• Journal of Oriental Neuropsychiatry
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• v.9 no.1
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• pp.1-24
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• 1998

The effects of Hyungbangjiwhangrang on the enhancement of learning and memory of AD model rats were studied with Morris water maze and radial arm maze. Sample group was electrolytically lesioned on nbM, and then daily treated with the medicine for two months. Control group with nbM lesion, and sham group with the sham operation were treated the vehicle for same duration. The following results were observed.1. As the learning trials of Morris water maze processed repeatedly, sham group achiened 201.64${\pm}$33.13 seconds in 1st trial, 153.14${\pm}$61.80 seconds in 2nd, 106.21${\pm}$46.81 seconds in 3rd, 76.64${\pm}$48.40 seconds in 4th, and 52.29${\pm}$38.25 seconds in 5th. The control group achieved 224.08${\pm}$29.16 in 1st trial, 191.77${\pm}$67.97 seconds in 2nd, 177.77${\pm}$65.44 seconds in 3rd, 140.92${\pm}$68.27 seconds in 4th, and 126.46${\pm}$79.15 seconds in 5th. The sample group achieved 223.36${\pm}$23.33 seconds in 1st trial, 215.86${\pm}$38.93 seconds in 2nd, 190.79${\pm}$51.57 seconds in 3rd, 155.79${\pm}$62.67 seconds in 4th, and 127.93${\pm}$62.11 seconds in 5th. Therefore, these data shows that all three groups were improved in learning capacity as trials were repeated, but the shame group showed prominent improvement in learning compared with the control group(p<0.05).2. In memory retention test of Morris water maze that counts the staying time in the target area, sham group stayed for 15.36${\pm}$5.39 seconds, the control group stayed for 5.54${\pm}$5.64 seconds, and the sample group stayed for 7.43${\pm}$6.09 seconds. The analysis of the memory retention data shows that the sham group marked more significant improvement stati- stically in memory retention compared with the control group(p<0.05).3. In the learning of radial arm maze, the number and rate of animals that arrive the learning criteria amounted 12 out of 14, 85.7% in sham group, 4 out of 13, 30.8% in the control group, and 10 out of 14, 71.4% in the sample group So, the sample group shows better learning capacity significantly compared with the control group(p<0.05). With the experimental results above, Hyungbangjiwhangtang can be supposed to have the improving effects on the learning and memory of AD rats induced by eletronical injury of nbM.

• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.70-78
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• 2009

Coptis japonica (C. japonica) is a perennial medicinal plant that has anti-inflammatory activity. C. japonica contains numerous biologically active alkaloids including berberine, palmatine, epi-berberine, and coptisine. The most well-known anti-inflammatory principal in C. japonica is berberine. For example, berberine has been implicated in the inhibition of iNOS induction by cytokines in microglial cells. However, the efficacies of other alkaloids components on microglial activation were not investigated yet. In this study, we investigated the effects of three alkaloids (palmatine, epi-berberine and coptisine) from C. japonica on lipopolysaccharide (LPS)-induced microglial activation. BV2 microglial cells were immunostimulated with LPS and then the production of several inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) were examined as well as the phosphorylation status of Erk1/2 mitogen activated protein kinase (MAPK). Palmatine and to a lesser extent epi-berberine and coptisine, significantly reduced the release of NO, which was mediated by the inhibition of LPS-stimulated mRNA and protein induction of inducible nitric oxide synthase (iNOS) from BV2 microglia. In addition to NO, palmatine inhibited MMP-9 enzymatic activity and mRNA induction by LPS. Palmatine also inhibited the increase in the LPS-induced MMP-9 promoter activity determined by MMP-9 promoter luciferase reporter assay. LPS stimulation increased Erk1/2 phosphorylation in BV2 cells and these alkaloids inhibited the LPS-induced phosphorylation of Erk1/2. The anti-inflammatory effect of palmatine in LPS-stimulated microglia may suggest the potential use of the alkaloids in the modulation of neuroinflammatory responses, which might be important in the pathophysiological events of several neurological diseases including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD) and stroke.

