Objective:To investigate the effects of a crude extract from Gnetum montanum Markgr.on ethanol-induced hepatotoxicity and metabolic disorders.Methods:Alcoholic liver disorder was induced in mice by administering incre...Objective:To investigate the effects of a crude extract from Gnetum montanum Markgr.on ethanol-induced hepatotoxicity and metabolic disorders.Methods:Alcoholic liver disorder was induced in mice by administering increasing doses of ethanol via oral gavage.Biomarkers of liver injury and oxidative stress were assessed at the end of the study.Liver tissue damage and fat deposition were evaluated using hematoxylin and eosin and oil red O staining,respectively.In addition,key biomarkers were examined in acetaldehyde-treated HepG2 cells.Results:Ethanol consumption induced characteristic pathological changes,including elevated serum markers of liver injury,hepatic lipid accumulation,and oxidative stress in liver tissues.Oral administration of Gnetum montanum extract(175 and 350 mg/kg)decreased serum aspartate aminotransferase,alanine aminotransferase,γ-glutamyl transferase,and bilirubin levels in ethanol-treated mice.The extract also lowered triglyceride levels in serum and liver tissue in a dose-dependent manner.Furthermore,it mitigated malondialdehyde levels,preserved reduced glutathione levels,and enhanced catalase activity and total antioxidant capacity in liver tissue homogenates.Additionally,ethanol-induced hyperuricemia was suppressed by Gnetum montanum extract by inhibiting xanthine oxidase activity.Similar effects were observed in Gnetum montanum extract-treated HepG2 cells.Conclusions:This study demonstrates that Gnetum montanum extract alleviates ethanol-induced hepatic injury by alleviating oxidative stress and inhibiting xanthine oxidase activity.展开更多
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 ac...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.展开更多
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 hy...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 hyperuricemia.METHODS: 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 immunofluorescence.RESULTS: 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 improved.When 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 groups.CONCLUSION: The three treatments showed significantly reduced SUA and XOD levels compared with the control groups, possibly suggesting reduced renal damage.展开更多
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 docking.The results demonstrated that t...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 docking.The results demonstrated that tripeptide EEK from ovalbumin exhibited potent XO inhibitory activity with an IC50 value of 141μmol/L.The 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 interactions.The residues Glu802,Phe1009,and Arg880 may play key roles in the XO catalytic reaction.Especially,the key intermolecular forces of inhibiting XO activity may be special type of hydrogen bonds including carbon hydrogen bond interactions and attraction charge interactions.The novel tripeptide EEK is potential candidates for controlling hyperuricemia.展开更多
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 a...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 barriers.Then the modified paper was cut according to the specific design.Necessary reagents including XOD for the colorimetric assay were immobilized on two separate pieces of paper.By simply adding phosphate buffer,the reaction was performed on the double-layer PAD.Quantitative 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 cm.Color component G performed well in terms of linearity and detection limits and thus was identified as the index.The reaction conditions were optimized using a definitive screening design.Moreover,a 10%glycerol solution was found to be a suitable stabilizer.When the stabilizer was added,the activity of XOD could be maintained for at least 15 days under 4℃ or-20℃ storage conditions.The inhibitory activity of SME was investigated and compared to that of allopurinol.The results obtained with the PAD showed agreement with those obtained with the microplate method.In conclusion,the proposed PAD method is simple,accurate and has a potential for point-of-care testing.It also holds promise for use in rapid quality testing of medicinal herbs,intermediate products,and preparations of traditional Chinese medicines.展开更多
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 ...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.展开更多
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 hyperu...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.展开更多
