• Journal of Integrative Natural Science
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• v.8 no.4
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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.

• Journal of the East Asian Society of Dietary Life
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• v.19 no.2
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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.

• Journal of Integrative Natural Science
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• v.9 no.3
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.4
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• pp.389-394
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• 2007

The study was carried out to optimize the electron donating ability (EDA), superoxide dismutase (SOD)-like activity, nitrite scavenging ability, and the inhibitory activities of xanthine oxidase and tyrosinase of Ailanthus altissima ethanol extracts from roots, stems and leaves. The EDA of the roots and stem extracts were 64.04% and 63.27% at $1,000{\mu}g/mL$, respectively. The SOD-like activity of the leaves extract was the highest (50.00%) at $1,000{\mu}g/mL$. The nitrite scavenging ability of the leaves extracts was over 98% at pH 1.2 and 3.0. The xanthine oxidase inhibitory rates of the extracts were $93.62%{\sim}95.40%$ and the tyrosinase inhibitory rate of the roots was the highest (62.01%) at the concentration of $1,000{\mu}g/mL$. These results indicated that the roots extract showed the highest EDA and tyrosinase inhibition, while the leaves extract had tile highest SOD-like activity and nitrate scavenging ability.

• The Korean Journal of Food And Nutrition
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• v.17 no.4
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• pp.347-355
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• 2004

This study was undertaken in order to evaluate effects of methanol extracts of Stachys sieboldii MIQ and its related enzyme activities in brain tissues of rats. Sprague-Dawley(SD) male rats were fed within a control group, which is a basic diet group. The experimental diet group was given 100 and 200 mg/kg to supervise 100 and 200 mg/kg body weight per day for 20 days. Lipid peroxide levels and acetylcholine esterase activity in brain tissues were slightly decreased at a dose dependent manner, in vitro. Lipid peroxide levels were also decreased at a dose dependent manner; methanolic extracts of Stachys sieboldii MIQ demonstrated significant inhibitory effects, in vivo. Monoamine oxidase and xanthine oxidase activities were significantly inhibited in the brain tissues of experimental group compared to control group and the ratio of type conversion of xanthine oxidase were decreased.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.11
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• pp.1573-1579
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• 2010

This research was performed to determine the antioxidant activity, nitrite scavenging activity, and its inhibitory activity on angiotensin converting enzyme (ACE), xanthine oxidase, $\alpha$-glucosidase, and elastase of hot water extract from pine bud (WPB). Antioxidant activity of WPB was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and superoxide dismutase (SOD)-like activity. DPPH radical scavenging activity and SOD-like activity of WPB were remarkably increased in a dose-dependent manner, and were about 71.4 and 85.4% at 2 mg/mL, respectively. The xanthine oxidase and ACE inhibitory activities were about 70.9 and 51.9% at 2 mg/mL of WPB, respectively. Nitrite scavenging activity of WPB was about 59.1, 53.8, and 39.5% on pH 1.2, 3.0, and 6.0 at 2 mg/mL, respectively. The WPB also showed elastase and $\alpha$-glucosidase inhibitory effects. These results revealed that pine bud have strong antioxidant activity and positive effects on the inhibition of xanthine oxidase, ACE, and elastase.

• Archives of Pharmacal Research
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• v.17 no.2
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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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• v.42 no.3
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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.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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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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• v.16 no.1
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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.