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xanthine oxidase inhibitors from Archidendron clypearia(Jack.) I.C. Nielsen: Results from systematic screening of Vietnamese medicinal plants

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Asian Pacific Journal of Tropical Medicine 2017年第6期10卷 619-626页

作者： Nguyen Thuy Duong Pham Duc Vinh Phuong Thien Thuong Nguyen Thi Hoai Le Nguyen Thanh Tran The Bach Nguyen Hai Nam Nguyen Hoang Anh Department of Pharmacology Hanoi University of Pharmacy Department of Pharmaceutical Analysis and Standardization National Institute of Medicinal Materials Department of Pharmacognosy Hue University of Medicine and Pharmacy Institute of Marine Biochemistry Vietnam Academy of Science and Technology Institute of Ecology and Biological Resources Vietnam Academy of Science and Technology Department of Medicinal Chemistry Hanoi University of Pharmacy

Objective: To screen Vietnamese medicinal plants for xanthine oxidase(XO) inhibitory activity and to isolate XO inhibitor(s) from the most active plant. Methods: The plants materials were extracted by methanol. The active plant materials were fractionated using different organic solvents, including n-hexane, ethyl acetate, and n-butanol. Bioassay-guided fractionation and column chromatography were used to isolate compounds. The compounds structures were elucidated by analysis of spectroscopic data, including IR, MS, and NMR. Results: Three hundreds and eleven methanol extracts(CME) belonging to 301 Vietnamese herbs were screened for XO inhibitory activity. Among these plants, 57 extracts displayed XO inhibitory activity at 100 μg/m L with inhibition rates of over 50%. The extracts of Archidendron clypearia, Smilax poilanei, Linociera ramiflora and Passiflora foetida exhibited the greatest potency with IC_(50) values below 30 μg/m L. Chemical study performed on the extract of Archidendron clypearia resulted in the isolation of six compounds, including 1-octacosanol, docosenoic acid, daucosterol, methyl gallate, quercitrin and(-)-7-O-galloyltricetiflavan. The compound(-)-7-O-galloyltricetiflavan showed the most potent XO inhibitory activity with an IC_(50) value of 25.5 μmol/L. Conclusions: From this investigation, four Vietnamese medicinal plants were identified to have XO inhibitory effects with IC_(50) values of the methanol extracts below 30 μg/m L. Compound(-)-7-O-galloyltricetiflavan was identified as an XO inhibitor from Archidendron clypearia with IC_(50) value of 25.5 μmol/L.

关键词： xanthine oxidase Inhibitor Medicinal plants Vietnam

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Determination of inhibitory activity of Salvia miltiorrhiza extracts on xanthine oxidase with a paper-based analytical device

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Journal of Pharmaceutical Analysis 2021年第5期11卷 603-610页

作者： Xingchu Gong Jingyuan Shao Shangxin Guo Jingjing Pan Xiaohui Fan Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China

A novel paper-based analytical device(PAD)was prepared and applied to determine the xanthine oxidase(XOD)inhibitory activity of Salvia miltiorrhiza extracts(SME).First,polycaprolactone was 3D printed on filter paper and heated to form hydrophobic *** the modified paper was cut according to the specific *** reagents including XOD for the colorimetric assay were immobilized on two separate pieces of *** simply adding phosphate buffer,the reaction was performed on the double-layer *** results were obtained by analyzing the color intensity with the specialized device system(consisting of a smartphone,a detection box and sandwich plates).The 3Dprinted detection box was small,with a size of 9.0 cm×7.0 cm×11.5 *** component G performed well in terms of linearity and detection limits and thus was identified as the *** reaction conditions were optimized using a definitive screening ***,a 10%glycerol solution was found to be a suitable *** the stabilizer was added,the activity of XOD could be maintained for at least 15 days under 4℃ or-20℃ storage *** inhibitory activity of SME was investigated and compared to that of *** results obtained with the PAD showed agreement with those obtained with the microplate *** conclusion,the proposed PAD method is simple,accurate and has a potential for point-of-care *** also holds promise for use in rapid quality testing of medicinal herbs,intermediate products,and preparations of traditional Chinese medicines.

