• 한국해양바이오학회지
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• 제1권3호
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• pp.213-217
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• 2006

본 연구는 황백에 함유되어 있는 주요 화합물인 berberine, palmatine, limonin 및 rutaecarpine의 CYP2D6 및 p-glycoprotein 활성에 대한 저해정도를 탐색함으로써, 황백을 다른 양약과 병용시 약물상호작용을 유발할 수 있는 가능성을 평가하고자 하였다. 인체 간 마이크로좀 시료에 CYP2D6 동효소의 기질약물인 dextromethorphan과 NADPH 재생성계 및 저해제 ($200{\mu}M$)를 첨가한 후 반응시켜 생성된 대사물을 LC/MS/MS를 이용하여 정량하여 CYP2D6 동효소 활성의 변화를 평가하였다. 또한 약물수송단백인 p-glycoprotein의 활성은 L-MDR1 세포주를 이용한 calcein AM 축적 실험을 통하여 평가하였다. 그 결과 식물 알카로이드인 berberine에서 강력한 CYP2D6 활성 저해능을 관찰하였으며, 저해 효과는 농도 의존적으로 증가하였으며, mechanism-based 저해 기전을 나타내었다. 그러나 limonine과 rutaecarpine은 CYP2D6 저해 활성을 보이지 않았고, p-glycoprotein 기능에 대해서는 평가한 어떤 화합물도 저해 활성을 나타내지 않았다. 황백의 주요 성분인 berberine의 CYP2D6 활성 저해능을 고려할 때, 황백을 CYP2D6 기질약제와 병용시 약물상호작용을 유발할 가능성을 보여준다. 이러한 황백의 CYP2D6를 매개로한 임상적인 약물상호작용 가능성은 임상시험을 통하여 추가적인 검정이 필요할 것으로 사료된다.

• 동의생리병리학회지
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• 제18권2호
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• pp.451-456
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• 2004

Based on the data from our previous studies, four new diabetic remedies were composed with the addition of Coicis Semen into Okchun-san (OCH), Commelinae Herba into Gangsim-tang (GST) , Scrophulariae Radix into Sunki-san (SKS), and Erythrinae Cortex into Yukmijihuang-hwan (YMG). The water extracts of these new remedies were treated in 3T3-L1 fibroblasts and adipocytes in order to investigate insulin-like substances and insulin sensitizers, respectively. With and without differentiation inducers, unmodified SKS (SKS-O) treatment induced 3T3-L1 fibroblasts into adipocytes more than the control. However, without inducers, YMG treatment, but not SKS, induced the differentiation more than the control among modified remedies. Without inducers, SKS, OCH as well as YMG increased the induction of differentiation from 3T3-L1 fibroblasts into adipocytes, compared to the control. The treatment of OCH and YMG with 1 ng/mL insulin increased glucose uptake much more than only insulin 1 ng/mL treatment. Thus, OCH and YMG contained increased insulin actions. In conclusions, the modified remedies, OCH and YMG, contained insulin-like substances and insulin sensitizers, and they can be improved the hypoglycemic effects.

• Biomolecules & Therapeutics
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• 제11권3호
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• pp.174-177
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• 2003

The present experiment was performed to investigate the protective effects of paeonol isolated from Moutan Cortex Radicis on primary cultured rat hepatocytes exposed to Br-A23187 ($Ca^{2+}$ ionophore). Br-A23187 is frequently used as a model of cell killing as inducing both necrotic and apoptotic cell death. Hepatocytes were isolated by collagenase perfusion from livers of fasted male Sprague Dawley rats and cultured overnight. Cell viability was determined by propidium iodide using fluorocytometry in Krebs-Ringer-HEPES buffer at pH 7.4. In addition, intracellular calcium was measured by excitation at 340 and 380 nm and emission at 505 nm using a luminescence spectrophotometer. Paeonol (20-100 ${\mu}M$) inhibited cell killing induced by 10 ${\mu}M$ Br-A23187, in a dose-dependent manner. Paeonol also reduced increased intracellular calcium level when hepatocytes were exposed to Br-A23187. Therefore, the present results suggest that paeonol protects the hepatocytotoxicity induced by Br-A23187, via inhibiting the influx of calcium into into rat hepatocytes.

