• 대한수의학회지
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• 제39권3호
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• pp.538-544
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• 1999

To elucidate the involvement of interleukin-$1{\beta}$ converting enzyme (ICE) in the course of experimental autoimmune encephalomyelitis (EAE), we induced EAE by immunizing rats with an emulsion of rat spinal cord homogenate with complete Freund's adjuvant supplemented with Mycobacterium tuberculosis (H37Ra, 5mg/ml) and then examined the expression of ICE in the spinal cord of rats with EAE. In normal rat spinal cords, ICE is constitutively, but weakly, expressed in ependymal cells, neurons, and some neuroglial cells. In EAE, many inflammatory cells are positive for ICE, and the majority of ICE+ cells were identified as ED1+ macrophages. During this stage of EAE, the number of ICE+ cells in brain cells, including neurons and astrocytes, increased and these cells also had increased ICE immunoreactivity. These findings suggest that the upregulation of ICE in both brain cells and invading hematogenous cells is stimulated by a secretory product from inflammatory cells, and that this enzyme is involved in the pathogenesis of EAE via the production of IL-1 beta.

• Advances in Traditional Medicine
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• 제4권3호
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• pp.211-214
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• 2004

The inhibitory effect of dl-puerol A as but-2-enolide isolated from Sophora japonica was investigated on copper ion-induced protein oxidative modification in vitro. It inhibited copper-induced protein oxidative modification. However, its inhibitory effect was a little weaker than that of $dl-{\alpha}-tocopherol$ as an antioxidant. The results demonstrated that dl-puerol A, one of but-2-enolides, might be of use in the oxidative stress.

• Bulletin of the Korean Chemical Society
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• 제31권6호
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• pp.1609-1614
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• 2010

Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Standard in vitro test was chosen using a rat brain homogenate as the source of AChE. Screening of reactivation potency was performed with two concentration of reactivator (1000 ${\mu}M$ and 10 ${\mu}M$). Results were compared to established reactivators pralidoxime, methoxime, HI-6, trimedoxime and obidoxime. More than 30 novel reactivators performed equal or better reactivation ability of POX-inhibited AChE compared to currently used reactivators. The structure-activity relationship for reactivators of paraoxon-inhibited AChE was developed.

• Natural Product Sciences
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• 제8권4호
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• pp.129-132
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• 2002

The MeOH extract of the twig of Morus alba L. (Moraceae) inhibited strong lipid peroxidation activity. In order to find out active principle from the plant, acivity-guided fractionation was performed and five antioxidant compounds were isolated. Their chemical structures were identified as 6-geranylapigenin (1), 6-geranylnorartocarpetin (2), resveratrol (3), oxyresveratrol (4) and quercetin (5) by physicochemical and spectrometric methods. Compounds 1-5 significantly inhibited lipid peroxidation in rat brain homogenate $(IC_{50}\;values\;of\;3.37,\;3.74,\;0.23,\;0.29\;and\;0.06\; {\mu}M,\;respectively)$.

• 대한약리학회지
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• 제23권2호
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• pp.101-111
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• 1987

