• 한국식품과학회지
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• 제24권6호
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• pp.558-562
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• 1992

Xanthine oxidase는 퓨린 대사에 관여하여 xanthine 혹은 hypoxanthine을 산화하여 요산을 생성하게 하는 효소이다. 이상 퓨린 대사로 인해 형성된 요산은 관절에 축적되어 통풍을 동반하는 통증을 유발한다. 본 연구는 천연물로부터 통풍치료제의 개발을 목적으로 우롱차로 부터 6종의 flavan-3-ol 화합물을 분리하였고 기기분석에 의해 화학구조를 밝혔다. 각 화합물은 (-)-epicatechin, (-)-epicatechin-3-O-gallate, procyanidan B-1, B-3, procyanidin B-3-3'-O-rhamnose procyanidin B-1-3-O-gallate 였다. Xanthine oxidase 저해 영향을 관찰한 결과 gallte가 결함된 flavan-3-ol 화합물이 저해활성이 강하였고 procyanidin B-1-3-O-gallate는 $50\;{\mu}M$에 완전한 저해효과를 나타내었고 xanthine oxidase에 경쟁적으로 저해한다는 것이 밝혀졌다.

• Journal of Nutrition and Health
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• 제33권7호
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• pp.739-744
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• 2000

The purpose of this study was to elucidate protective effect of Fructus Schsandrae(FS) water extract against xanthine oxidase/hypoxanthine(XO/HX)-induced cardiotoxicity in myocardial cells this experiment was performed. Cardiotoxicity of XO/HX was examined by MTT(MTT [3-(4,5-dimethylthiazol-2-yl)-2.5,-diphenyl tetrazolium bromide) assay. XO/HX induced the decrease of cell viability. Also XO/HX induced the increase of LDH activity and the decrease of beating rate on cultured myocardial cells in a dose-dependent manner. To investigate cardioprotective effect of FS water extract cultures were preincubated with FS water extract for 3 hours. Cultures were then exposed to XO/HX for 72 hours. FS water extract have an efficacy in decreaasing LDH activity and increasing heart beating rate on cultured myocardial cells damaged by XO/HX. From the results it is suggested that XO/HX may show toxic effect in cultured myocardial cells derived from neonatal mouse and FS water extract is effective in the prevention of XO/HX-induced cardiotoxicity.

• 대한한의학회지
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• 제21권1호
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• pp.29-39
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• 2000

In order to elucidate the toxic mechanism of oxygen radicals in cultured mouse spinal sensory neurons, cytotoxic effect of oxygen radicals was evaluated by M1T assay and NR assay. In addition, protective effect of Sopunghwalhyultang(SPHHT) water extract on oxidant-induced neurotoxicity was investigated on these cultures. Spinal sensory neurons derived from mice were cultured in mediums containing various concentrations of Xanthine Oxidase / Hypoxanthine(XO/HX). Cell viability was measured by MTT assay and NR assay. XO/HX-mediated oxygen radicals remarkably decreased cell viability of cultured spinal sensory neurons in a dose-and time-dependent manner. And also, SPHHT blocked XO/HX-induced neurotoxicity in these cultures. These results suggest that oxygen radicals are toxic and SPHHT are effective in blocking against the oxidant-induced neurotoxicity in cultures of spinal sensory neurons of mice.

• 대한한의학회지
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• 제20권4호
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• pp.3-10
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• 2000

In order to elucidate the toxic mechanism of neurotoxical damage and neuroprotective effect of Jangwon-hwan(Zhuangyuan-wan) water extract, this experiment was performed. Neurotoxic effects of xanthine oxidase/hypoxanthine(XO/HX) were examined by MTT and NR assay, neuroprotective effects of Jangwon-hwan(Zhuangyuan-wan) water extract were examined by neurofilament enzymeimmuno assay(EIA). XO/HX induced an increase in cell viability, and a decrease in the amount of neurofilament on cultured mouse cerebral cortical neurons in dose-dependent manner. In neuroprotective effect of herb medicine, Jangwon-hwan(Zhuangyuan-wan) water extract increased the amount of neurofilament on cultured mouse cerebral cortical neurons damaged by XO/HX. From the results, it is suggested that XO/HX showed toxic effect in cultured mouse cerebral cortical Neurons and Jangwon-hwan(Zhuangyuan-wan) water extract is very effective in the prevention of neurotoxicity induced by XO/HX.

• 통합자연과학논문집
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• 제10권4호
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• pp.202-208
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• 2017

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organs including the liver, gut, lungs, kidney, heart, brain and plasma. It is involved in gout pathogenesis. Hence, in the present study, Hologram based Quantitative Structure Activity Relationship Study was performed on a series of Xanthine Oxidase antagonist named 2-(indol-5-yl) thiazole derivatives. The best HQSAR model was obtained using Atoms, Bonds, Connection, Hydrogen, Chirality and Donor Acceptor as fragment distinction parameter using hologram length 71 and 4 components with fragment size of minimum 2 and maximum 5. Significant cross-validated correlation coefficient ($q^2$= 0.563) and non cross-validated correlation coefficients ($r^2$= 0.967) were obtained. The model was then used to evaluate the six external test compounds and its $r^2{_{pred}}$ was found to be 0.798. Contribution map show that presence of propyl ring in indole thiazole makes big contributions for improving the biological activities of the compounds. We hope that our HQSAR model and analysis will be helpful for future design of xanthine oxidase antagonists.

