• 한국연초학회지
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• 제13권1호
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• pp.19-26
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• 1991

Ames test using special strains which are histidine requiring mutant of Salmonella typhimufium , is widely utilized as short-term bioassay to evaluate the genotoxicity of chemicals. This method requires the liver microsome(5-9 fraction) to provide mammalian metabolism of the compounds, Therefore, the mutagenic potency of the chemicals is affected by not only the intrinsic properties of them but also the efficiency of the in vitro microsomal activation system. For this reason, the complex mixtures such as environmental pollutants from occupational sources, natural products or cigarette smoke condensates(CSC) , might be often appeared the false results. Induction of sister chromatid exchange(SCE) in cultured cells is known as another sensitive and powerful tool for the measurement of genotoxicity and the method has also an advantage which is able to apply to the in vitro and in vivo systems. In the present study, the inducibilities of revertant colonies in tester strain TA98 and SCE in human Iymphocytes by positive controls and total particulated materials(TPM) obtained from various brand(domastic and imported) cigarettes were compared in order to investigate whether the results in Ames test are in agreement with those in SCE analysis. The mutagenic activities of well known mutagens such as B(a)P showed excellent dose-response in the both methods although the induction mechanism was different each other, but cyclophosphamide resulted such effect only in SCE analysis. Most TPM tested showed a similar pattern in the mutagenic activities in those methods. However, only two(one imported brand and one domestic sample cigarettes) among the TMP obtained from various cigarettes appeared the higher induction in SCE than Ames test.

• 생약학회지
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• 제30권4호
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• pp.384-396
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• 1999

Acyl-CoA: Cholesterol Acyltransferase (ACAT) is a key enzyme responsible for cholesteryl ester formation in atherogenesis and in cholesterol absorption from the intestines. In addition under pathological conditions, formation and accumulation of cholesteryl ester as lipid droplets by ACAT within macrophages constitute a characteristic feature of early lesions of atherosclerotic plaques. ACAT inhibitors are expected to be effective for treatment of atherosclerosis and hypercholesterolemia. ACAT inhibitors of natural origin have been rarely reported. In our screening program for ACAT inhibitors, 303 plants were extracted with methanol or ethanol, and screened for the inhibitory activity against ACAT from the rat liver microsome. Extracts of 13 plants including Quercus aliena, Diospyros kaki, Platycarya strobilacea and Hibiscus syriacus inhibited more than 90% of ACAT activity and 43 samples in alcohol extracts such as Magnolia obovata and Panax ginseng also inhibited more than 70% of ACAT activity at a concentration of $100\;{\mu}g/ml$.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.340-340
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• 1994

Since total hepatic ischemia(IS) occurs with transplantation, there has been interest in evaluating hepatic function after ischemia and subsequent reflow of blood. Four groups of animals were studied: group 1 (sham), group 2 (30mins IS), group 3 (60mins IS), and g.cup 4 (90mins IS). Serum transaminase(STA), wet weight-to-dry weight ratio(W/D), lipid peroxides(LPO), glucose-6-phosphatase(G-6-Pase) activity, Na$\^$+//K$\^$+/-ATPase(ATPase) activity were measured at 1, 5 and 24hrs after hepatic ischemia. Significant changes occurred between 1 and 5hrs of reperfusion. STA was 3579${\pm}$401, 4593${\pm}$675 and 6348${\pm}$808 U/L in group 2, 3 and 4 respectively. These changes were ischemic time-dependent manner. W/D in group 3 and 4 were significantly increased than that in sham group at all time points measured. In sham group, the level of LPO in the liver microsome remained constant at approximately 0. 5nmole MDA formed/mg protein througllout the experiment, In all ischemic groups on the other hand, the level of LPO started to increase at ischemia and markedly increased at all reperfusion period. Similar to STA, these changes were also dependent on duration of ischemia. Although G-6-Pase activity remained unchanged in both group 2 and group 3 until 5hrs of reperfusion, marked decrease in G-6-Pase activity was observed at grcup 4. ATPase activity was significantly decreased at 1, 5 and 24 hrs of reperfusion in group 3, whereas it was not changed in group 2. Furthermore, ATPase activity in group 4 started to decrease at ischemia and markedly decreased for entire reperfusion period. These data suggest that severity of hepatocellular injury is associated with period of ischemia as well as period of reperfusion.