Acute pancreatitis(AP)is a potentially fatal condition with no targeted treatment options.Although inhibiting xanthine oxidase(XO)in the treatment of AP has been studied in several experimental models and clinical tri...Acute pancreatitis(AP)is a potentially fatal condition with no targeted treatment options.Although inhibiting xanthine oxidase(XO)in the treatment of AP has been studied in several experimental models and clinical trials,whether XO is a target of AP and what its the main mechanism of action is remains unclear.Here,we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP.We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models.We also found that allopurinol and febuxostat,as purine-like and non-purine XO inhibitors,respectively,exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points.Moreover,we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity.Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha(HIF-1α)-regulated lactate dehydrogenase A(LDHA)and NOD-like receptor family pyrin domain containing 3(NLRP3)signaling pathways and reduced the enrichment of^(13)C_(6)-glucose to^(13)C_(3)-lactate.Lastly,we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels,while pancreatic XO and urate were also increased in severe AP patients.These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.展开更多
Gout, as the second major metabolic disease after cardiovascular disease. Peptides have the advantages of natural and no side effects in the treatment and prevention of gout. This study aimed to screen xanthine oxidas...Gout, as the second major metabolic disease after cardiovascular disease. Peptides have the advantages of natural and no side effects in the treatment and prevention of gout. This study aimed to screen xanthine oxidase (XOD) inhibitory peptides from Scophthalmus maximus protein as a drug basis for the treatment of gout. The specific results are as follows: Immobilization of xanthine oxidase 25.564 μg/mg by modified magnetic beads, and modified magnetic beads can be reused three times. Three decapeptides (FSLVHYAGTV, FTNEKLQQFF and WDDMEKIWHH) were screened, the IC_(50) were 3.741, 4.046 and 2.203 mg/mL. Circular dichroism and three-dimensional fluorescence spectra showed that the inhibitory peptide would change the helical structure of XOD and the internal hydrophobic environment. Molecular docking showed that the inhibitory effect of inhibitory peptides depends on the number of unique amino acid residues in the active center of XOD enzyme. In conclusion, this study provides a method for screening anti-gout peptides, which not only solves the problem of treating gout, but also realizes the high-value utilization of marine products. In addition, this method has substantial application value because of its low cost and simple operation.展开更多
Flos Sophorae Immaturus (FSI) possessed potential xanthine oxidase (XO) inhibitory activity as a uric acid-lowing natural product.The present work identified and quantified the free and bound polyphenols of FSI by UPL...Flos Sophorae Immaturus (FSI) possessed potential xanthine oxidase (XO) inhibitory activity as a uric acid-lowing natural product.The present work identified and quantified the free and bound polyphenols of FSI by UPLC-QTOF-MS.Then determined the primary polyphenols with XO inhibitory effect and clarified their potential mechanisms by omission experiment,interaction assay,inhibition type,and fluorescence measurements.The results revealed that nine polyphenols were detected in the free polyphenol extract and ten polyphenols were detected in the bound polyphenol extract.Meanwhile,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 h.Although the content of quercetin (18.87 mg/g) was not the highest,it played a crucial role to the XO inhibitory effect of FSI.Furthermore,kaempferol and isorhamnetin alone revealed the sub-additive effect with quercetin,while the combination of other polyphenols with quercetin generated the interference or antagonism effects.Quercetin,isorhamnetin,and kaempferol were mixed-type and competitive inhibitors,which significantly quenched the fluorescence intensity of XO.Moreover,the binding processes of quercetin-XO,kaempferol-XO,and isorhamnetin-XO were spontaneous and endothermic,and the hydrophobic interaction was the key driving force.In general,quercetin,kaempferol,and isorhamnetin in FSI can be used as potential XO inhibitors.展开更多
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...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 delphinidin-3-O-sambubioside.Materials and Methods:Eighteen monomeric anthocyanins were prepared and purified in our laboratory.The 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 simulations.Results:XO inhibitory activities of anthocyanins were related to the structures of B rings and glycosides.Among 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 allopurinol.Spectroscopic results revealed that delphinidin-3-O-sambubioside could spontaneously interact with XO and induce conformational changes.Computational 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 pocket.Conclusions: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.展开更多
