could be enriched in the red ginseng extract (RGE) after hydrolysis by pectinase. The current study investigated whether the enzymatically hydrolyzed red ginseng extract (HRGE) containing a notable level of compound K has cognitive improving and neuroprotective effects. Methods: A scopolamine-induced hypomnesic mouse model was subjected to behavioral tasks, such as the Y-maze, passive avoidance, and the Morris water maze tests. After sacrificing the mice, the brains were collected, histologically examined (hematoxylin and eosin staining), and the expressions of antioxidant proteins analyzed by western blot. Results: Behavioral assessment indicated that the oral administration of HRGE at a dosage of 300 mg/kg body weight reversed scopolamine-induced learning and memory deficits. Histological examination demonstrated that the hippocampal damage observed in scopolamine-treated mouse brains was reduced by HRGE administration. In addition, HRGE administration increased the expression of nuclear-factor-E2-related factor 2 and its downstream antioxidant enzymes NAD(P)H:quinone oxidoreductase and heme oxygenase-1 in hippocampal tissue homogenates. An in vitro assay using HT22 mouse hippocampal neuronal cells demonstrated that HRGE treatment attenuated glutamate-induced cytotoxicity by decreasing the intracellular levels of reactive oxygen species. Conclusion: These findings suggest that HRGE administration can effectively alleviate hippocampus-mediated cognitive impairment, possibly through cytoprotective mechanisms, preventing oxidative-stress-induced neuronal cell death via the upregulation of phase 2 antioxidant molecules.

• Korean Journal of Agricultural Science
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• v.49 no.1
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• pp.137-149
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• 2022

We investigated the effects of Cirsium japonicum var. maackii (CJM) against oxidative stress-induced C6 glial cells and cognitive impairment in mice. To evaluate the anti-oxidative effect of the extract and fractions from CJM, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), reactive oxygen species (ROS), and nitric oxide (NO) assays were conducted in H₂O₂-treated C6 glial cells. Furthermore, we identified the protective mechanisms of CJM with a scopolamine-treated mice model. The results revealed that H₂O₂ decreased the cell viability in C6 glial cells, indicating that H₂O₂ induced oxidative stress in glial cells. However, CJM fractions significantly increased cell viability in H₂O₂-treated C6 glial cells, which suggested that CJM protected against oxidative stress. CJM extract and fractions also reduced ROS and NO production, which were increased by H₂O₂ in C6 glial cells. In particular, the EtOAc fraction from CJM (EACJM) effectively protected against oxidative stress by increasing the cell viability and decreasing ROS and NO. Therefore, we carried out further in vivo experiments with EACJM. Scopolamine caused increases of ROS, thiobarbituric acid reactive substances (TBARS), and NO production. However, EACJM effectively alleviated ROS, TBARS, and NO levels compared to scopolamine-injected mice. In addition, EACJM up-regulated protein expressions of superoxide dismutase and glutathione peroxidase, indicating that EACJM enhanced the antioxidative system. Our results demonstrated that CJM had protective effects against oxidative stress in glial cells and memory dysfunction in mice. Based on these results, we propose that CJM could be a potential AD preventive and therapeutic agent.

• Food Science and Biotechnology
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• v.17 no.2
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• pp.384-388
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• 2008

Alzheimer's disease (AD) is the most common neurodegenerative disorder and is responsible for more than 50% of all dementia cases. There is significant interest in finding new sources of compounds that inhibit acetylcholinesterase (AChE) to be used in the treatment of AD, since only a few AChE inhibitors, such as galanthamine, physostigmine, and tacrine, are available for clinical use. In the present study, ICR mice were treated with a 1 mg/kg scopolamine, which caused impaired cognitive ability. The steady consumption of a water extract of Chrysanthemum indicum Linne flowers for 3 months significantly prevented the scopolamine induced deficit of the spatial cognitive capability of mice. It also improved long-term memory in mice with amnesia induced by scopolamine, as assessed by the Morris water maze and passive avoidance tests. In addition, water extract consumption significantly decreased AChE activity in mouse brain, leading to inhibition of acetylcholine hydrolysis.

• Korean Journal of Medicinal Crop Science
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• v.12 no.2
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• pp.123-128
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• 2004

Hyoscyamine and scopolamine are two most common tropane alkaloids found in the Solanaceae. The pEB expression vector carrying Nspmt gene was transformed to Agrobacterium rhizogenes. The growth of transgenic hairy roots were approximately to 80% of the wild type root. Transgenic hairy roots are less developed on only their branch roots than those of the wild type root. The extracts from Nspmt transgenic hairy root lines, 3 and 5 contained between 3.52 and 4.23 mg/g dry weight as hyoscyamine and did between 5.23 to 6.40 mg/g dry weight as scopolamine. These results showed that the overexpression of the pmt gene enhanced tropane alkaloids production of S. parviflora transformed roots and this improvement affected both hyoscyamine and scopolamine production.

• Journal of Acupuncture Research
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• v.23 no.3
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• pp.117-127
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• 2006

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disease associated with aging in the human population. This disease is characterized by the following 4 structural changes : Atrophy of the Cortex, Parasympathetic, and other neural cells, the existence of Neurofibrillary tangles (NFTs), and the accumulation of Senile plaques. NFTs and Senile plaques is known to be the index of this disease. Senile plaques disturbs the neutro transmission and depletes of Acetylcholine. So, Recovery of Acetylcholine is the primal objective for treating Alzheimer's disease. So, Inhibiting the activity of Acetylcholine Esterase (AChE), which causes the hydrolysus of acetylcholine into choline and acetate, can be seen as a key role for treating Alzheimer's disease. Increasing body of evidence has been demonstrated that Bee Venom Acupuncture (BV) could compete with complex protein involving in multiple step of $NF-_{\kappa}B$ activation and exert the anti-inflammatory potential of combined inhibition of the prostanoid and nitric oxide synthesis systems by inhibition of IKK and $NF-_{\kappa}B$. BV dose-dependently attenuated Scopolamine-induced Acetylcholine esterase activities in cerebral cortex and hippocampus of the mice brain. This study therefore suggests that BV acupuncture method may be useful for prevention of development or progression of AD.

• Advances in Traditional Medicine
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• v.7 no.2
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• pp.182-190
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• 2007

Alzheimer's disease is a neurodegenerative disorder associated with a decline in cognitive abilities. Dementia is one of the aged related mental problems and a characteristic symptom of Alzheimer's disease. Nootropic agents like piracetam and cholinesterase inhibitors like $Donepezil^{\circledR}$ are used in situations where there is organic disorder in learning abilities, but the resulting side-effects associated with these agents have limited their utility. Foeniculum (F.) vulgare Linn. is widely used in Indian traditional systems of medicines and also as a house remedy for nervous debility. The present work was undertaken to assess the potential of F. vulgare as a nootropic and anti-cholinesterase agent in mice. Exteroceptive behavioral models such as Elevated plus maze and Passive avoidance paradigm were employed to assess short term and long term memory in mice. To delineate the possible mechanism through which F. vulgare elicits the anti-amnesic effects, its influence on central cholinergic activity was studied by estimating the whole brain acetylcholinesterase activity. Pretreatment of methanolic extract of fruits of F. vulgare Linn. for 8 successive days, ameliorated the amnesic effect of scopolamine (0.4 mg/kg) and aging induced memory deficits in mice. F. vulgare extract significantly decreased transfer latencies of young mice and aged mice, increased step down latency and exhibited significant anti-acetyl cholinesterase effects, when compared to piracetam, scopolamine and control groups of mice. F. vulgare might prove to be a useful memory restorative agent in the treatment of dementia seen in the elderly.