• Journal of Oriental Neuropsychiatry
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• v.10 no.1
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• pp.17-38
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• 1999

The effects of Sahyangsohapwon on the affective reactivity of rats were studied with open-field behavior. Sample group was treated with the medicine for 8 weeks, whereas control group was treated with the vehicle. The effects of Sahyangsohapwon on the enhancement of learning and memory of AD model rats were studied with two-way avoidance task. Sample group electrically lesioned on nbM(nucleus basalis of Meynert) was treated with the medicine for 8 weeks, whereas control group with nbM lesion and sham group with the sham operation were treated with the vehicle. 1. In the open-field behavior task, the start latency from start box was measured $27.08{\pm}7.51sec$ in control group, $23.15{\pm}5.98sec$ in sample group. Rats in sample group showed a tendency of shortened latency going out to a strange place compared with those in control group, but with no statistical significance(p>0.05). 2. In the open-field behavior task, the number of locomotion crossing the grid lines was measured $84.54{\pm}3.55$ in control group, $116.93{\pm}6.41$ in sample group. There was an increased locomotion in sample group compared with control group with statistical significance(p<0.01). This can be interpreted as rats in sample group showed lowerd anxiety under a strange environment. 3. In the open-field behavior task, the rearing number was measured $7.46{\pm}0.57$ in control group, $10.13{\pm}0.95$ in sample group. There was an increased rearing in sample group compared with control group with statistical significance(p<0.05). This can also be interpreted as rats in sample group showed lowerd anxiety under a strange environment. 4. In the open-field behavior task, the number of crossing behavior was measured $5.54{\pm}1.50$ in control group, $9.20{\pm}1.67$ in sample group. There was a increasing tendency of crossing behavior in sample group compared with control group, but with no statistical significance(p<0.05). 5. In the open-field behavior task, the total activity was measured $97.54{\pm}4.70$ in control group, $136.27{\pm}792$ in sample group. There was an increased total activity in sample group compared with control group with statistical significance(p<0.01). This can also be interpreted as rats in sample group showed lowerd anxiety under a strange environment. 6. In the analysis of effects on the learning and memory in AD model rats with two-way avoidance task, the response latency was measured $6717{\pm}134msec$ in the 1st session, $5416{\pm}160msec$ in the 2nd session, $5252{\pm}148msec$ in the 3rd session in control group. It was measured $6724{\pm}155msec$ in the 1st session, $4642{\pm}139msec$ in the 2nd session, $4914{\pm}148msec$ in the 3rd session in sample group and $4357{\pm}144msec$ in the 1st session, $3125{\pm}115msec$ in the 2nd session, $3091{\pm}98msec$ in the 3rd session in sham group. There were differences between sham group and nbM lesioned groups with statistical significance in post hoc analysis(p<0.000). And in the 2nd session, there was a reduction of latency in sample group compared with control group with statistical significance (p<0.000). This showed that sample group had better learning capacity than control group. 7. In the analysis of effects on the learning and memory in AD model rats with two-way avoidance task, the number of avoidance response was measured $5.85{\pm}1.41$ in the 1st session, $14.23{\pm}2.89$ in the 2nd session, $15.69{\pm}2.56$ in the 3rd session in control group. It was measured $7.92{\pm}1.94$ in the 1st session, $16.83{\pm}2.29$ in the 2nd session, $15.42{\pm}2.81$ in the 3rd session in sample group and $14.38{\pm}1.62$ in the 1st session, $22.88{\pm}0.89$ in the 2nd session, $23.88{\pm}1.64$ in the 3rd session in sham group. There were differences between sham group and nbM lesioned groups with statistical significance in post hoc analysis(p<0.001). But between control and sample group, there was no significant difference. With the experimental results above, Sahyangsohapwon can be supposed to have the enhancing effects on the affect reactivity and learning with memory of AD model rats induced by electrolyte injury of nbM.