Heart failure is currently one of the most common and most cost-intensive of the chronic diseases The main cause of chronic heart failure （CHF） is the abnormalities of both cardiac contractile performance and myocar...Heart failure is currently one of the most common and most cost-intensive of the chronic diseases The main cause of chronic heart failure （CHF） is the abnormalities of both cardiac contractile performance and myocardial energy metabolism. Elevated levels of reactive oxygen species （ROS） have been proposed to contribute to both of them. Xanthine oxidoreductase （XO） is a major source of ROS in the cardiovascular system. XO inhibitors （XOIs） have been the cornerstone of the clinical management of gout and conditions associated with hyperuricemia for several decades.展开更多
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 elect...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.展开更多
In this study,SHECN(Ser-His-Glu-Cys-Asn)and SHCMN(Ser-His-Cys-Met-Asn)soybean peptides were used as the research objects to investigate their antioxidant activities and XO(xanthine oxidase)activity reduction effects.T...In this study,SHECN(Ser-His-Glu-Cys-Asn)and SHCMN(Ser-His-Cys-Met-Asn)soybean peptides were used as the research objects to investigate their antioxidant activities and XO(xanthine oxidase)activity reduction effects.The results show that SHECN and SHCMN have strong antioxidant activities,and at the same time protect the oxidative stress damage caused by HUA(hyperuricemia).They can quench XO,change the secondary structure of XO,and reduce its activity,which leads to the reduction of UA(uric acid)levels.Molecular docking demonstrated soybean peptides could bind to XO target proteins,respectively.In this study,SHECN and SHCMN were obtained from soybean peptides.Based on the data,soy peptides may be an attractive natural ingredient for the development of novel functional foods that inhibit XO activity.展开更多
An enzyme biosensor was constructed using a plate platinum electrode and immobilized xanthine oxidase (XOD). Only a very small quantity of enzyme was chemically immobilized on a special silk net. Hydrogen peroxide rel...An enzyme biosensor was constructed using a plate platinum electrode and immobilized xanthine oxidase (XOD). Only a very small quantity of enzyme was chemically immobilized on a special silk net. Hydrogen peroxide released during the enzymatic reaction was detected by the electrode at +0.65 V (vs. Ag/AgCl). The electrode was very sensitive to hypoxanthine and its detection limit was 1X10(-7) mol/L. When it was applied to the determination of fish freshness, the results agreed well with those obtained by traditional methods-determination of total volatile basic nitrogen (TVB-N) and microbial count. A range for estimating the freshness of river fish was suggested.展开更多
Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is ...Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid(UA) generation inhibitor in the 1950 s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target forvascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.展开更多
Objective To further investigate the neuroprotective effects of five isoflavonoids from Astragalus mongholicus on xanthine （XA）/xanthine oxidase （XO）-induced injury to PC12 cells. Methods PC12 cells were damaged b...Objective To further investigate the neuroprotective effects of five isoflavonoids from Astragalus mongholicus on xanthine （XA）/xanthine oxidase （XO）-induced injury to PC12 cells. Methods PC12 cells were damaged by XA/XO. The activities of antioxidant enzymes, MTT, LDH, and GSH assays were used to evaluate the protection of these five isofavonoids. Contents of Bcl-2 family proteins were determined with flow cytometry. Results Among the five isoflavonoids including formononetin, ononin, 9, 10-dimethoxypterocarpan-3-O-β-D-glucoside, calycosin and calycosin-7-O-glucoside, calycosin and calycosin-7-O-glucoside were found to inhibit XA/XO-induced injury to PC12 cells. Their ECs0values of formononetin and calycosin were 0.05 μg/mL. Moreover, treatment with these three isoflavonoids prevented a decrease in the activities of antioxidant enzymes, superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）, while formononetin and calycosin could prevent a significant deletion of GSH. In addition, only calycosin and calycosin-7-O-glucoside were shown to inhibit XO activity in cell-free system, with an approximate IC50 value of 10 μg/mL and 50 μg/mL. Formononetin and calycosin had no significant infuence on Bcl-2 or Bax protein contents. Conclusion Neuroprotection of formononetin, calycosin and calycosin-7-O-glucoside may be mediated by increasing endogenous antioxidants, rather by inhibiting XO activities or by scavenging free radicals.展开更多