关键词： Paper-based analytical device(PAD) Point-of-care testing xanthine oxidase Salvia miltiorrhiza extract 3D printing

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Delphinidin-3-O-sambubioside: a novel xanthine oxidase inhibitor identified from natural anthocyanins

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Food Quality and Safety 2021年第1期5卷 83-92页

作者： Jiahong Xie Haoxin Cui Yang Xu Lianghua Xie Wei Chen Department of Food Science and Nutrition Zhejiang Key Laboratory for Agro-Food ProcessingZhejiang UniversityHangzhouChina Ningbo Research Institute Zhejiang UniversityNingboChina

Objectives:This study was conducted to investigate the xanthine oxidase(XO)inhibitory activities of 18 monomeric anthocyanins from berry fruits and roselle,and to illustrate the underlying mechanism of the most active anthocyanin *** and Methods:Eighteen monomeric anthocyanins were prepared and purified in our *** inhibitory properties of anthocyanins were investigated by in vitro inhibitory activity studies and fluorescence quenching studies;the inhibitory mechanism was explored through kinetic studies,fluorescence quenching studies,circular dichroism analysis and computational docking ***:XO inhibitory activities of anthocyanins were related to the structures of B rings and *** all the tested anthocyanins,delphinidin-3-O-sambubioside showed the most potent inhibitory activity with an IC_(50) of 17.1μmol/L,which was comparable to the positive control *** results revealed that delphinidin-3-O-sambubioside could spontaneously interact with XO and induce conformational *** docking study indicated that delphinidin-3-O-sambubioside could bind to XO with a proper orientation,stably formed π-π interactions and hydrogen bonds with key residues,thus preventing the substrate from entering the active ***:In brief,our study identified delphinidin-3-O-sambubioside as a potent XO inhibitor from natural anthocyanins,which is potentially applicable for prevention and treatment of hyperuricemia.

关键词： anthocyanins xanthine oxidase delphinidin-3-0-sambubioside molecular docking inhibitory mechanism

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Antihyperuricemic effect of mangiferin aglycon derivative J99745 by inhibiting xanthine oxidase activity and urate transporter 1 expression in mice

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Acta Pharmaceutica Sinica B 2018年第2期8卷 306-315页

作者： Zhizhen Qin Shoubao Wang Yihuang Lin Ying Zhao Shengqian Yang Junke Song Tao Xie Jinlong Tian Song Wu Guanhua Du Beijing Key Laboratory of Drug Target and Screening Research Department of New Drug R&D Institute of Materia Medica Chinese Academy of Medical Science and Peking Union Medical College

A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase(XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7 th day to induce hyperuricemia. Meanwhile, J99745(3, 10, and 30 mg/kg), allopurinol(20 mg/kg) or benzbromarone(20 mg/kg) were orally administered to mice for 7 days. On the 7 th day,uric acid and creatinine in serum and urine, blood urea nitrogen(BUN), malondialdehyde(MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin(H&E) staining. Hepatic XOD, renal urate transporter 1(URAT1), glucose transporter type 9(GLUT9), organic anion transporter 1(OAT1) and ATP-binding cassette transporter G2(ABCG2) were detected by Western blot and real time polymerase chain reaction(PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid(FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our resultssuggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent.

关键词： Antihyperuricemic effect Mangiferin aglycon Derivative xanthine oxidase Urate transporter 1

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Preparation of a xanthine Sensor Based on the Immobilization of xanthine oxidase on a Chitosan Modified Electrode by Cross-linking

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Chinese Journal of Chemistry 2012年第7期30卷 1601-1604页

作者：刘玉革李伟明魏长宾吕玲玲 South Subtropical Crops Research Institute Chinese Academy of Tropical Agricultural ScienceZhanjiangGuangdong 524091China

Here in this paper, xanthine oxidase （XOD） was immobilized onto the chitosan （CHT） modified electrode by a simple way of cross-linking with glutaraldehyde （GTD） and 3-aminopropyltriethoxysilane （KH）. The electrode displayed a sharp peak to the oxidation of xanthine at a potential about 0.67 V and the optimum of pH for determination was investigated. Under the optimum conditions, the biosensor fabricated on the KH/GTD/XOD/CHT modified electrode showed excellent response to the oxidation of xanthine within the range of 0.5 to 18 μmol/L with a low detection limit of 0.0215 μmol/L, a good stability and a high selectivity. The sensor can also be used for the determination of hypoxantbine. The electrochemical results indicated that the immobilized enzyme still retained its biological activity and this provided a new way for the construction of biosensors and determination of xanthine.