• The Journal of Korean Medicine
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• v.27 no.2 s.66
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• pp.122-133
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• 2006

Objectives : The amyloid $\beta$-protein ($A\beta$) is the principal component of the senile plaques characteristic of Alzheimer's disease (AD) and elicits a toxic effect on neurons in vitro and in vivo. Many environmental factors including antioxidants and proteoglycans modify $A{\beta}toxicity$. In this study, we have investigated the protective effects of water- and organic solvent-extracts of Hemerocallis fulva root fractions pre-extracted with methanol on $A\beta$-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. Methods : For this study, we used MTT reduction assay for detection of protective effects of water- and organic solvent-extracts of Hemerocallis fulva root fractions pre-extracted with methanol on $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells. We also used cell-based $\beta$-secretase assay system to investigate the inhibitory effect of water- and organic solvent-extracts of Hemerocallis fulva root on $\beta$-secretase activity. Results : We previously reported that methanol extracts of Hemerocallis fulva root strongly attenuated cytotoxicity induced by the three $A\beta$ fragments ($A{\beta}_{25-35},\;A{\beta}_{1-42}\;A{\beta}_{1-43}$) to both SK-N-MC and PC12 cells. In the present study, we found that butanol-, ethylacetate-, chloroform-, and water-extracts of Hemerocallis fulva root fractions pre-extracted with methanol had strong protective effects against $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells and inhibitory potency to $\beta$-secretase activity. Conclusion : These results suggest that butanol-, ethylacetate-, chloroform-, and water-extracts of Hemerocallis fulva root fractions pre-extracted with methanol may contain the protective component(s) against $A\beta$-induced cell death in PC12 cells as well as inhibitory component(s) to $\beta$-secretase activity.

• Journal of Life Science
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• v.30 no.4
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• pp.331-342
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• 2020

The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.

• Korean Journal of Food Science and Technology
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• v.41 no.4
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• pp.435-440
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• 2009

Acetylcholinesterase (AChE) inhibitors, which enhance cholinergic transmission by reducing the enzymatic degradation of acetylcholine, are the only source of the compound that is currently approved for the treatment of Alzheimer's disease (AD). In these experiments, the concentration samples of green tea extracts were 100, 500, and 1,000 ${\mu}g$/mL. Among them, the highest concentration (1,000 ${\mu}g$/mL) of fresh green tea extracts showed the most potent inhibitory effect on AChE by reducing more than 40% of enzyme activity, and in a concentration-dependent pattern. In addition, we examined the effect of other storing conditions on AChE inhibition. In order to maintain storage for 3 months, the materials were held at the certain storing conditions of temperature (room temperature, 4 and $-20^{\circ}C$) and for water activity (0.81, 0.69, and 0.23). In these storing conditions, the difference in temperature did not contribute to the AChE inhibitory effect. Our presented data showed that the AChE inhibitory effect was affected by the concentration of green tea extract and by water activity (0.81). These results suggest that green tea may serve as a potential dietary source of AChE inhibitor.

• Nutrition Research and Practice
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• v.12 no.3
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• pp.191-198
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• 2018

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.4
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• pp.272-279
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• 2007

