• 통합자연과학논문집
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• 제8권4호
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• pp.258-266
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• 2015

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, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMFA) 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 CoMFA 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 CoMFA models were generated using different alignments and the best model yielded a cross-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 CoMFA models was found to be $r^2_{pred}$0.653. The CoMFA study revealed that the $R_3$ position of the structure is important in influencing the biological activity of the inhibitors. Electro positive groups and bulkier substituents in this position enhance the biological activity.

• 동아시아식생활학회지
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• 제19권2호
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• pp.195-201
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• 2009

The antioxidative activities of two varieties of egg plant (Chunyang No 2: Dangaji, Jinju Janggaji: Janggaji) extracts were investigated. The total polyphenol contents of Dangaji peel hot water extract and the Janggaji flesh and fruit hot water extracts were higher than those of the other samples. However, the DPPH radical scavenging activities(electron donating activity) of Dangaji flesh-ethanol, peel-cold water, and fruit- ethanol extracts, as well as the Janggaji peel cold water extract, were higher than those of the other samples. Furthermore, the in vitro inhibitory effects of the Dangaji peel cold water and hot water extracts on rat hepatic xanthine oxidase were highest among the samples, and were exhibited in a dose dependant manners. Although there were marked changes in the xanthine oxidase Km values for xanthine as a substrate, the Vmax value changes by the addition of the Dangaji water extracts were minor compared with the control. This result suggests that Dangaji water extracts may regulate the activity of xanthine oxidase-via the inhibition of binding affinity between the enzyme and substrate. The present study provides experimental evidence that constituents of egg plant extracts may ameliorate reactive oxygen species(ROS)-induced oxidative stress via hepatic hepatic xanthine oxidase activity, but further studies to identify the active antioxidants and compounds and inhibitors of xanthine oxidase are required.

• 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.

• 한국식품영양과학회지
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• 제36권4호
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• pp.389-394
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• 2007

한방생약자원으로 사용되는 가죽나무(A. altissima)의 생리학적 활성을 조사하고자 뿌리와 줄기, 잎을 에탄올을 용매로 추출하여 농도에 따라 전자공여능, SOD유사활성, 아질산염 소거능을 측정하였으며, xanthine oxidase와 tyrosinase 저해 활성을 측정하였다. 전자공여능은 $1,000{\mu}g/mL$의 농도에서 뿌리와 줄기 추출물이 64.04%와 63.27%이었으며, 잎 추출물은 17.47%를 나타내었다. SOD 유사활성능은 $7.66%{\sim}50.00%$로 잎 추출물이 뿌리와 줄기에 비해 약 5배 이상 높았고, 아질산염 소거능에 있어서도 가죽나무 잎 추출물이 $1,000{\mu}g/mL$의 농도에서 pH 1.2와 3.0에서 98%이상의 높은 소거효과를 나타내었으며 $500{\mu}g/mL$의 농도에서도 90% 이상의 소거효과를 나타내었다. Xanthine oxidase저해 활성은 $1,000{\mu}g/mL$ 농도에서 뿌리와 줄기, 잎 추출물 모두에서 90% 이상의 저해율을 보였고, tyrosinase저해는 $2,000{\mu}g/mL$의 농도에서 뿌리 추출물이 62.01%로 가장 높은 저해효과를 나타내었으며, $100{\mu}g/mL$의 농도에서도 57.70%의 저해 활성을 나타내었다. 그러므로 가죽나무는 한방생약자원으로 이용되는 뿌리(저근백피) 이외에도 잎은 높은 SOD 유사활성능과 아질산염 소거능을 나타내며 줄기에서도 뿌리보다 높은 전자공여능과 아질산염 소거능 및 유사한 xanthine oxidase 저해 활성을 나타내므로 유용한 한방생약자원인 것으로 판단된다.