OBJECTIVE: To evaluate the influence of the Tibetan medicine Ru Peng15 powder(RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models.METHODS: Hyperuricemic mice were g...OBJECTIVE: To evaluate the influence of the Tibetan medicine Ru Peng15 powder(RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models.METHODS: Hyperuricemic mice were generated by orally administering yeast extract paste twice daily(30 g/kg) for 8 days, to mimic human hyperuricemia induced by high-protein diets. Hyperuricemic rats were generated by intraperitoneal injection of 250 mg/kg potassium oxonate to each animal 1 h before the last oral administration of test compounds, which raised the serum uric acid level by inhibiting the decomposition of uric acid. Levels of uric acid and creatinine in serum and urine were detected by the phosphotungstic acid and picric acid methods respectively, and the activity of xanthine oxidase(XOD) was assayed using a commercial test kit.RESULTS: RPP15(0.4, 0.8, 1.2 g/kg) significantly decreased the level of serum uric acid in healthy rats(P < 0.05). Furthermore, hyperuricemic rats treated with RPP15(0.4, 0.8, 1.2 g/kg) had lower serum uric acid levels(P < 0.05), accompanied by lower urine uric acid(P < 0.05). For the hyperuricemic mice, the levels of uric acid in the serum decreased significantly(P < 0.05) and the activity of XOD in the liver was restored to normal levels after treatment with RPP15(P < 0.05).CONCLUSION: RPP15(0.4, 0.8, 1.2 g/kg) demonstrated an anti-hyperuricemic effect on both healthy and hyperuricemic animals, and the mechanism is most likely associated with inhibiting the activity of XOD.展开更多
AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in...AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in mice. METHODS: Mice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase (NOX) inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion. RESULTS: A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-α levels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure. CONCLUSION: Allopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generationof superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.展开更多
A new triterpene saponin with 28-nor-urs-12（13）,18（17）-dien-3β-ol as aglycone,named ilexsaponin C（1） was isolated from the roots of Ilex pubescens,together with three known saponins 2,3 and 4.The structure of 1...A new triterpene saponin with 28-nor-urs-12（13）,18（17）-dien-3β-ol as aglycone,named ilexsaponin C（1） was isolated from the roots of Ilex pubescens,together with three known saponins 2,3 and 4.The structure of 1 was elucidated on the basis of spectral analysis including 1D and 2D NMR and HR-ESI-MS.Saponins 1 and 4 exhibited significant XOD inhibitory activity in the test.展开更多
基金funded by Vietnam National Foundation for Science and Technology Development under grant number 108.05-2023.23.
文摘Objective:To investigate the effects of a crude extract from Gnetum montanum Markgr.on ethanol-induced hepatotoxicity and metabolic disorders.Methods:Alcoholic liver disorder was induced in mice by administering increasing doses of ethanol via oral gavage.Biomarkers of liver injury and oxidative stress were assessed at the end of the study.Liver tissue damage and fat deposition were evaluated using hematoxylin and eosin and oil red O staining,respectively.In addition,key biomarkers were examined in acetaldehyde-treated HepG2 cells.Results:Ethanol consumption induced characteristic pathological changes,including elevated serum markers of liver injury,hepatic lipid accumulation,and oxidative stress in liver tissues.Oral administration of Gnetum montanum extract(175 and 350 mg/kg)decreased serum aspartate aminotransferase,alanine aminotransferase,γ-glutamyl transferase,and bilirubin levels in ethanol-treated mice.The extract also lowered triglyceride levels in serum and liver tissue in a dose-dependent manner.Furthermore,it mitigated malondialdehyde levels,preserved reduced glutathione levels,and enhanced catalase activity and total antioxidant capacity in liver tissue homogenates.Additionally,ethanol-induced hyperuricemia was suppressed by Gnetum montanum extract by inhibiting xanthine oxidase activity.Similar effects were observed in Gnetum montanum extract-treated HepG2 cells.Conclusions:This study demonstrates that Gnetum montanum extract alleviates ethanol-induced hepatic injury by alleviating oxidative stress and inhibiting xanthine oxidase activity.
基金funded by Vietnam National Foundation for Science and Technology Development(NAFOSTED)under grant number 106.99-2012.90
文摘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.
基金Supported by Central Universities Fundamental Research Funds Project(Graduate Programs)from the Beijing University of Chinese Medicine:Experiment Research on the Effects of Acupuncturing Shu,Yuan,and Mu Acupoints in a Rat Model of Gout and Hyperuricemia(No.2015-JYB-XS127)
文摘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 hyperuricemia.METHODS: 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 immunofluorescence.RESULTS: 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 improved.When 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 groups.CONCLUSION: The three treatments showed significantly reduced SUA and XOD levels compared with the control groups, possibly suggesting reduced renal damage.
基金supported by Beijing Advanced Innovation Center for Food Nutrition and Human Health(20181036).
