Dong Hyun Park

Kyung Hee University, Sŏul, Seoul, South Korea

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Publications (9)24.17 Total impact

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    ABSTRACT: Alzheimer's disease, one of the most common forms of dementia, is a progressive neurodegenerative disorder symptomatically characterized by declines in memory and cognitive abilities. To date, the successful therapeutic strategy to treat AD is maintaining levels of acetylcholine by inhibiting acetylcholinesterase (AChE). In the present study, coumarin derivatives were designed and synthesized as AChE inhibitors based on the lead structure of scopoletin. Of those synthesized, pyrrolidine-substituted coumarins 3b and 3f showed ca. 160-fold higher AChE inhibitory activities than scopoletin. These compounds also ameliorated scopolamine-induced memory deficit in mice when administered orally at the dose of 1 and 2mg/kg.
    Bioorganic & medicinal chemistry 01/2014; · 2.82 Impact Factor
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    ABSTRACT: Opuntia ficus-indica var. saboten Makino (Cactaceae) is used to treat burns, edema, dyspepsia, and asthma in traditional medicine. The present study investigated the beneficial effects of the n-butanolic extract of O. ficus-indica var. saboten (BOF) on memory performance in mice and attempts to uncover the mechanisms underlying its action. Memory performance was assessed with the passive avoidance task, and western blotting and immunohistochemistry were used to measure changes in protein expression and cell survival. After the oral administration of BOF for 7 days, the latency time in the passive avoidance task was significantly increased relative to vehicle-treated controls (P<0.05). Western blotting revealed that the expression levels of brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element binding-protein (pCREB), and phosphorylated extracellular signal-regulated kinase (pERK) 1/2 were significantly increased in hippocampal tissue after 7 days of BOF administration (P<0.05). Doublecortin and 5-bromo-2-deoxyuridine immunostaining also revealed that BOF significantly enhanced the survival of immature neurons, but did not affect neuronal cell proliferation in the subgranular zone of the hippocampal dentate gyrus. These results suggest that the subchronic administration of BOF enhances long-term memory, and that this effect is partially mediated by ERK-CREB-BDNF signaling and the survival of immature neurons.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 08/2010; 34(6):1011-7. · 3.55 Impact Factor
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    ABSTRACT: Quercetin is a naturally occurring dietary flavonol and several reports have shown that quercetin substantially affects cognitive function in disease models, which suggests that quercetin might be a useful agent for treatment of memory dysfunction. However, only one report has examined the effects of quercetin on normal cognitive function. In the present study, we investigated the potential deleterious effects of quercetin on normal cognitive function using Western blot assays and the following behavioral tasks: passive avoidance, Y-maze, and Morris water maze. In the passive avoidance task, pre-acquisition administration of quercetin (10, 20, or 40 mg/kg, p.o.) caused significant cognitive impairments in mice (P < 0.05 or P < 0.01). Quercetin-treated groups (10, 20, or 40 mg/kg, p.o.) also showed significant memory impairments compared with the control group in the Y-maze task (P < 0.05). In the Morris water maze task, there were no significant differences among the groups during training trial sessions, but at the probe trial session, the quercetin-treated group (40 mg/kg, p.o.) spent significantly less time in the target quadrant than did the control group (P < 0.05). In Western blot assays of hippocampal tissue, we found that quercetin-treated groups showed decreased expression of phosphorylated Akt (pAkt), phosphorylated calcium-calmodulin kinase II (pCaMKII), and phosphorylated cyclic AMP response element-binding protein (pCREB). These results suggest that acute administration of quercetin impairs cognitive function by suppression of pAkt and pCaMKII, which, in turn, decreases pCREB expression in the hippocampus.
    Toxicology Letters 05/2010; 197(2):97-105. · 3.15 Impact Factor
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    ABSTRACT: Excitotoxin induces neurodegeneration via glutamatergic activation or oxidative stress, which means that the blockade of glutamate receptors and the scavenging of free radicals are potential therapeutic targets in neurodegenerative diseases. Sinapic acid (SA) has a GABA(A) receptor agonistic property and free radical scavenging activity. We investigated the neuroprotective effects of SA on kainic acid (KA)-induced hippocampal brain damage in mice. SA (10 mg/kg) by oral administration has an anticonvulsant effect on KA-induced seizure-like behavior. Moreover, SA (10 mg/kg) significantly attenuated KA-induced neuronal cell death in the CA1 and CA3 hippocampal regions when administered as late as 6 h after KA. In addition, flumazenil, a GABA(A) antagonist, blocked the effect of SA administered immediately after KA but not the effect of SA administered 6 h after KA. This late protective effect of SA was accompanied by reduced levels of reactive gliosis, inducible nitric oxide synthase expression, and nitrotyrosine formation in the hippocampus. In the passive avoidance task, KA-induced memory impairments were ameliorated by SA. These results suggest that the potential therapeutic effect of SA is due to its attenuation of KA-induced neuronal damage in the brain via its anti-convulsive activity through GABA(A) receptor activation and radical scavenging activity.
    Neuropharmacology 04/2010; 59(1-2):20-30. · 4.11 Impact Factor