• The Korean Journal of Physiology and Pharmacology
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• 제9권3호
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• pp.159-164
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• 2005

Effects of antioxidants on the established nephropathy were investigated. The experimental nephropathy was induced in rats by intravenous injection of adriamycin (2 mg/kg). Six weeks later, when proteinuria was apparent, the rats were supplemented with N-acetylcysteine (NAC, 1 g/kg/day) in drinking water for additional 6 weeks. Glomerulosclerosis score and tubulointerstitial injury index were determined by light microscopy. Expression of transforming growth factor (TGF) ${\beta}1$ and laminin ${\beta}1$ was determined in the renal cortex by reverse transcription-polymerase chain reaction, Western blotting, immunohistochemistry, and immunogold electron microscopy. The adriamycin-induced proteinuria as well as the glomerulosclerosis and tubulointerstitial injury was ameliorated by the treatment with NAC. Adriamycin increased the expression of TGF ${\beta}1$ mRNA and protein, which was ameliorated by NAC. Although the expression of laminin ${\beta}1$ mRNA was increased, adriamycin did not significantly alter that of its protein. These results indicate that antioxidants ameliorate the established nephropathy in association with normalization of overexpressed TGF ${\beta}1$.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.86-86
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• 2001

Based on the potential inhibitors of cyclooxygenase-2 (COX-2) as anti-inflammatory or cancer chemopreventive agents, we have evaluated the active principles of COX-2 inhibition from natural products. The methanol extract of the cortex of Eugenia caryoplyllata (Myrtaceae) showed the potent inhibition of prostaglandin E$_2$(PGE$_2$) production in lipopolysaccharide (LPS)-activated RAW 264.7 cells (98.3% inhibition at the test concentration of 10 $\mu\textrm{g}$/$m\ell$) Further, hexane-soluble layer was the most active partition compared to ethyl acetate, n-butanol, and water -soluble parts. By bioassay-guided fractionation of hexane-soluble layer, eugenol was isolated and exhibited a significant suppression of PGE$_2$ production (IC$\_$50/=0.06$\mu\textrm{g}$/$m\ell$). In addition, eugenol suppressed the COX-2 gene expression in LPS-stimulated mouse macrop-hage cells. Therfore, eugenol might be a plausible lead candidate for further developing the COX-2 inhibitor as an anti-inflammatory or cancer chemopreventive agent.

• Journal of Nutrition and Health
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• 제34권1호
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• pp.14-22
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• 2001

In this study, we examined the effects of dietary fatty acids and vitamin E supplementation on antioxidant systems in the rat brain regions. The Sprague Dawley rats were fed the experimental diets 3-4 wks prior to the conception. Experimental diet consisted of 10% fat(wt/wt) which were safflower oil(SO, poor in $\omega$3 fatty acids), mixed oil(MO, P/M/S ratio=1.03:1.45:1,$\omega$6/$\omega$3 ratio=6.3) and mixed oil supplemented with vitamin E(ME:MO+500mg vitamin E/kg diet). At 3 and 9 weeks of age of the newborn rats, frontal cortex(FC), corpus striatum(CS), hippocampus(H) cerebellum(CB) were dissected out from the whole brain. Activities of glutathione peroxidase(GSH-P(sub)x, superoxide dismutase(SOD) concentrations of malondialdehyde(MDA) were mesaured. Dietary fatty acids were not effective in antioxidative system for rat brain. However, when vitamin E was supplemented to the diet(ME), the activities of GSH-P(suh)x tended to increase in comparison to MO group. Therefore, the activites of GSH-P(suh)x of FC and H at the age of 3 weeks showed significant differences(p<0.05). The activities of Total-SOD tended to decrease in ME group compared to MO group. There were significant differences(p<0.05) in FC and CS at the age of 3 weeks. The activities of Mn-SOD tended to increase and Cu, Zn-SOD tended to decrease when vitamin E was supplemented. The activity levels of antioxidative enzymes at the age of 3 weeks and 9 weeks were similar. This suggested that the activity level of antioxidative enzymes reached to the adult level at the age of 3 weeks which is the end point of lactation period. The concentrations of MDA were not altered by experimental diets. When the activities of antioxidant enzymes were compared, the activities of antioxidant enzymes were the lowest in H and FC. In conclusion, the antioxidative system were not altered by dietary fatty acid at the age of 3 weeks and 9 weeks, but the supplementation of vitamin E altered the antioxidative systems. Therefore, these findings should be considered comprehensively in scope of the balance of various antioxidative systems and their interactions(Korean J Nutrition 34(1):14-22, 2001)

• The Korean Journal of Physiology and Pharmacology
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• 제12권4호
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• pp.131-135
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• 2008

The profile of membrane currents was investigated in differentiated neuronal cells derived from human neural stem cells (hNSCs) that were obtained from aborted fetal cortex. Whole-cell voltage clamp recording revealed at least 4 different currents: a tetrodotoxin (TTX)-sensitive $Na^+$ current, a hyperpolarization-activated inward current, and A-type and delayed rectifier-type $K^+$ outward currents. Both types of $K^+$ outward currents were blocked by either 5 mM tetraethylammonium (TEA) or 5 mM 4-aminopyridine (4-AP). The hyperpolarization-activated current resembled the classical $K^+$ inward current in that it exhibited a voltage-dependent block in the presence of external $Ba^{2+}$ (30 ${\mu}$M) or $Cs^+$ (3${\mu}$M). However, the reversal potentials did not match well with the predicted $K^+$ equilibrium potentials, suggesting that it was not a classical $K^+$ inward rectifier current. The other $Na^+$ inward current resembled the classical $Na^+$ current observed in pharmacological studies. The expression of these channels may contribute to generation and repolarization of action potential and might be regarded as functional markers for hNSCs-derived neurons.