文摘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 docking.The results demonstrated that tripeptide EEK from ovalbumin exhibited potent XO inhibitory activity with an IC50 value of 141μmol/L.The 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 interactions.The residues Glu802,Phe1009,and Arg880 may play key roles in the XO catalytic reaction.Especially,the key intermolecular forces of inhibiting XO activity may be special type of hydrogen bonds including carbon hydrogen bond interactions and attraction charge interactions.The novel tripeptide EEK is potential candidates for controlling hyperuricemia.
基金The authors would like to thank the support of the National S&T Major Project of China(Grant No.:2018ZX09201011)the National Natural Science Foundation of China(Grant No.:81503242)the Fundamental Research Funds for the Central Universities(Grant No.:2018FZA7018).
文摘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 barriers.Then the modified paper was cut according to the specific design.Necessary reagents including XOD for the colorimetric assay were immobilized on two separate pieces of paper.By simply adding phosphate buffer,the reaction was performed on the double-layer PAD.Quantitative 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 cm.Color component G performed well in terms of linearity and detection limits and thus was identified as the index.The reaction conditions were optimized using a definitive screening design.Moreover,a 10%glycerol solution was found to be a suitable stabilizer.When the stabilizer was added,the activity of XOD could be maintained for at least 15 days under 4℃ or-20℃ storage conditions.The inhibitory activity of SME was investigated and compared to that of allopurinol.The results obtained with the PAD showed agreement with those obtained with the microplate method.In conclusion,the proposed PAD method is simple,accurate and has a potential for point-of-care testing.It also holds promise for use in rapid quality testing of medicinal herbs,intermediate products,and preparations of traditional Chinese medicines.
文摘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.
基金supported by National Natural Science Foundation of China(81573645,81202538 and 81673422)CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-3-007)National Science and Technology Major Projects for "Major New Drugs Innovation and Development"(2013ZX09508104and 2013ZX09402203)
文摘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.
基金supported by the National Natural Science Foundation of China(Dan Du,82170905)the Program of Science and Technology Department of Sichuan Province(Dan Du,2023NSFSC1755,China)+2 种基金the State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College(Dan Du,GTZK202107,China)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(Qing Xia,ZYJC18005,China)the West China,Nursing Discipline Development Special Fund Project,Sichuan University(Xia Li,HXHL21060,China).
文摘Acute pancreatitis(AP)is a potentially fatal condition with no targeted treatment options.Although inhibiting xanthine oxidase(XO)in the treatment of AP has been studied in several experimental models and clinical trials,whether XO is a target of AP and what its the main mechanism of action is remains unclear.Here,we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP.We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models.We also found that allopurinol and febuxostat,as purine-like and non-purine XO inhibitors,respectively,exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points.Moreover,we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity.Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha(HIF-1α)-regulated lactate dehydrogenase A(LDHA)and NOD-like receptor family pyrin domain containing 3(NLRP3)signaling pathways and reduced the enrichment of^(13)C_(6)-glucose to^(13)C_(3)-lactate.Lastly,we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels,while pancreatic XO and urate were also increased in severe AP patients.These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.
基金supported by the National Key Research and Development Program of China(2019YFD0901702)the Doctoral Startup Fund of Natural Science Foundation Program of Liaoning Province(2022-BS-301)the Basic Scientific Research Project of Education Department of Liaoning Province(Youth Project)(LJKQZ2021134).
文摘Gout, as the second major metabolic disease after cardiovascular disease. Peptides have the advantages of natural and no side effects in the treatment and prevention of gout. This study aimed to screen xanthine oxidase (XOD) inhibitory peptides from Scophthalmus maximus protein as a drug basis for the treatment of gout. The specific results are as follows: Immobilization of xanthine oxidase 25.564 μg/mg by modified magnetic beads, and modified magnetic beads can be reused three times. Three decapeptides (FSLVHYAGTV, FTNEKLQQFF and WDDMEKIWHH) were screened, the IC_(50) were 3.741, 4.046 and 2.203 mg/mL. Circular dichroism and three-dimensional fluorescence spectra showed that the inhibitory peptide would change the helical structure of XOD and the internal hydrophobic environment. Molecular docking showed that the inhibitory effect of inhibitory peptides depends on the number of unique amino acid residues in the active center of XOD enzyme. In conclusion, this study provides a method for screening anti-gout peptides, which not only solves the problem of treating gout, but also realizes the high-value utilization of marine products. In addition, this method has substantial application value because of its low cost and simple operation.