关键词： sensor xanthine oxidase chitosan cross-linking

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In vitro xanthine oxidase inhibitory properties of Flos Sophorae Immaturus and potential mechanisms

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Food Bioscience 2022年第3期47卷 964-974页

作者： Jun Li Yuhong Gong Jinwei Li Liuping Fan State Key Laboratory of Food Science & Technology Jiangnan University1800 Lihu AvenueWuxiJiangsu214122China School of Food Science and Technology Jiangnan University1800 Lihu AvenueWuxiJiangsu214122China Collaborat Innovat Ctr Food Safety & Qual Control Jiangnan University1800 Lihu AvenueWuxiJiangsu214122China Institute of Food Processing Technology Guizhou Academy of Agricultural SciencesGuiyang550006China

Flos Sophorae Immaturus (FSI) possessed potential xanthine oxidase (XO) inhibitory activity as a uric acid-lowing natural *** present work identified and quantified the free and bound polyphenols of FSI by *** determined the primary polyphenols with XO inhibitory effect and clarified their potential mechanisms by omission experiment,interaction assay,inhibition type,and fluorescence *** results revealed that nine polyphenols were detected in the free polyphenol extract and ten polyphenols were detected in the bound polyphenol ***,seven polyphenols were identified as XO inhibitors,including quercetin,kaempferol,isorhamnetin,rutin,hyperoside,protocatechuic acid,and quercitrin with the IC50 values of 0.03,0.11,0.07,5.62,11.48,22.13,and 367.82 mg/mL,but their inhibition stability was lower than 24 *** the content of quercetin (18.87 mg/g) was not the highest,it played a crucial role to the XO inhibitory effect of ***,kaempferol and isorhamnetin alone revealed the sub-additive effect with quercetin,while the combination of other polyphenols with quercetin generated the interference or antagonism ***,isorhamnetin,and kaempferol were mixed-type and competitive inhibitors,which significantly quenched the fluorescence intensity of ***,the binding processes of quercetin-XO,kaempferol-XO,and isorhamnetin-XO were spontaneous and endothermic,and the hydrophobic interaction was the key driving *** general,quercetin,kaempferol,and isorhamnetin in FSI can be used as potential XO inhibitors.

关键词： Polyphenols Flos sophorae immaturus xanthine oxidase Interaction analysis Inhibition stability Fluorescence quenching

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Effects of acupuncture at Shu,Yuan,and Mu acupoints on blood se-rum uric acid and xanthine oxidase levels in a rat model of gout and hyperuricemia

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Journal of Traditional Chinese Medicine 2017年第6期37卷 841-845页

作者： Wang Xinyi Liu Bingyun Wang Shan Sui Minghe Institute of Acupuncture and Tuina Beijing University of Chinese MedicineBeijing 100029China

OBJECTIVE: To investigate the effects of needling the Shu, Yuan, and Mu acupoints on serum uric acid(SUA), xanthine oxidase(XOD), and alkaline phosphatase(ALP) levels and the kidney index in a rat model of gout and ***: Fifty rats were randomly divided into five groups: blank, model, Shu-acupoint, Yuan-acupoint, and Mu-acupoint groups. A rat model of hyperuricemia was developed by intragastric administration of adenine and ethambutol. This experiment last for 90 d in total. Treatment groups underwent 3 courses of acupuncture. Each course involved a total of 10 interventions(one intervention every second day) with each intervention lasting15 min. There was a break for 10 d between courses. SUA and ALP were analyzed using an automatic biochemical analyzer and XOD was analyzed using ***: Compared with the blank group, SUA and XOD levels in the model group were significantly higher and the renal index significantly improved. Compared with the model group, SUA and XOD levels in the three treatment groups decreased and the renal index significantly *** the three treatment groups were compared,the Mu-acupoint group showed the greatest decreases in SUA and XOD levels, followed by the Yuan-acupoint group. There was no significant difference in kidney index among the three treatment groups. There was no significant difference in ALP levels among the ***: The three treatments showed significantly reduced SUA and XOD levels compared with the control groups, possibly suggesting reduced renal damage.

关键词： Hyperuricemia Uric acid xanthine oxidase Points,Shu Points,Yuan(Source) Points,front Mu

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Identifi cation of egg protein-derived peptides as xanthine oxidase inhibitors:virtual hydrolysis,molecular docking,and in vitro activity evaluation

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Food Science and Human Wellness 2022年第6期11卷 1591-1597页

作者： Zhipeng Yu Yaxin Cao Ruotong Kan Huizhuo Ji Wenzhu Zhao Sijia Wu Jingbo Liu David Shiuan School of Food Science and Engineering Hainan UniversityHaikou 570228China College of Food Science and Engineering Bohai UniversityJinzhou 121013China Lab of Nutrition and Functional Food Jilin UniversityChangchun 130062China Institute of Drug Discovery Technology Ningbo UniversityNingbo 315211China

The purpose of this study was to screen the xanthine oxidase(XO)inhibitory peptides from egg white proteins through virtual hydrolysis,in vitro activity validation,and molecular *** results demonstrated that tripeptide EEK from ovalbumin exhibited potent XO inhibitory activity with an IC50 value of 141μmol/*** molecular docking results showed that tripeptide EEK bound with the active center of XO via 3 carbon hydrogen bond interactions,2 salt bridges,5 conventional hydrogen bond interactions,and 4 attractive charge *** residues Glu802,Phe1009,and Arg880 may play key roles in the XO catalytic ***,the key intermolecular forces of inhibiting XO activity may be special type of hydrogen bonds including carbon hydrogen bond interactions and attraction charge *** novel tripeptide EEK is potential candidates for controlling hyperuricemia.