• Nutrition Research and Practice
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• 제4권1호
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• pp.11-15
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• 2010

The purpose of the present study was to investigate the effect of ethanol extracts from red pepper seeds on the antioxidative defense system and oxidative stress in rats fed a high fat high cholesterol diet. Rats were divided into four experimental groups which were composed of high fat high cholesterol diet group (HF), high fat high cholesterol diet with 0.1% ethanol extracts from red pepper seeds supplemented group (HEA), high fat high cholesterol diet with 0.2% ethanol extracts from red pepper seeds supplemented group (HEB) and high fat high cholesterol diet with 0.5% ethanol extracts from red pepper seeds supplemented group (HEC). Supplementation of ethanol extracts from red pepper seeds groups (HEA, HEB and HEC) resulted in significantly increased activities of hepatic glutathione peroxidase and catalase. Hepatic superoxide radical contents in microsome and mitochondria were significantly reduced in the groups supplemented with red pepper seeds ethanol extracts. Hepatic hydrogen peroxide content in the mitochondria was reduced in ethanol extracts from red pepper seeds supplemented groups. TBARS values in the liver were reduced in red pepper seeds ethanol extracts supplemented groups. Especially, HEB and HEC groups were significantly decreased compared to the HF group. Hepatic carbonyl values were significantly reduced in mitochondria in these supplemented groups. These results suggest that red pepper seeds ethanol extracts may reduce oxidative damage, by activation of antioxidative defense system in rats fed high fat high cholesterol diets.

• 한국약용작물학회지
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• 제24권1호
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• pp.7-13
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• 2016

Background : Ginger has been extensively used in foods and traditional medicines in Asian countries. Despite its frequent consumption in daily life, the mechanism of potential interactions between ginger components-drug has not been examined. To elucidate the mechanism of governing the effects of 6-shogaol, a primary constituent of dried ginger, on human cytochrome P450 (CYP) isoenzymes an incubation studies were carried out using pooled human liver microsome (HLM). Methods and Results : CYP isoenzyme specific substrate was incubated with multiple concentrations of inhibitor, HLM and cofactors. 6-shogaol showed a potent inhibitory effect on CYP2C9, CYP1A2 and CYP2C19 with half maximal inhibitory concentration ($IC_{50}$) values of 29.20, 20.68 and $18.78{\mu}M$ respectively. To estimate the value of the inhibition constant ($K_i$) and the mode of inhibition, an incubation study with varying concentrations of each CYP isoenzyme-specific probe was performed. 6-shogaol inhibited CYP2C9 and CYP2C19 noncompetitively ($K_i=29.02$ and $19.26{\mu}M$ respectively), in contrast, the inhibition of CYP1A2 was best explained by competitive inhibition ($K_i=6.33{\mu}M$). Conclusions : These findings suggest that 6-shogaol may possess inhibitory effects on metabolic activities mediated by CYP1A2, CYP2C9 and CYP2C19 in humans.

• 대한화장품학회지
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• 제20권1호
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• pp.1-13
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• 1994

솔잎으로부터 프리 라디칼 소거 작용이 있는 물질을 분리하고, 여러 기기 분석 결과에 근거하여 4-hydroxy-5-methyl-3[2H]-furanone (HMF) 으로 동정하였다. 이 물질이 1, 1-diphenyl-2-picrylhydrazyl 프리 라디칼에 대한 소거 작용이 공지의 항산화 물질인 a-tocopherol, ascorbic acid와 유사하였다. HMF는 흰쥐 간 microsome분획에서 Fe(II)/ascorbate에 의해 유도된 지질 과산화를 억제하였으며, 배양 fibroblast 세포에서 자외선에 대한 보호효과를 나타내었다. 이 물질은 또한 tyrosine의 효소적 산화와 Dopa의 자동 산화를 억제하였을 뿐만 아니라 배양 murine melanoma 세포에서도 강력한 멜라닌 생성 억제 작용을 보였다. 피부 세포에서의 멜라닌 생성이 산화적 스트레스에 의해 유발되고 또 효소, 비효소적인 산화 반응을 통해 진행된다고 볼 때, HMF는 이러한 각 단계에서 항산화제로 작용하여 궁극적으로 세포에서의 멜라닌 생성을 막는 것으로 추론되었다.

• KSBB Journal
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• 제15권2호
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• pp.150-155
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• 2000

본 연구는 Streptomyces sp. BH-405의 배양액으로부터 유기용매로 추출하여 지질과 산화에 대한 항산화 효과를 실험하였다. Streptomyces sp. BH-405의 배양액을 ethylether로 추출한 후 silica gel column(100$\times$10 cm) chromatography로 분획한 획분을 POV로 측정한 결과 fraction 3에서 향산화 활성이 가장 높았다. 항산화 활성이 높은 fraction 3 획분을 다시 preparative TLC와 column chromatography로 더욱 정제하여 band 2를 얻었다. Band 2의 항산화 효과를 알아보기 위해 기존의 항산화제와 비교한 결과 이-$\alpha$-tocopherol, BHA보다 산화억제 효과가 높았으며 DPPH에 의한 수소 공여능은 실험결과가 우수하였다. 한편 band 2는 쥐 간의 microsome에 있어서 유리기의 소거기능이 있었고 NADPH 및 Fenton 시액에 위한 효소적 과산화 지질의 생성을 억제하였다. 그리고 mitochondria와 리놀산의 과산화 유도계에서도 지질의 과산화 과정에 생성하는 유리기의 형성을 차단하였다. 결론적으로 Streptomyces sp. BH-405의 배양액에서 얻은 획분인 band 2는 산화를 억제하는 활성이 있었다.