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    ABSTRACT: The fruit of Euphoria longan (Lour.) Steud. (Sapindaceae) is sweet and edible. Dried Euphoria longan fruit is prescribed as a tonic and for the treatment of forgetfulness, insomnia, or palpitations caused by fright in traditional Chinese medicine. The effects of aqueous extract of Euphoria longan fruit (ELE) on learning and memory and their underlying mechanisms were investigated. Aqueous extract of Euphoria longan fruit (ELE) was administered to ICR mice for 14 days. Piracetam was used as a positive control for its known memory-enhancing effects. Memory performances were assessed using the passive avoidance task. The expressions of phosphorylated extracellular signal-regulated kinase (pERK) 1/2, phosphorylated cAMP response element binding protein (pCREB), brain-derived neurotrophic factor (BDNF), doublecortin (DCX) and the incorporation of 5-bromo-2-deoxyuridine (BrdU) in hippocampal dentate gyrus and CA1 regions were investigated using immunohistochemical methods. The step-through latency in the ELE-treated group was significantly increased compared with that in the vehicle-treated controls (P<0.05) in the passive avoidance task. Piracetam-treated group also showed enhanced cognitive performaces in the passive avoidance task. Immunohistochemical studies revealed that the number of cells immunopositive for BDNF, pCREB, or pERK 1/2 was significantly increased in the hippocampal dentate gyrus and CA1 regions after ELE treatment for 14 days (P<0.05). DCX and BrdU immunostaining also revealed that ELE significantly enhanced immature neuronal survival, but not neuronal cell proliferation in the subgranular zone of the dentate gyrus. The present results suggest that subchronic administration of aqueous extract of Euphoria longan fruit enhances learning and memory, and that its beneficial effects are mediated, in part, by BDNF expression and immature neuronal survival.
    Journal of ethnopharmacology 03/2010; 128(1):160-5. · 2.32 Impact Factor
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    ABSTRACT: It is well known that inhibition of prolyl oligopeptidase (POP) is involved in memory-related function. In this study, we observed that rosmarinic acid (RA) inhibits POP activity with an IC(50) of 63.7 microM. Subsequently, we investigated the cognitive-enhancing effects of RA employing the Morris water maze paradigm. The results demonstrated that RA is non-competitive POP inhibitor and that acute and subchronic RA treatments showed an inverted U-shaped dose-response curve in the platform crossings. Furthermore, chronic RA treatment significantly increased the platform crossings. These results suggest that RA has a cognitive-enhancing effect which may be mediated by inhibition of POP.
    Fitoterapia 03/2010; 81(6):644-8. · 2.23 Impact Factor
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    ABSTRACT: Prunella vulgaris var. lilacina is widely distributed in Korea, Japan, China, and Europe, and its flowers are used to treat inflammation in traditional Chinese medicine. In the present study, we studied the effects of the ethanolic extract of the flower of P. vulgaris var. lilacina (EEPV) on drug-induced learning and memory impairment using the passive avoidance, the Y-maze, and the Morris water maze tasks in mice. EEPV (25 or 50 mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairments in the passive avoidance and Y-maze tasks (P<0.05). In the Morris water maze task, EEPV (25 mg/kg, p.o.) significantly shortened escape latencies in training-trials. Furthermore, swimming times within the target zone during the probe-trial were significantly increased as compared with scopolamine-treated mice (P<0.05). In addition, the reduced latency induced by MK-801 treatment in the passive avoidance task was ameliorated by EEPV (25 mg/kg, p.o.) (P<0.05). Additionally, the ameliorating effect of EEPV on scopolamine-induced memory dysfunction was antagonized by a sub-effective dose of MK-801. These results suggest that EEPV would be useful for treating cognitive impairments induced by cholinergic dysfunction, and that it exerts its effects via NMDA receptor signaling.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 03/2010; 48(6):1671-6. · 2.99 Impact Factor
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    ABSTRACT: The aim of this study was to determine the mechanism underlying the neuroprotective effects of the ethanolic extract of the seeds of Cassia obtusifolia (COE) (10 or 50mg/kg/day, p.o) on transient cerebral global ischemia induced by bilateral common carotid artery occlusion (2VO) in mice. Immunohistochemical and western blot studies showed that levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the hippocampal CA1 region at 1day post-2VO were attenuated by COE (50mg/kg/day, p.o), which was administered immediately after 2VO. Furthermore, OX-42 - and glial fibrillary acidic protein (GFAP)-positive cell numbers at 4 days post-2VO were markedly attenuated by COE (50mg/kg/day, p.o) treatment for 4 days in CA1. Viable neurons detected by Nissl at 7 days post-2VO were increased by administering COE (50mg/kg/day, p.o) for 7 days. In addition, COE increased the expressions of phosphorylated cAMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in CA1 in naïve-control within 1 and 6h, respectively, and these expressions were also profoundly increased in 2VO-treated mice by COE at immediately post-2VO. These results suggest that the neuroprotective effects of COE are due to its anti-inflammatory effects and to its upregulation of BDNF expression and CREB phosphorylation.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2009; 47(7):1473-9. · 2.99 Impact Factor
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    ABSTRACT: A novel SLM (spatial light modulator), named SOM (spatial optical modulator) has been developed. SOM is one dimensional mirror array device, so the pixel number and the dimension of the mirror array could be easily designed for application specific. Full-HD rear projection displays with 1080-pixel SOM devices and VGA resolution embedded mobile projection displays with 480-pixel SOM devices have been developed. SOM device packaging was designed, characterized and fabricated for high resolution and high quality displays. Fine-pitch interconnections as well as submount fabrication, hermetic sealing, PCB bonding, wire bonding and bond wire passivation processes were designed and accomplished. The dimension of the packaged SOM chip modules were 27.4times68.3times4.6 mm<sup>3</sup> and 13.4times12.0times3.1 mm<sup>3</sup> for RPTV(rear projection tele-vision) and pico-projection modules, respectively. The mechanical, electrical, thermal and optical characteristics like as bending, thermal distribution and its uniformity, electrical noise characteristics were controlled.
    Electronic Components and Technology Conference, 2008. ECTC 2008. 58th; 06/2008