• 한국식품위생안전성학회지
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• 제5권1호
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• pp.7-12
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• 1990

Radiolabeled Brazilin(^3H-Brazilin)을 웅성 Wistar Rats에 투여하여 plasma concentration-time profile, urine 및 bile로의 배설, 조직분포 및 plasma protein에 대한 결합률을 살펴보았다. 1. Pharmacokinetic parameters는 다음과 같았다. $t_{1/2}$은 13.7 hr, AUC는 $\53.38\;\mu\textrm{g}{\cdot}hr/ml$, AUMC는 $1013.4\;\mu\textrm{g}{\cdot}hr^2/ml$ MRT는 18.95hr, Vss 17.778l/kg 그리고 CL은 936.77ml/hr.kg였다. 2. Plasma concentration-time profile에서 enterohepaic circulation을 시사하여 2nd peak가 발견되었고. 담즙배설 실험으로 확증할 수가 있었다. 결구투여 후 담즙 배설은 투여량의 64.4%가 10시간에 걸쳐 배설되었고, 3시간째 그 배설속도는 maximum을 이뤘다. 3. Vss는 17.8 l/kg으로 큰 값을 나타냈고, 따라서 뇌를 제외한 대부분의 조직에 Brazilin은 분포하였고 특히 liver와 kidney, epididymus 그리고 testis에 고농도 분포함을 알 수 있었다. 4. 경구투여량의 44.1%가 , 정맥주사 후 투여량의 62.9%가 urine을 통해 배설되었다. Urine을 통해 배설되는 양의 대부분(80%)은 24시간 내에 배설되었다. 5. Plasma protein에 대한 결합율을 한외여과법으로 측정한 결과 $40{\pm}4%$가 결합하는 것으로 나타났다.

• 생명과학회지
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• 제21권7호
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• pp.985-991
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• 2011

본 연구는 고지방식이로 인한 비만으로 불균형된 지질구성과 산화적 손상이 신경세포형성과 초기발현단백질에 미치는 생물학적 영향을 알아보고, 규칙적인 운동의 효과를 알아보기 위하여 실시하였다. 실험동물은 4주령 SD rat 수컷 30마리를 1주간의 적응기간을 둔 뒤, 15주간 고지방식이를 통해 비만으로 유도하였으며, high fat diet sedentary (HDS, n=15)와 high fat diet and training (HDT, n=15)으로 분류하여 연구하였다. 운동강도는 1~4주는 저강도, 5~8주는 중강도로 주5회 실시하였다. 8주 트레이닝 후 혈청지질, 8-OHdG, MDA, neurotrophic factor, 그리고 IEG를 분석하였다. 그 결과 TC와 TG에서 HDS와 HDT 사이 유의한 차이가 나타났다(p<0.05). 8-OHdG에서 HDT는 트레드밀 트레이닝 후에 HDS보다 낮게 나타났다(p<0.05). 해마에서 c-jun, BDNF 그리고 간에서 MDA의 단백질 발현은 HDT가 트레드밀 트레이닝 후 HDS보다 높게 나타났다(p<0.05). 결론적으로 8주간 트레드밀 훈련은 고지방식이 비만 유도 쥐의 혈청지질 성분의 불균형을 개선시키고, 조직과 혈청의 산화적 손상과 DNA 손상을 완화시켜 주어, 비만으로 인한 합병증 예방에 도움을 줄 수 있을 것으로 사료된다. 또한 NT의 발현을 증가시킴으로써 손상된 뇌기능과 신경세포의 생성 기전 활동에 긍정적 영향을 나타냄으로써 공간적 학습기능의 향상을 가져온 것으로 판단된다.

• Advances in Traditional Medicine
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• 제5권3호
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• pp.216-230
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• 2005