基金subsidized by the Jiangsu Key R&D plan,China(BE2019309)Construction Project of Innovative Talents Base of Guizhou Province([2016]22)which has enabled us to accomplish this study.
文摘Flos Sophorae Immaturus (FSI) possessed potential xanthine oxidase (XO) inhibitory activity as a uric acid-lowing natural product.The present work identified and quantified the free and bound polyphenols of FSI by UPLC-QTOF-MS.Then determined the primary polyphenols with XO inhibitory effect and clarified their potential mechanisms by omission experiment,interaction assay,inhibition type,and fluorescence measurements.The results revealed that nine polyphenols were detected in the free polyphenol extract and ten polyphenols were detected in the bound polyphenol extract.Meanwhile,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 h.Although the content of quercetin (18.87 mg/g) was not the highest,it played a crucial role to the XO inhibitory effect of FSI.Furthermore,kaempferol and isorhamnetin alone revealed the sub-additive effect with quercetin,while the combination of other polyphenols with quercetin generated the interference or antagonism effects.Quercetin,isorhamnetin,and kaempferol were mixed-type and competitive inhibitors,which significantly quenched the fluorescence intensity of XO.Moreover,the binding processes of quercetin-XO,kaempferol-XO,and isorhamnetin-XO were spontaneous and endothermic,and the hydrophobic interaction was the key driving force.In general,quercetin,kaempferol,and isorhamnetin in FSI can be used as potential XO inhibitors.
文摘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 delphinidin-3-O-sambubioside.Materials and Methods:Eighteen monomeric anthocyanins were prepared and purified in our laboratory.The 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 simulations.Results:XO inhibitory activities of anthocyanins were related to the structures of B rings and glycosides.Among 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 allopurinol.Spectroscopic results revealed that delphinidin-3-O-sambubioside could spontaneously interact with XO and induce conformational changes.Computational 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 pocket.Conclusions: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.
文摘Heart failure is currently one of the most common and most cost-intensive of the chronic diseases The main cause of chronic heart failure （CHF） is the abnormalities of both cardiac contractile performance and myocardial energy metabolism. Elevated levels of reactive oxygen species （ROS） have been proposed to contribute to both of them. Xanthine oxidoreductase （XO） is a major source of ROS in the cardiovascular system. XO inhibitors （XOIs） have been the cornerstone of the clinical management of gout and conditions associated with hyperuricemia for several decades.
基金Acknowledgement The work was supported by the Fund on Basic Scientific Research Project of Nonprofit Central Research Institutions （No. SSCRI200901） and the Natural Science Foundation of Hainan Province （No. 310099）.
文摘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.
基金This work was supported by the National Key Research and Development Program of China(2017YFD0400504).
文摘In this study,SHECN(Ser-His-Glu-Cys-Asn)and SHCMN(Ser-His-Cys-Met-Asn)soybean peptides were used as the research objects to investigate their antioxidant activities and XO(xanthine oxidase)activity reduction effects.The results show that SHECN and SHCMN have strong antioxidant activities,and at the same time protect the oxidative stress damage caused by HUA(hyperuricemia).They can quench XO,change the secondary structure of XO,and reduce its activity,which leads to the reduction of UA(uric acid)levels.Molecular docking demonstrated soybean peptides could bind to XO target proteins,respectively.In this study,SHECN and SHCMN were obtained from soybean peptides.Based on the data,soy peptides may be an attractive natural ingredient for the development of novel functional foods that inhibit XO activity.
基金Project supported by Zhejiang Provincial Natural Science Foundation and Instrumental Analysis Foundation of China.
文摘An enzyme biosensor was constructed using a plate platinum electrode and immobilized xanthine oxidase (XOD). Only a very small quantity of enzyme was chemically immobilized on a special silk net. Hydrogen peroxide released during the enzymatic reaction was detected by the electrode at +0.65 V (vs. Ag/AgCl). The electrode was very sensitive to hypoxanthine and its detection limit was 1X10(-7) mol/L. When it was applied to the determination of fish freshness, the results agreed well with those obtained by traditional methods-determination of total volatile basic nitrogen (TVB-N) and microbial count. A range for estimating the freshness of river fish was suggested.