중추신경계 특히 뇌내(腦內)의 무수카린성 콜린 수용체 (mAchR)에 대한 수용체 특성의 연구의 하나로, 물리 화학적 성상에 다른 두 종류의 콜린길항제를 사용하여 서로 다른 두 형태의 조직에서 약물의 작용양상 및 다른 약물과의 상호작용을 정초하였다. 실험동물로는 흰쥐를 일정기간 규정사료를 사육하였고, 사용한 Radioactive ligands는 $(^3H)$ QNB와 $(^3H)$ NMS였으며 그외에 다른 수종의 길항제 또는 효능제와의 치환작용을 brain homogenates와 intact brain cell aggregates에서 관찰하여 다음과 같은 결과를 얻었다. 1. $(^3H)$ QNB와 $(^3H)$ NMS는 모두 질량작용의 법칙에 비례하여 수용체와의 결합에서 높은 친화력과 포화를 보였으며 또한 높은 결합 능력을 나타내었다. 더욱이 homogenates 제제와 intact cell aggregates제제에서의 결과 사이에는 유사한 점이 많았다. 2. Homogenates제제를 사용한 실험에서, 제 3 급아민콜린길항제인 QNB, atropine과 scopolamine 또는 제 4 급 암모늄골린 길항제인 methylatropine과 methylscopolamine을 사용하여 위의 radioactive ligands와의 치환작용을 검토하였다. $(^3H)$ NMS 실험군에서는 제 3 급아민 및 제 4 급 암모늄길항제 모두가 구조의 구별없이 질량작용의 법칙에 따라 치환되었으나 $(^3H)$ QNB 실험군에서는 제 4급 암모늄콜린 길항제들을 단일성(unity)이 아닌 높고 낮은 두 종류의 친화도를 가진 결합부위의 양상을 나타내었다. 또 비특이성 콜린길항제인 pirenzepine을 사용한 실험군에서는 두 ligands을 모두 치환시켰고 서로 다른 결합부위가 있음을 보였다. 3. Intact cell aggregates 제제를 사용한 실험에서, $(^3H)$ NMS와 $(^3H)$ QNB 모두 homogenates 제제에서와 같은 양상의 반응을 보였다. 또 $(^3H)$ NMS를 radioligand로 하여 수종의 콜린길항제와 수종의 콜린 효능제를 사용하여 약물 상호작용으로 수용체의 성질을 검토하였다. 그 결과 콜린 길항제들은 질량작용의 법칙에 따라 치환되었으나 콜린 효능제 투여군에서는 높고 낮은 두 종류의 다른 친화력의 결항부위를 나타내었다. 4. 위의 실험의 결과로,(a) 친유성콜린 길항제인 $(^3H)$ QNB는 친수성 콜린길항제인 $(^3H)$ NMS보다 훨씬 높은 결합능력을 보였으며 이것으로 수용체 특히 mAchR의 존재 장소 또는 mAchR의 형상의 일부는 세포막 표면 뿐 아니라 세포막내의 어떤 부위와도 관계가 되는 것으로 간주되는데 이것이 $(^3H)$ QNB가 $(^3H)$ NMS보다 높은 최대 결합능력 $(B_{max})$을 나타낼 이유이다. (b) 두 종류의 다른 제제에서 우리는 같은 양상의 결과를 관찰하었기에 결점이 많은 homogenates 제제보다는 intact cell aggregates 제제를 수용체 연구에 대한 새로운 실험모형(experiment model)으로 사용할 수 있는 가능성을 제시하고자 한다.

• Journal of Nutrition and Health
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• 제17권4호
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• pp.313-319
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• 1984

몰핀의 투여량, 몰핀을 주사하는 시간, 쥐의 나이에 따라서 몰핀이 food intake에 미치는 효과 유무를 Sprague-Dawley 쥐를 이용해 조사하였다. 또한 $^{3}H-naloxone$을 이용한 opiate receptor binding assay에 의해서 정상상태에서 몰핀이나 식염수를 주사한 쥐의 뇌에서 opiate receptor binding의 변화를 조사하여 아래와 같은 결과를 얻었다. Food intake에 미치는 몰핀의 효과는 2시간에 유의차를 나타냈으며 몰핀 투여량이 증가할수록 효과는 감소한 것으로 나타났다. 또 어릴수록 효과가 많이 나타났으며 female이 male보다 효과가 컸으나 지속적이지 못했다. 몰핀을 주사하는 시간을 달리하는 실험에서 male 이나 female 모두 10:00에 주사한 경우에 몰핀 효과가 16 : 00에 주사한 경우보다 크게 나타났다. Opiate receptor binding assay 결과, 몰핀을 주사한 쥐에서 $^{3}H$ naloxone binding 이 유의있게 감소했으며 오전에 몰핀을 주사한 쥐에서 naloxone binding 이 더 많이 감소한 것으로 나타났다. 이상의 실험에서, 몰핀이 food intake 에 미치는 효과는 몰핀의 opiate receptor binding을 통해서 작용한 것으로 생각된다.

• BMB Reports
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• 제30권6호
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• pp.443-447
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• 1997

We have developed a novel method for assays of spermidine and spermine synthase (aminopropyltransferase) activities using antibody against 5'-deoxy-5'-methylthioadenosine (MTA). A new assay is reported here which is based on the observation that MTA is formed as a stoichiometric by-product of the spermidine and spermine synthases reactions. In order to determine MTA, a radioimmunoassay method with sensitivity and rapidity was used. (Lee and Cho, 1997). In this assay, adenine must be added in the reaction mixture, since it effectively inhibits the action of MTA phosphorylase by which MTA is metabolized. This assay is a improvement in term of sensitivity and time saving, compared to the currently used methods. It has a level of sensitivity (100 fmol) sufficient to monitor aminopropyltransferase activities in incubations containing as little as $10{\mu}g$ protein prepared from rat tissue homogenate. The results obtained showed that this method is particularly useful for cultured cells with low enzyme concentration. Moreover, this assay has the advantage which allows studies using alternative substrates (other amines). Spermidine synthase activity was high in rat liver, but low in rat kidney. The activity of spermine synthase was in most rat tissues very low as compared to that of spermidine synthase, but was high in brain.