• Journal of Nutrition and Health
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• 제29권2호
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• pp.232-241
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• 1996

This study was designed to compare the effect of different dietary fats on plasma lipids, the degree of lipid peroxidation and the activity of antioxidant enzymes in RBC and liver rats treated with or wighout 1, 2-dimethylhydrazing (DMH). Male Sprague Dawley rats, at 7 weeks-old, were divided into control and DMH-treated grous, and each group was again subdivided into four were perilla oil (PO), blend fat (BF) containing ten different kinds of dietary oil, beef tallow (BT), corn oil (CO). At the same time, each rat was injected intramusculary with saline(for control) or DMH twice a week for 6 weeks to give total dose of 180 mg/kg body weight. Compared with BT feeding, BF reduced plasma total choesterol level and PO and Co reduced plasma TG levels (p<0.05). DMH injection decreased plasma cholesterol in all dietary groups. However, PO decreased tocopherol levels and increased TBARS levels in RBC compared to BT. The degree of hemolysis in PO group was higher than that of BT group (p<0.05 only in control group. Fatty acid composition of hepatic microsome was reflected by dietary fatty acid profile. The peroxidizability index and TBARS level in hepatic micorsome were significantly increased but tocopherol level was lowered in PO group compared to BT group. Activites of superoxide dismutase and glutathione peroxidase in RBC and hepatic cytosol were not influenced y dietary fats and DMH treatment(p<0.05). Overall, perilla oil rich in $\omega$3 $\alpha$-linolenic acid could be a very important dietary source in reducing plasma lipids and blend fat was also good dietary oil mixture in reducing plasma cholesterol. However, the degree of lipid peroxidation was greater in tissue by perilla oil feeding and it is very difficult to use only perilla oil as oil source for meal preparation, so that it could be suggested to use more perilla oil and fish to give an equal effect of blend fat in order to reduce the risk factors against cardiovascular disease.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.344-353
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• 2020

This study aims to develop new potential therapeutic moracin M prodrugs acting on lung inflammatory disorders. Potential moracin M prodrugs (KW01-KW07) were chemically synthesized to obtain potent orally active derivatives, and their pharmacological activities against lung inflammation were, for the first time, examined in vivo using lipopolysaccharide (LPS)-induced acute lung injury model. In addition, the metabolism of KW02 was also investigated using microsomal stability test and pharmacokinetic study in rats. When orally administered, some of these compounds (30 mg/kg) showed higher inhibitory action against LPS-induced lung inflammation in mice compared to moracin M. Of them, 2-(3,5-bis((dimethylcarbamoyl)oxy)phenyl)benzofuran-6-yl acetate (KW02) showed potent and dose-dependent inhibitory effect on the same animal model of lung inflammation at 1, 3, and 10 mg/kg. This compound at 10 mg/kg also significantly reduced IL-1β concentration in the bronchoalveolar lavage fluid of the inflamed-lungs. KW02 was rapidly metabolized to 5-(6-hydroxybenzofuran-2-yl)-1,3-phenylene bis(dimethylcarbamate) (KW06) and moracin M when it was incubated with rat serum and liver microsome as expected. When KW02 was administered to rats via intravenous or oral route, KW06 was detected in the serum as a metabolite. Thus, it is concluded that KW02 has potent inhibitory action against LPS-induced lung inflammation. It could behave as a potential prodrug of moracin M to effectively treat lung inflammatory disorders.

• 생명과학회지
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• 제21권7호
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• pp.1016-1024
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• 2011

영지버섯, 여주, 쓴메밀 및 이들 혼합 시료의 70% 메탄올 추출물을 이용하여 생리활성물질(폴리페놀 화합물 및 플라보노이드) 농도와 항산화(DPPH radical 소거 활성, 생체막 지질과산화, Fe/Cu 환원력), ${\alpha}$-glucosidase 저해, tyrosinase 저해 및 항혈전 활성에 대하여 검토하였다. 추출 수율과 폴리페놀 화합물 및 플라보노이드의 함량은 혼합 추출물에서 가장 높았다. 또한 혼합 추출물에서 ${\alpha}$-glucosidase 저해, tyrosinase 저해, 항산화, 환원력 및 항혈전 활성은 혼합 추출물에서 가장 높았으며, 이러한 효과는 처리 농도 의존적 이였다. 이상의 실험 결과에서 영지버섯, 여주, 쓴메밀의 혼합 메탄올 추출물은 폴리페놀 화합물과 플라보노이드를 많이 함유함으로서 높은 ${\alpha}$-glucosidase 저해 및 항산화 활성과 관련성이 높아 보여 항당뇨 건강 기능성식품의 소재 개발에 활용될 가능성이 높아 보인다.