Although the field of study in immune enhancing compounds is relatively new, natural products from plants represent a rich and promising source of novel molecules with immunomodulating properties, Microglial cells, the main immune effector cells of the brain, usually display a ramified morphology and low expression levels of immunologically relevant antigens such as MHC class I and class II. Since any compound which participates in activation of phagocytic cells contributes to the production of potentially toxic factors, the search for convenient in vitro test-systems and study of mechanisms of action of these agents are of great interest. Human blood polymorphonuclear (PMN) cells and primary microglial cells isolated from Sprague-Dawley rats were used as cellular screening tests for study of phagocytosis-stimulating action of immunomodulating agents. Numbers of phagocytic activity were evaluated by the phagocyte ingestion of yeast cells and NO-synthase activity, nitrite production, and nitroblue tetrazolium test were determined after phagocyte stimulation. It was possible to demonstrate that indexes of phagocytic activity can be used as quantitative indicators for measurement immunomodulating activity. As a positive control, Zymosan A-induced phagocytosis in both PMN cells and primary microglial cells was used. $IFN-{\gamma}$ (0.1 -1 U/ml) stimulated phagocytosis in PMN cells 1.2 times after 2 - 3 h incubation, although at higher concentrations (10 - 100 U/ml) it strongly inhibited phagocytosis. In a similar way, at higher concentrations, $IFN-{\gamma}$ (100 - 500 U/ml) suppressed phagocytosis in zymosan-A stimulated microglial cells. When Polypodium leucotomus, cambricum and vulgare extracts were tested alone, increased levels of phagocytosis were observed in PMN. In addition, microglial cells showed both increased phagocytosis and MHC class-II antigen expressions. Surprisingly, when PMN and microglia were treated with a combination of Polypodium and $IFN-{\gamma}$, phagocytosis was not inhibited. We did not find changes in NO-synthase activity and nitrite production in both microglia and PMN cells activated by different immunomodulating agents. These results indicate that primary microglial cell cultures as well as human PMN cells can provide reproducible quantitative results in screening phagocytic activity of different immunoactive compounds. Furthermore, both inhibitory or activation mechanisms might be studied using these in vitro experimental approaches.

• Archives of Pharmacal Research
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• 제28권3호
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• pp.335-342
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• 2005

The effects of ginsenosides Rg$_3$(R) , Rg$_3$(S) and Rg$_5$/Rk$_1$ (a mixture of Rg$_5$ and Rk$_1$ 1:1, w/w), which are components isolated from processed Panax ginseng C.A. Meyer (Araliaceae), on memory dysfunction were examined in mice using a passive avoidance test. The ginsenosides Rg3(R), Rg3(S) or Rg$_5$/Rk$_1$, when orally administered for 4 days, significantly ameliorated the memory impairment induced by the single oral administration of ethanol. The memory impairment induced by the intraperitoneal injection of scopolamine was also significantly recovered by ginsenosides Rg3(S) and Rg$_5$/Rk$_1$. Among the three ginsenosides tested in this study, Rg$_5$/Rk$_1$ enhanced the memory function of mice most effectively in both the ethanol­and scopolamine-induced amnesia models. Moreover, the latency period of the Rg$_5$/Rk$_1$­treated mice was 1.2 times longer than that of the control (no amnesia) group in both models, implying that Rg$_5$/Rk$_1$ may also exert beneficial effects in the normal brain. We also evaluated the effects of these ginsenosides on the excitotoxic and oxidative stress-induced neuronal cell damage in primary cultured rat cortical cells. The excitotoxicity induced by glutamate or N­methyl-D-aspartate (NMDA) was dramatically inhibited by the three ginsenosides. Rg$_3$(S) and Rg$_5$/Rk$_1$ exhibited a more potent inhibition of excitotoxicity than did Rg$_3$(R). In contrast, these ginsenosides were all ineffective against the H$_2$O$_2$- or xanthine/xanthine oxidase-induced oxidative neuronal damage. Taken together, these results indicate that ginsenosides Rg$_3$(S) and Rg$_5$/Rk$_1$ significantly reversed the memory dysfunction induced by ethanol or scopolamine, and their neuroprotective actions against excitotoxicity may be attributed to their memory enhancing effects.

• 한국결정학회:학술대회논문집
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• 한국결정학회 2003년도 춘계학술연구발표회
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• pp.18-18
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• 2003