文摘Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid(UA) generation inhibitor in the 1950 s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target forvascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.
基金supported by the Natural Science Foundation of China(No.NSFC.30670415).
文摘Objective To further investigate the neuroprotective effects of five isoflavonoids from Astragalus mongholicus on xanthine （XA）/xanthine oxidase （XO）-induced injury to PC12 cells. Methods PC12 cells were damaged by XA/XO. The activities of antioxidant enzymes, MTT, LDH, and GSH assays were used to evaluate the protection of these five isofavonoids. Contents of Bcl-2 family proteins were determined with flow cytometry. Results Among the five isoflavonoids including formononetin, ononin, 9, 10-dimethoxypterocarpan-3-O-β-D-glucoside, calycosin and calycosin-7-O-glucoside, calycosin and calycosin-7-O-glucoside were found to inhibit XA/XO-induced injury to PC12 cells. Their ECs0values of formononetin and calycosin were 0.05 μg/mL. Moreover, treatment with these three isoflavonoids prevented a decrease in the activities of antioxidant enzymes, superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）, while formononetin and calycosin could prevent a significant deletion of GSH. In addition, only calycosin and calycosin-7-O-glucoside were shown to inhibit XO activity in cell-free system, with an approximate IC50 value of 10 μg/mL and 50 μg/mL. Formononetin and calycosin had no significant infuence on Bcl-2 or Bax protein contents. Conclusion Neuroprotection of formononetin, calycosin and calycosin-7-O-glucoside may be mediated by increasing endogenous antioxidants, rather by inhibiting XO activities or by scavenging free radicals.
基金Supported by the National Natural Sciences Foundation of China(A Study on the Anti-gout Effects and Related Mechanisms of Tibetan Medicine Rupeng15 Powder,No.81160410)
文摘OBJECTIVE: To evaluate the influence of the Tibetan medicine Ru Peng15 powder(RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models.METHODS: Hyperuricemic mice were generated by orally administering yeast extract paste twice daily(30 g/kg) for 8 days, to mimic human hyperuricemia induced by high-protein diets. Hyperuricemic rats were generated by intraperitoneal injection of 250 mg/kg potassium oxonate to each animal 1 h before the last oral administration of test compounds, which raised the serum uric acid level by inhibiting the decomposition of uric acid. Levels of uric acid and creatinine in serum and urine were detected by the phosphotungstic acid and picric acid methods respectively, and the activity of xanthine oxidase(XOD) was assayed using a commercial test kit.RESULTS: RPP15(0.4, 0.8, 1.2 g/kg) significantly decreased the level of serum uric acid in healthy rats(P < 0.05). Furthermore, hyperuricemic rats treated with RPP15(0.4, 0.8, 1.2 g/kg) had lower serum uric acid levels(P < 0.05), accompanied by lower urine uric acid(P < 0.05). For the hyperuricemic mice, the levels of uric acid in the serum decreased significantly(P < 0.05) and the activity of XOD in the liver was restored to normal levels after treatment with RPP15(P < 0.05).CONCLUSION: RPP15(0.4, 0.8, 1.2 g/kg) demonstrated an anti-hyperuricemic effect on both healthy and hyperuricemic animals, and the mechanism is most likely associated with inhibiting the activity of XOD.
基金The National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), DK069939 the Technology Transfer Grant (TTG) by UC Davis Medical Center to Wu J
文摘AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in mice. METHODS: Mice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase (NOX) inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion. RESULTS: A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-α levels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure. CONCLUSION: Allopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generationof superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.
基金financially supported by the Postgraduate Innovation Project of Jiangsu Province,China(No. CX09B_284Z)
文摘A new triterpene saponin with 28-nor-urs-12（13）,18（17）-dien-3β-ol as aglycone,named ilexsaponin C（1） was isolated from the roots of Ilex pubescens,together with three known saponins 2,3 and 4.The structure of 1 was elucidated on the basis of spectral analysis including 1D and 2D NMR and HR-ESI-MS.Saponins 1 and 4 exhibited significant XOD inhibitory activity in the test.