• The Korean Journal of Physiology and Pharmacology
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• 제2권5호
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• pp.565-572
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• 1998

The present study was to evaluate the protective effects of bromocriptine, which is known as $D_2$ dopamine receptor agonist and used for the treatment of patients with Parkinson's disease (PD), on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro and in vivo. Lipid peroxidation product (malondialdehyde; MDA) produced by the administration of 6-OHDA was profoundly reduced following the treatment of bromocriptine in a dose-dependent manner in rabbit brain homogenate. Quinone formation by 6-OHDA autoxidation was also attenuated, and its effect was as potent as other antioxidants. Pretreatment of bromocriptine reduced the cytotoxicity of 6-OHDA on SH-SY5Y neuroblastoma cell lines dose-dependently. The loss of striatal dopamine and its metabolite, DOPAC (dihydroxyphenylacetic acid) as well as increase of MDA production caused by intrastriatal injection of 6-OHDA was significantly recovered following the treatment of bromocriptine. The present study clearly showed that bromocriptine had a protective action against 6-OHDA-induced neurotoxicity. These results suggest that bromocriptine has the antioxidant properties, which could be another advantage for delaying the progress of Parkinson's disease.

• Toxicological Research
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• 제24권3호
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• pp.169-174
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• 2008

This study examined the mechanisms underlying the effects of the vasorelaxation active substance(VAS), dimethyladenosine-5'-L-arabinose, and its partial purification fraction on nitric oxide synthase in improving erectile dysfunction with particular focus on the nitric oxide (NO)-cGMP pathways. Two rat models, 9-month-old SD rats and 11-month-old SD rats, were given VAS(40 mg/kg per day) for 4 days, The aqueous fraction of silworm male pupae extract; semi-purified VAS(100 mg/kg per day) for 10 days, respectively. The NOS activities of the following three enzymes were examined: neuronal NO synthase(nNOS), inducible NOS(iNOS), endothelial NOS(eNOS), vascular endothelial growth factor on endothelial cells(VEGF) and anti-inflammation effect of Tumor necrosis factor-$\alpha$. The results showed increases in the nitric oxide synthase activities. Western blotting of the tissue homogenate showed an increase in the nNOS level in the brain and tongue, and an increase in the endothelial NO synthase(eNOS) level in penis. However, there was little association with VEGF production in HUVEC endothelial cells and no relationship with TNF-$\alpha$ which showed low levels.

• Biomolecules & Therapeutics
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• 제12권3호
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• pp.138-144
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• 2004

Therapeutic effect of a Kampo medicine, Choto-san, in patients with vascular dementia was demonstrated by a double-blind and placebo-controlled clinical trial. To clarify the therapeutic efficacy of Choto-san, anti-ischemic effect in mice, hypotensive effect in spontaneously hypertensive rats (SHR), anti-oxidative effects in vitro, and N-methyl-D-aspartate (NMDA) receptor-blocking activity using Xenopus oocytes were studied. (1) Pretreatment with Choto-san (0.75-6.O g/kg, P.O.) or a component herb Chotoko (Uncaria genus: 75 - 600 mg/kg, P.O.) prevented ischemia-induced impairment of spatial learning behaviour in mice. Indole alkaloids- and phenolic fractions extracted from Chotoko also improved significantly the learning deficit. (2) Subchronic administration of Choto-san (0.5 g/kg, p.o.) caused a significant hypotensive effects in SHR. (3) Choto-san, Chotoko, and the phenolic constituent, (-) epicatechin, significantly protected the NG108-15 cell injury induced by $H_20_2$ exposure in vitro and also inhibited lipid peroxidation in the brain homogenate. (4) Indole alkaloids, rhynchophylline and isorhynchophylline (1-100 uM), reversibly reduced NMDA-induced current in the receptor-expressed Xenopus oocytes. These results suggest that anti-vascular dementia effects of Choto-san are mainly due to the effect of Chotoko. From these results, it is possible to make a novel dietary supplement through several extraction steps from Chotoko.