• Applied Microscopy
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• 제38권3호
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• pp.265-273
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• 2008

본 연구는 국내에 거주하는 흑인종, 백인종, 황인종 여성의 모발을 채취하여 전자현미경으로 모발의 미세구조적 차이를 규명하였다. 흑인종 모발의 횡단면은 납작한 타원형의 형태를 하고 있었으며 황인종과 백인종 모발은 각각 원형과 타원형의 형태를 하고 있었다. 흑인종 모발은 두께가 $90{\sim}115{\mu}m$로 굵기가 일정하지 않았다. 황인종모발은 두께가 $100{\mu}m$이었으며 백인종 모발은 두께가 $80{\mu}m$로 측정되었다. 모발의 두께는 황인종 모발이 백인종 모발보다 크게 나타났다. 흑인종 모발은 황인종과 백인종 모발 보다 큐티클층이 많이 손상되어 있었다. 특히 큐티클세포의 내큐티클에는 많은 구멍들이 형성되어 있어서 쉽게 부서지는 특성이 나타났다. 백인종 모발의 피질에 있는 페오멜라닌은 내부에 동심원상의 나선구조를 하고 있었다.

• 대한본초학회지
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• 제28권2호
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• pp.93-101
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• 2013

Objects : Baicalein is a major bioactive flavonoid component of Scutellaria baicalensis Georgi that shows a wide range of biological activities, including neuroprotections and anti-inflammatory actions. Hence it is a potential therapeutic material for the treatment of neuroinflammation. In this study, we investigated the modulatory effect of baicalein on neuroinflammation. Method : Pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 mRNA), COX-2 mRNA expression and microglial activation in the brain tissue is induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Baicalein was treated orally with 10, 20, and 30 mg/kg 1 hour prior to the LPS (3 mg/kg, i.p.) injection. TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA expression in the brain tissue was measured by the quantitative real-time polymerase chain reaction(PCR) method. Iba1 expression in the brain was measured by western blotting method. Microglia was observed with immunohistochemistry. Results : Baicalein 30 mg/kg significantly attenuated the expression of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA in the brain tissue. Baicalein 20 mg/kg significantly attenuated the expression of IL-6 mRNA in the brain tissue. Baicalein 30 mg/kg significantly attenuated the expression of Iba1 protein expression in the brain tissue. Baicalein 30 mg/kg significantly decreased the number and cell size of microglia in the cerebral cortex and hypothalamic region and the area percentage of Iba1-expressed microglia in the hippocampus. Conclusion : These results demonstrated that baicalein attenuates LPS induced neuroinflammation in the mice via reduction of pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6), COX-2 mRNA expression and microglial activation.

• The Korean Journal of Physiology and Pharmacology
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• 제28권5호
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• pp.413-422
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• 2024

Group I metabotropic glutamate receptors (mGluRs) modulate postsynaptic neuronal excitability and epileptogenesis. We investigated roles of group I mGluRs on low extracellular Mg²⁺ concentration ([Mg²⁺]_o)-induced epileptiform activity and neuronal cell death in the CA1 regions of isolated rat hippocampal slices without the entorhinal cortex using extracellular recording and propidium iodide staining. Exposure to Mg²⁺-free artificial cerebrospinal fluid can induce interictal epileptiform activity in the CA1 regions of rat hippocampal slices. MPEP, a mGluR 5 antagonist, significantly inhibited the spike firing of the low [Mg²⁺]_o-induced epileptiform activity, whereas LY367385, a mGluR1 antagonist, did not. DHPG, a group 1 mGluR agonist, significantly increased the spike firing of the epileptiform activity. U73122, a PLC inhibitor, inhibited the spike firing. Thapsigargin, an ER Ca²⁺-ATPase antagonist, significantly inhibited the spike firing and amplitude of the epileptiform activity. Both the IP₃ receptor antagonist 2-APB and the ryanodine receptor antagonist dantrolene significantly inhibited the spike firing. The PKC inhibitors such as chelerythrine and GF109203X, significantly increased the spike firing. Flufenamic acid, a relatively specific TRPC 1, 4, 5 channel antagonist, significantly inhibited the spike firing, whereas SKF96365, a relatively non-specific TRPC channel antagonist, did not. MPEP significantly decreased low [Mg²⁺]_o DMEM-induced neuronal cell death in the CA1 regions, but LY367385 did not. We suggest that mGluR 5 is involved in low [Mg²⁺]_o-induced interictal epileptiform activity in the CA1 regions of rat hippocampal slices through PLC, release of Ca²⁺ from intracellular stores and PKC and TRPC channels, which could be involved in neuronal cell death.