• 한국식품영양학회지
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• 제17권4호
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• pp.347-355
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• 2004

초석잠 메탄올 추출물이 뇌신경전달물질과 관련이 있는 acetylcholine esterase, monoamine oxidase 및 xanthine oxidase의 활성억제효과에 대하여 실험하였다. 실험관내에서 초석잠 추출물을 각각 100 및 200mg/kg씩 첨가한 다음 실험한 결과 첨가농도가 증가할수록 과산화지질의 생성을 억제하여 용량 의존형으로 나타났다. 쥐를 대상으로 20일간 투여한 동물실험에서는 초석잠 추출물 100 mg/kg을 식이에 혼합하여 투여한 결과 지질 과산화의 생성을 억제하였다. Acetylcholine esterase의 활성의 경우 초석잠 추출물을 100 mg/kg 투여한 결과 대조군에 비하여 효소활성이 23.11%로 억제되었고, monoamine oxidase 및 xanthine oxidase 활성이 각각 21.93% 및 63.58%로 억제되었다. 그리고 초석잠 추출물을 100 mg/kg을 투여한 경우 xanthine dehydrogenase로부터 xanthine oxidase로의 형전환비율은 28%로 현저하게 억제되었다. 또한, Xanthine dehydrogenase로부터 oxidase로의 형전환비율을 실험한 결과 정상상태에 비하여 억제됨을 알 수 있었다.

• 한국식품영양과학회지
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• 제39권11호
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• pp.1573-1579
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• 2010

본 연구에서는 솔순의 기능성을 규명하기 위해 열수 추출물을 대상으로 여러 생리활성과 아질산염 소거작용에 대하여 분석하였다. 우선, 솔순의 항산화 활성을 측정하기 위하여 DPPH, SOD 유사활성, XO 저해활성을 측정하였다. 그결과 DPPH법을 통해 측정한 솔순의 항산화력은 2 mg/mL에서 71.4%의 radical 소거능을 나타내었으며, SOD 유사활성은 2 mg/mL 농도에서 85.4%로 비교적 높은 활성을 나타내었다. Xanthine oxidase 저해활성 측정 실험에서는 2 mg/mL에서 70.9%의 높은 저해활성을 나타내었다. 솔순 열수추출물의 아질산염 소거능 측정 실험에서는 pH 1.2와 3.0에서 53~59%, pH 6.0에서 40%의 소거능을 나타내었다. 항고 혈압 측정실험에서는 시판되는 항고혈압제 captopril과 비교분석 하였는데, 0.1 mg/mL에서 93.0%였고 같은 농도의 솔순 열수 추출물은 14.6%의 낮은 저해율을 나타냈다. 하지만, 1 mg/mL에서 44.7%의 저해율을 나타내어 솔순 열수 추출물의 비교적 양호한 저해활성을 보였다. 혈당강하능의 지표로 $\alpha$-glucosidase 활성 억제능을 분석한 결과 솔순 열수 추출물 3 mg/mL의 농도에서 43.3%의 저해활성을 나타냈으며, 주름 예방 효과의 지표로 elastase 활성 억제능을 측정한 결과 10 mg/mL의 농도에서 59.6%의 저해능을 보였다. 이상의 결과들은 솔순 열수 추출물의 우수한 생리활성을 증명하고 있는 것으로 천연의 건강 및 미용 소재로써 그 활용도가 높을 것으로 판단된다.

• Archives of Pharmacal Research
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• 제17권2호
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• pp.109-114
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• 1994

The role of sex homones in hepatic lipid peroxidation, and in hepatic adehyde odidase and xanthine oxidase activites were investigated using rat liver homogenates. It was observed that male rt had a significantly greater content of malondialdehyde in liver than female. Among the sex hormones tested, estradiol, one of female hormones, markedly inhibited the formation of lipid peroxides in liver tissues in vitro. Especially, the inhibitory effect of estradiol appeared more remarkably in Fe-induced lipid peroxidation. The hepatic xanthine oxidase activity was decreased about 15% by $10\;^6\;M$ estradiol, wherease, the adehyde oxidase activity was almost completely disappeared at the same concentration of estradiol. It implies that sex differences in lipid peroxidation is attributed to the suppression of radical generating system by estradiol.