Purpose: The aim of this study was to evaluate the discriminating nature of $^{123}I-FP-CIT$ SPECT in patients with parkinsonism. Methods: $^{123}I-FP-CIT$ SPECT images acquired from the 18 normal controls; NC ($60.4{\pm}10.0$ yr) and 237 patients with parkinsonism ($65.9{\pm}9.2$ yr) were analyzed. From spatialIy normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric Index (ASI) were measured. Results: BPs of NC $3.37{\pm}0.57,\; 3.10{\pm}0.41,\; 3.23{\pm}0.48$ for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET ($3.31{\pm}0.64,\; 3.06{\pm}0.61,\; 3.14{\pm}0.63$) and Alzheimer's disease; AD (3.33 $\pm$0.60, 3.29$\pm$0.79, 3.31$\pm$0.70), but were higher than those of Parkinson's disease; PD (1.92$\pm$0.74, 1.39$\pm$0.68, 1.64$\pm$0.68), multiple system atrophy; MSA (2.36$\pm$1.07, 2.16$\pm$0.91, 2.26$\pm$0.96), and dementia with Lewy body; DLB (1.95$\pm$0.72, 1.64$\pm$0.65, 1.79$\pm$0.66)(p<0.005). PD had statisticalIy lower values of PER and higher values of ASI than those of NC (p<0.005). And PD had significantIy lower value of PCR, higher ASI and lower BP in the putamen and whole striatum than MSA (p<0.05). Conclusion: Dopamine transporter image of $^{123}I-FP-CIT$ SPECT was a good value in differential diagnosis of parkinsonism.

• Journal of the Korean Society of Radiology
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• v.84 no.3
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• pp.638-652
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• 2023

Purpose To investigate the MRI markers for the prediction of amyloid β (Aβ)-positivity in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to evaluate the differences in MRI markers between Aβ-positive (Aβ [+]) and -negative groups using the machine learning (ML) method. Materials and Methods This study included 139 patients with MCI and AD who underwent amyloid PET-CT and brain MRI. Patients were divided into Aβ (+) (n = 84) and Aβ-negative (n = 55) groups. Visual analysis was performed with the Fazekas scale of white matter hyperintensity (WMH) and cerebral microbleeds (CMB) scores. The WMH volume and regional brain volume were quantitatively measured. The multivariable logistic regression and ML using support vector machine, and logistic regression were used to identify the best MRI predictors of Aβ-positivity. Results The Fazekas scale of WMH (p = 0.02) and CMB scores (p = 0.04) were higher in Aβ (+). The volumes of hippocampus, entorhinal cortex, and precuneus were smaller in Aβ (+) (p < 0.05). The third ventricle volume was larger in Aβ (+) (p = 0.002). The logistic regression of ML showed a good accuracy (81.1%) with mini-mental state examination (MMSE) and regional brain volumes. Conclusion The application of ML using the MMSE, third ventricle, and hippocampal volume is helpful in predicting Aβ-positivity with a good accuracy.

• Journal of Life Science
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• v.29 no.2
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• pp.173-180
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• 2019

Amyloid ${\beta}$-protein ($A{\beta}$) is the principal component of senile plaques characteristic of Alzheimer's disease (AD) and elicits a toxic effect on neurons in vitro and in vivo. Many environmental factors, including antioxidants and proteoglycans, modify $A{\beta}$ toxicity. It is worthwhile to isolate novel natural compounds that could prove therapeutic for patients with AD without causing detrimental side effects. In this study, we investigated the in vitro neuroprotective effects of the ethyl acetate fraction of methanol extract of Ophiophogon japonicas (OJEA fraction). We used an MTT reduction assay to detect protective effects of the OJEA fraction on $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells. We also used a cell-based ${\beta}$-secretase assay system to investigate the inhibitory effect of the OJEA fraction on ${\beta}$-secretase activity. In addition, we performed an in vitro lipid peroxidation assay to evaluate the protective effect of the OJEA fraction against oxidative stress induced by $A{\beta}_{25-35}$ in PC12 cells. The OJEA fraction had strong protective effects against $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells and was strongly inhibitory to ${\beta}$-secretase activity, which resulted in the attenuation of $A{\beta}$ generation. In addition, the OJEA fraction significantly decreased malondialdehyde (MDA) content, which is induced by the exposure of PC12 cells to $A{\beta}_{25-35}$. Our results suggested that the OJEA fraction contained active compounds exhibiting a neuroprotective effect on $A{\beta}$ toxicity.