Thioredoxin (Trx) is a small redox protein that is ubiquitously distributed from achaes to human. In diverse organisms, the protein is involved in various physiological roles by acting as electron donor and regulators of transcription and apoptosis as well as antioxidants. Sequences of Trx within various species are 27～69% identical to that of E. coli and all Trx proteins have the same overall fold, which consists of central five β strands surrounded by four α helices. The N-terminal cysteine in WCGPC motif of Trx is redox sensitive and the motif is highly conserved. Compared with general cysteine, the N-terminal cysteine has low pKa value. The result leads to increased reduction activity of protein. Recently, novel thio.edoxin-related protein (TRP14) was found from rat brain. TRP14 acts as disulfide reductase like Trx1, and its redox potential and pKa are similar to those of Trx1. However, TRP14 takes up electrons from cytosolic thioredoxin reductase (TrxR1), not from the mitochondrial thioredoxin reductase (TrxR2). Biological roles of TES14 were reported to be involved in regulating TNF-α induced signaling pathways in different manner with Trx1. In depletion experiments, depletion of TRP14 increased TNF-α induced phosphorylation and degradation of IκBα more than the depletion Trx1 did. It also facilitated activation of JNK and p38 MAP kinase induced by TNF-α. Unlike Trx1, TRP14 shows neither interaction nor interference with ASK1. Here, we determined three-dimensional crystal structure of TRP14 by MAD method at 1.8Å. The structure reveals that the conserved cis-Pro (Pro90) and active site-W-C-X-X-C motif, which may be involved in substrate recognition similar to Trx1 , are located at the beginning position of strand β4 and helix α2, respectively. The TRP14 structure also shows that surface of TRP14 in the vicinity of the active site, which is surrounded by an extended flexible loop and an additional short a helix, is different from that of Trx1. In addition, the structure exhibits that TRP14 interact with a distinct target proteins compared with Trx1 and the binding may depend mainly on hydrophobic and charge interactions. Consequently, the structure supports biological data that the TRP14 is involved in regulating TNF-α induced signaling pathways in different manner with Trx1.

• 생명과학회지
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• 제17권7호통권87호
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• pp.1019-1022
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• 2007

뇌졸중 환자에 사용되는 tPA치료법은 혈전을 용해시키고 혈액의 흐름을 용이하게 해 주기 때문에 매우 중요하게 사용되고 있다. 동물 실험모델을 이용한 이전의 실험결과에 따르면 tPA뿐 아니라 tPA의 일종인 pamite-plase 역시 30분 이내 탁월한 혈전 용해의 효과를 보여주었다. 그러나 fPA치료법은 단시간 처리와 출혈, 부종과 같은 여러 가지 부작용이 수반될 수 있으며 이들은 MMP-9의 활성 조절과 깊은 관련이 있는 것으로 보고되고 있다. 본 연구에서는 임상에 사용되는 tPA의 한 종류인 alteplase와 이러한 부정적인 효과를 극복하기 위해 개발된 pamiteplase의 MMP-9활성에 미치는 효과를 비교 분석하였다. 랫트의 뇌로부터 추출한 신경세포에서 alteplase의 처리는 농도의존적으로 MMP-9의 발현을 촉진시켰고 활성화된 형태의 MMP-2역시 증가되는 양상을 보였다. 반면, pamiteplase의 경우 MMP-2와 MMP-9의 발현양상에 영항을 미치지 않았다. 유사한 효과는 뇌신경계를 구성하는 다른 세포인 성상세포에서도 관찰되었다. 즉 대뇌의 성상세포를 분리, 배양하여 이들의 효과를 확인한 결과 신경세포에서와 마찬가지로 alteplase의 경우 농도의존적으로 증가하였고 pamiteplasse의 경우 변화를 나타내지 않았다. Pamiteplase는 뇌신경구성세포에서 출혈과 부종을 유도하는 데 관련이 있는 것으로 보고된 MMP-9의 활성에 영향을 미치지 않는 것으로 보아 alteplase에 비해 보다 효과적인 치료제로서의 가능성을 보여주고 있다.

• 전자공학회논문지SC
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• 제48권4호
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• pp.1-9
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• 2011

쇼크(shock)란 조직에 필요한 산소 요구량과 공급 간의 불균형에 의해 유발되는 임상증후군을 말한다. 환자의 치료효과와 생존율 향상을 위해서 쇼크의 조기 진단은 매우 중요하다. 그러나 현재 쇼크 진단에 사용되는 맥박, 혈압 등 생체 징후의 경우 출혈 정도를 제대로 반영하지 못하여 환자에 대한 처치가 늦어질 수 있다. 따라서 쇼크의 조기 진단을 위한 많은 연구들이 진행되어 왔으며, 조직의 저산소증, 대사성 산증을 반영해주는 지표인 젖산 농도와 관류 측정의 유용성이 입증된 바 있다. 본 연구에서는 흰쥐를 대상으로 정량적 출혈을 유도한 후, 젖산 농도 측정과 laser Doppler flowmeter를 통해 관류를 측정하였으며, 지혈 후 젖산 농도/관류의 비(ratio)를 생존 예측을 위한 새로운 지표로써 제안하였다. 새로 제안된 지표를 통한 생존예측을 ROC 커브 방법에 적용한 결과, 민감도 90.0%, 특이도 96.7%, 정확도 94.0%를 보였으며, 생존군과 사망군 간 새로운 지표의 유의한 차이도 가장 조기에 보여주었다. 향후 임상 적용 연구를 통해 새롭게 제안한 지표의 임상 적용이 가능하다면, 쇼크 환자를 조기 진단하고 치료효과를 높일 수 있을 것으로 생각된다.