• Mycobiology
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• 제42권3호
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• pp.296-300
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• 2014

We selected Pleurotus ostreatus from among several edible mushrooms because it has high anti-gout xanthine oxidase (XOD) inhibitory activity. The maximal amount of XOD inhibitor was extracted when the Pleurotus ostreatus fruiting body was treated with distilled water at $40^{\circ}C$ for 48 hr. The XOD inhibitor thus obtained was purified by Sephadex G-50 gel permeation chromatography, ultrafiltration, $C_{18}$ solid phase extraction chromatography and reverse-phase high-performance liquid chromatography with 3% of solid yield, and its XOD inhibitory activity was 0.9 mg/mL of $IC_{50}$. The purified XOD inhibitor was a tripeptide with the amino acid sequence phenylalanine-cysteine-histidine and a molecular weight of 441.3 Da. The XOD inhibitor-containing ultrafiltrates from Pleurotus ostreatus demonstrated dose-dependent anti-gout effects in a Sprague-Dawley rat model of potassium oxonate-induced gout, as shown by decreased serum urated levels at doses of 500 and 1,000 mg/kg, although the effect was not as great as that achieved with the commercial anti-gout agent, allopurinol when administered at a dose of 50 mg/kg.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 춘계학술발표회
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• pp.95-95
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• 2018

Uric acid is the end product of purine metabolism in human body, originating from hypoxanthine after enzyme catalysis by Xanthine oxidase (XOD). Hyperuricemia results as a result of either over-generation of uric acid or a reduction in its excretion. In silico modelling methods such as Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) prediction, Autodock 4.2.6 program were used to study the potential inhibitory compounds of XOD. Also we investigated the inhibition of XOD activity by using the extracts of Dendropanax morbifera and Rubus coreanus Miq spectrophotometrically. According to ADMET data, several compounds from D. morbifera and R. coreanus plants, were found to be more potent in inhibiting the XOD activity than allopurinol. XOD inhibitory activity is evaluated by quantifying the formation of uric acid by measuring the absorbance at 290 m ($A_{290}$).D. morbifera extract inhibited XOD activity at $250{\mu}g/ml$, however the extracts from R. coreanus has inhibited XOD activity at $25{\mu}g/ml$. The major compound of R. coreanus, ellagic acid significantly increased the inhibition rate from $9{\mu}g/ml$ and showed a 71% suppression rate at $15{\mu}g/ml$. Finally, these results suggested a potential inhibitory activities of the extracts from D. morbifera and R. coreanus Miq, but further research is needed to validate to ensure their safe usage as drug.

• Preventive Nutrition and Food Science
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• 제16권1호
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• pp.8-11
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• 2011

In this study, we assessed the free radical scavenging and xanthine oxidase inhibitory activities of extracts isolated from the dried roots and stems (including leaves) of Angelica dahurica. The irritation response from these extracts was also assessed to determine potential cosmetic use. Both sources of A. dahurica extracts exhibited radical scavenging properties to different extents. The free radical scavenging potency ($EC_{50}$) of the stems (including leaves) of A. dahurica was 243.33 ${\mu}g/mL$, which is significantly lower (p<0.01) than that observed of the roots (1,161.79 ${\mu}g/mL$). The inhibition values ($EC_{50}$) of xanthine oxidase were as follows: 435.19 ${\mu}g/mL$ (roots) and 434.66 ${\mu}g/mL$ (stems). We noted no significant differences between the two plant parts with regard to ability to inhibit xanthine oxidase activity. After the application of A. dahurica extracts to rabbits for skin and eye irritation tests, no negative effects were observed; therefore, the extracts are considered to be non-irritating to the skin and eye.