关键词： Egg protein-derived peptides Hyperuricemia Inhibitor mechanism Molecular docking xanthine oxidase

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Effect of TongFengNing Decoction on Uric Acid Levels and xanthine oxidase Activity in Hyperuricemia Rats

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TMR Modern Herbal Medicine 2018年第4期1卷 189-197页

作者： Jian-hui Wang Jie-mei Guo Bao-lin Li Fang-zhou Teng Ya-ju Zhu Jian-ping Lin Yan Xiao Xiao Mao Lu-lu Huang You-xin Su Fujian University of Traditional Chinese Medicine Fujian China. Fujian Health College Fujian China. The Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine Fujian China.

Objective To observe the effect of TongFengNing Decoction （TD） on uric acid levels, xanthine oxidase （XOD） activity, and XOD mRNA expression of hyperuricemia （HUA） model rats. Methods： 90 rats were randomly divided into 6 groups （n=15）, and the HUA model in all groups except the blank group was established by administering hypoxanthine （HX） by gavage and injecting potassium oxonate （OAPS） intraperitoneally. Rats in all TD groups and allopurinol group were administered multiple doses of TD and a single dose of allopurinol by gavage twice daily for 21 days, while the blank group and the model group were administered normal saline. On the 7th, 14th, and 21st days of drug intervention, serum uric acid （SUA）, urine uric acid （UUA）, intestinal uric acid （IUA）, as well as XOD activity and mRNA expression in the liver and small intestine were measured in randomly selected 5 rats of each group. Results： On the 14th and 21st days of intervention, all TD dose groups and the allopurinol group showed decreased SUA and IUA levels, increased UUA levels, as well as decreased XOD activity and mRNA expression in the liver and small intestine, compared with the model group （P 〈 0.05）. The low- and high-dose TD group and the allopurinol group showed increased SUA and IUA levels, as well as XOD activity and mRNA expression in the liver and small intestine, and decreased UUA levels, compared with the moderate-dose TD group （P〈0.05）. Upon extending the drug intervention time of each TD dose group, SUA and IUA levels, XOD activity, and XOD mRNA expression in the liver and small intestine decreased and UUA levels increased （P 〈 0.05）. Conclusion： TD reduces SUA levels in HUA model rats, which promotes uric acid excretion and inhibits XOD activity and XOD mRNA expression to reduce uric acid production. The reduction in uric acid level by the intermediate dose of TD was better than that by allopurinol and the low and high doses of TD.

关键词： TongFengNing Hyperuricemia xanthine oxidase Uric acid Traditional Chinese medicine

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Antihyperuricemic effect of mangiferin aglycon derivative J99745 by inhibiting xanthine oxidase activity and urate transporter 1 expression in mice

Antihyperuricemic effect of mangiferin aglycon derivative J9...

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第九届中国药理学会补益药药理专业委员会学术研讨会

作者： Zhizhen Qin Shoubao Wang Yihuang Lin Ying Zhao Shengqian Yang Junke Song Tao Xie Jinlong Tian Song Wu Guanhua Du Beijing Key Laboratory of Drug Target and Screening Research Department of New Drug R&D Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical College

A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase(XOD) inhibitor by previous in vitro *** study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice,and explore the underlying *** were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7 th day to induce ***,J99745(3,10,and 30 mg/kg),allopurinol(20 mg/kg) or benzbromarone(20 mg/kg) were orally administered to mice for 7 *** the 7 th day,uric acid and creatinine in serum and urine,blood urea nitrogen(BUN),malondialdehyde(MDA) content and XOD activities in serum and liver were *** changes in kidney were observed using hematoxylin and eosin(H&E) *** XOD,renal urate transporter 1(URAT1),glucose transporter type 9(GLUT9),organic anion transporter 1(OAT1) and ATP-binding cassette transporter G2(ABCG2) were detected by Western blot and real time polymerase chain reaction(PCR).The results showed that J99745 at doses of 10 and30 mg/kg significantly reduced serum urate,and enhanced fractional excretion of uric acid(FEUA).H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and ***,serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia *** consistence with the ability to inhibit XOD,J99745 lowered serum MDA content in hyperuricemia *** results suggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression,thus representing a promising candidate as an anti-hyperuricemia agent.

关键词： Antihyperuricemic effect Mangiferin aglycon Derivative xanthine oxidase Urate transporter 1

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