• 대한약침학회지
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• 제7권1호
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• pp.53-61
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• 2004

Substantial evidence suggests that behavioral and reinforcing effects of cocaine can be mediated by the mesolimbic dopaminergic system. It has been shown that repeated injections of cocaine produce increase in locomotor activity, expression of the immediate-early gene, c-fos in the nucleus accumbens (NAc), which was one of the main dopaminergic terminal areas. Herbal-acupuncture as a therapeutic intervention has been widely used for the treatment of many functional disorders such as drug abuse. Coptidis Rhizoma (CR) and its main component, berberine (BER) were selected as herbal medicine of herbal-acupuncture. Both medicines have been known to have the therapeutic effect on the central nervous system. In order to investigate the effects of CR and BER herbalacupuncture at shenmen (HT7) point (CR/H and BER/H) on the cocaine-induced behavioral sensitization, the influence of CR/H and BER/H on repeated cocaine-induced locomotor activity, the change of c-Fos expression in the brain by immunohistochemistry were examined. Male SD rats were given CR/H (0.4mg/kg) and BER/H (0.1mg/kg) 30 min before daily injections of cocaine hydrochloride (15mg/kg. i.p.) 10 days. After 3 days withdrawal, rats received a challenge injection of cocaine (15mg/kg, i.p.). Systemic challenge with cocaine produced much larger increased locomotor activity, accumbal Fos-like immunoreactivity in the NAc. Pretreatment with CR/H and BER/H significantly inhibited cocaine-induced locomotor activity, the change of c-Fos expression in the rats. Our data demonstrated that the inhibitory effects of cocaine-induced behavioral sensitization by CR/H and BER/H were closely associated with the reduction of presynaptic dopamine release in the NAc. These results suggest that CR/H and BER/H can be effectively applied to cocaine addiction.

• The Korean Journal of Physiology and Pharmacology
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• 제19권4호
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• pp.309-318
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• 2015

Alcohol consumption increases the risk of type 2 diabetes. However, its effects on prediabetes or early diabetes have not been studied. We investigated endoplasmic reticulum (ER) stress in the pancreas and liver resulting from chronic alcohol consumption in the prediabetes and early stages of diabetes. We separated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 diabetic animal model, into two groups based on diabetic stage: prediabetes and early diabetes were defined as occurrence between the ages of 11 to 16 weeks and 17 to 22 weeks, respectively. The experimental group received an ethanol-containing liquid diet for 6 weeks. An intraperitoneal glucose tolerance test was conducted after 16 and 22 weeks for the prediabetic and early diabetes groups, respectively. There were no significant differences in body weight between the control and ethanol groups. Fasting and 120-min glucose levels were lower and higher, respectively, in the ethanol group than in the control group. In prediabetes rats, alcohol induced significant expression of ER stress markers in the pancreas; however, alcohol did not affect the liver. In early diabetes rats, alcohol significantly increased most ER stress-marker levels in both the pancreas and liver. These results indicate that chronic alcohol consumption increased the risk of diabetes in prediabetic and early diabetic OLETF rats; the pancreas was more susceptible to damage than was the liver in the early diabetic stages, and the adaptive and proapoptotic pathway of ER stress may play key roles in the development and progression of diabetes affected by chronic alcohol ingestion.

• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.245-251
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• 2008

Single-channel recordings of TASK-1 and TASK-3, members of two-pore domain $K^+$ channel family, have not yet been reported in dorsal root ganglion (DRG) neurons, even though their mRNA and activity in whole-cell currents have been detected in these neurons. Here, we report single-channel kinetics of the TASK-3-like $K^+$ channel in DRG neurons and up-regulation of TASK-3 mRNA expression in tissues isolated from animals with spinal cord injury (SCI). In DRG neurons, the single-channel conductance of TASK-3-like $K^+$ channel was $33.0{\pm}0.1$ pS at - 60 mV, and TASK-3 activity fell by $65{\pm}5%$ when the extracellular pH was changed from 7.3 to 6.3, indicating that the DRG $K^+$ channel is similar to cloned TASK-3 channel. TASK-3 mRNA and protein levels in brain, spinal cord, and DRG were significantly higher in injured animals than in sham-operated ones. These results indicate that TASK-3 channels are expressed and functional in DRG neurons and the expression level is up-regulated following SCI, and suggest that TASK-3 channel could act as a potential background $K^+$ channel under SCI-induced acidic condition.