• 통합자연과학논문집
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• 제10권4호
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• pp.192-196
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• 2017

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organs including the liver, gut, lungs, kidney, heart, brain and plasma. It is involved in gout pathogenesis. Hence, in the present study, topomer based Comparative Molecular Field Analysis (topomer CoMFA) was performed on a series of Xanthine oxidase antagonist named 2-(indol-5-yl) thiazole derivatives. The best topomer CoMFA model was obtained with significant cross-validated correlation coefficient ($q^2$ = 0.572) and non cross-validated correlation coefficients ($r^2$ = 0.937). The model was evaluated with six external test compounds and its $r^2{_{pred}}$ was found to be 0.553. The steric and electrostatic contribution map show that presence of bulky and electropositive group in indole thiazole ring is necessary for improving the biological activities of the compounds. The generated topomer CoMFA model could be helpful for future design of novel and structurally related xanthine oxidase antagonists.

• 대한한의학방제학회지
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• 제8권1호
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• pp.319-328
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• 2000

To evaluate the effect of Baepungtang(BPT) water extract on cultured mouse spinal sensory neuron which was inhibited by xanthine oxidase(XO) and hypoxanthine(HX)-induced oxigen radicals, MTT assay, NR assay, Neurofilament enzymeimmuno assay and LDH activity assay were carried out after the cultured mouse spinal sensory neuron were preincubated with various concentrations of BPT water extract for 3 hours prior to exposure of XO/HX. The results obtained were as follows: 1. XO/HX, a oxigen radical, decreased the survival rate of the cultured mouse spinal sensory neuron cell on NR assay and MTT assay. 2. $MTT_{50}$ value and $NR_{50}$ value of XO/HX were 30 mU/ml XO/O.2 mM HX. 3. BPT water extract have efficacy of increasing neurofilament. 4. BPT water extract have efficacy of increasing LDH activity. From above the results, It is concluded that BPT has marked efficacy as a treatment for the damages caused in the XO/HX-mediated oxidative process.

• 한국식품영양과학회지
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• 제25권6호
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• pp.1069-1073
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• 1996

해조류의 기능특성 해석의 일환으로 해조류 중 갈조류인 미역 (Undaria pinnattnda), 감태 (Ecklonia stolonifera), 곰피(Ecklonia cava), 다시마(Laminaria japonica) 및 모자반(Sargussum fulvellum)과 녹조류인 청각(Codium fragile), 파래(Enteromorpha compressa) 및 홍조류인 김(Porphyra tenera)등을 시료로 하여, 생체내 퓨린대사에서 xanthine 및 hypoxanthine으로 부터 요산을 형성, 혈액 중 이상 고요산 증상에 의하여 신장질환 및 통풍을 유발하는 효소인 xanthine oxidase 저해작용에 대하여 살펴 본 결과, 갈조류의 다시마과 Ecklonia 속인 감태와 곰피가 가장 높은 저해율을 나타내었으며, 용매 추출물에 있어서는 diethyl ether>ethyl acetate>chloroform>수용성 획분의 순으로 나타났다. 또한 xanthine oxidase 저해작용이 가장 높은 감태 diethyl ether 추출물을 silica gel column chromatography, thin layer chromatography 및 HPLC를 통하여 xanthine of idase 저해 인자를 분리한 결과, xanthine oxidase 저해작용이 가장 강한 활성성분은 420, 456, 467nm에서 흡수파장을 가지는 물질로서, 이는 siphonaxanthine인 것으로 추정되었다.

• 동의생리병리학회지
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• 제16권4호
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• pp.720-723
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• 2002

To clarify the vasculotoxicity of reactive oxygen intermediate(ROI) in cultured vascular endotherial cells(VEC), of mouse, cytototoxicity was measured by MTS assay after VEC was incubated to 10～80mU/ml xanthine oxidase(XO) and hypoxanthine(HX) for 2 hours. and also, the protective effect of Radix Polygoni Multiflori(RPM) was determined by MTT assay in these cultrures. Cell viability was positively decreased dose-, and time-dependently, after the treatment with 40mU/ml XO/0.1 mM HX to cultured VEC for 2 hours. In the vasculoprotective effect of RPM on the toxicity induced by XO/HX, RPM prevented the XO/HX-induced cytotoxicity in these cultures. From above the results, it suggests that XO/HX is toxic in cultured VEC and herb extract, RPM has protective effect against the vasculotoxicity induced by XO/HX.

• 통합자연과학논문집
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• 제9권3호
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• pp.190-198
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• 2016

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organsincluding the liver, gut, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMSIA) on a series of 2-(indol-5-yl) thiazole derivatives as xanthine oxidase (XO) inhibitors to identify the structural variations with their inhibitory activities. Ligand based CoMSIA models were generated based on atom-by-atom matching alignment. In atom-by-atom matching, the bioactive conformation of highly active molecule 11 was generated using systematic search. Compounds were aligned using the bioactive conformation and it is used for model generation. Different CoMSIA models were generated using different alignments and the best model yielded across-validated $q^2$ of 0.698 with five components and non-cross-validated correlation coefficient ($r^2$) of 0.992 with Fisher value as 236.431, and an estimated standard error of 0.068. The predictive ability of the best CoMSIA models was found to be $r{^2}_{pred}$ 0.653. The study revealed the important structural features required for the biological activity of the inhibitors and could provide useful for the designing of novel and potent drugs for the inhibition of Xanthine oxidase.