染料木素等5种黄酮类物质对小鼠血清尿酸水平及黄嘌呤氧化酶活性的影响

目的探讨黄酮类化合物染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶活性的影响,对正常小鼠血清和肝脏黄嘌呤氧化酶活性的影响,同时评价对小鼠血清尿酸水平的作用。方法采用改良的紫外分光光度法测定染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶的抑制作用,采用分光光度法研究对小鼠血清和肝脏黄嘌呤氧化酶活性的影响,以磷钨酸法测定对小鼠血清尿酸水平的作用。结果体外实验表明黄酮类化合物染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶活性无明显影响。体内实验观察到这5种黄酮类化合物能够显著升高或降低黄嘌呤氧化酶的活性;而且,血清尿酸水平与血清黄嘌呤氧化酶活性密切相关,与肝脏黄嘌呤氧化酶活性无明显关联。用这些黄酮类化合物给药的小鼠血清尿酸水平都高于正常对照组。结论这5种黄酮类化合物不能够作为替代别嘌醇的药物用来降低血清尿酸水平。     

染料木素、芹菜素、槲皮素、芦丁和落新妇苷对高尿酸血症小鼠黄嘌呤氧化酶活性及血清尿酸水平的影响

目的探讨黄酮类化合物染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶活性的影响,对高尿酸血症小鼠血清和肝脏黄嘌呤氧化酶活性的影响,同时评价对小鼠血清尿酸水平的作用。方法采用改良的紫外分光光度法测定染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶的抑制作用;采用尿酸酶抑制剂氧嗪酸钾诱导小鼠高尿酸血症模型,以分光光度法研究对小鼠血清和肝脏黄嘌呤氧化酶活性的影响,以磷钨酸法测定对小鼠血清尿酸水平的作用。结果体外实验表明这些黄酮类化合物对黄嘌呤氧化酶活性无明显影响。然而,体内实验观察到能够明显升高或降低黄嘌呤氧化酶的活性,而且,血清尿酸水平与血清黄嘌呤氧化酶活性密切相关,与肝脏黄嘌呤氧化酶活性无明显关联。该研究表明用这些黄酮类化合物给药的小鼠血清尿酸水平都高于正常对照组。结论这5种黄酮类化合物不能够作为替代别嘌醇的药物用来降低血清尿酸水平。     

Effects of Genistein, Apigenin, Quercetin, Rutin and Astilbin on serum uric acid levels and xanthine oxidase activities in normal and hyperuricemic mice

Flavonoids are widely found in plants and many of them possess biological and pharmacological activities. In the present study, we assessed the effects of the flavonoids Genistein, Apigenin, Quercetin, Rutin and Astilbin on xanthine oxidase (XO) activities in vitro, and in serum and the liver. The effects of the flavonoids on serum uric acid levels were also measured in vivo. In vitro studies indicated that the flavonoids tested did not significantly affect XO activity. However, significant increases and decreases in XO activities were observed in vivo. Moreover, serum XO activity was correlated with serum uric acid levels, while no correlation was observed for liver XO activity. The present study showed that serum uric acid levels in mice treated with the flavonoids tested here are higher than control levels. Therefore, the flavonoids tested here are not candidates for replacing Allopurinol as a treatment to reduce serum uric acid levels.     

Reducing effect of mangiferin on serum uric acid levels in mice

Context: Mangiferin, a natural bioactive xanthone C-glycoside, is widely present in medicinal plants like the leaf of Mangifera indica L. (Anacardiaceae). It has been reported that mangiferin possesses a variety of biological activities, including antidiabetic, hepatoprotective, anti-inflammatory, antioxidant, and anticarcinogenic. Objective: The hypouricemic effect and xanthine oxidoreductase (XOR) inhibitory activity of mangiferin were investigated here for the first time. Materials and methods: The hypouricemic effect of mangiferin was investigated in normal and hyperuricemic mice induced by potassium oxonate. Mangiferin at a dose of 0.75-100.0 mg/kg was given intragastrically to mice. The serum urate levels were determined using the phosphotungstic acid method. The hepatic activities of xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) in hyperuricemic mice were assayed using commercially available kits. Results: The results showed that mangiferin at a dose of 1.5, 3.0, and 6.0 mg/kg significantly reduced the serum urate levels (148.7 ± 37.8, 142.2 ± 44.5, 121.7 ± 21.7 μmmol/L) in hyperuricemic mice, compared with untreated hyperuricemic mice (201.8 ± 71.2 μmmol/L). However, mangiferin did not decrease the serum urate levels in normal mice until mangiferin was up to 100 mg/kg. In addition, the hepatic activities of XDH in hyperuricemic mice were significantly decreased by mangiferin, while no changes of XOD were observed. Acute toxicity study in mice showed that mangiferin was very safe at a dose of up to 25 g/kg. Discussion and conclusion: These findings demonstrate that mangiferin has the potential to be developed as a new therapeutic agent for the treatment of hyperuricemia and gout.     

Reducing effect of mangiferin on serum uric acid levels in mice

Context: Mangiferin, a natural bioactive xanthone C-glycoside, is widely present in medicinal plants like the leaf of Mangifera indica L. (Anacardiaceae). It has been reported that mangiferin possesses a variety of biological activities, including antidiabetic, hepatoprotective, anti-inflammatory, antioxidant, and anticarcinogenic.

Objective: The hypouricemic effect and xanthine oxidoreductase (XOR) inhibitory activity of mangiferin were investigated here for the first time.

Materials and methods: The hypouricemic effect of mangiferin was investigated in normal and hyperuricemic mice induced by potassium oxonate. Mangiferin at a dose of 0.75–100.0 mg/kg was given intragastrically to mice. The serum urate levels were determined using the phosphotungstic acid method. The hepatic activities of xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) in hyperuricemic mice were assayed using commercially available kits.

Results: The results showed that mangiferin at a dose of 1.5, 3.0, and 6.0 mg/kg significantly reduced the serum urate levels (148.7 ± 37.8, 142.2 ± 44.5, 121.7 ± 21.7 µmmol/L) in hyperuricemic mice, compared with untreated hyperuricemic mice (201.8 ± 71.2 µmmol/L). However, mangiferin did not decrease the serum urate levels in normal mice until mangiferin was up to 100 mg/kg. In addition, the hepatic activities of XDH in hyperuricemic mice were significantly decreased by mangiferin, while no changes of XOD were observed. Acute toxicity study in mice showed that mangiferin was very safe at a dose of up to 25 g/kg.

Discussion and conclusion: These findings demonstrate that mangiferin has the potential to be developed as a new therapeutic agent for the treatment of hyperuricemia and gout.     

Effects of uricosuric drugs and diuretics on uric acid excretion in oxonate-treated rats

A practical procedure for evaluating uricosuric agents was demonstrated using clearance experiments with potassium oxonate-treated rats. The fractional excretion value of uric acid showed a reabsorptive net flux of uric acid in the renal tubules of the animal, though the value was obviously higher than those of primates such as men, chimpanzees and cebus monkeys. However, the rats responded well to uricosuric drugs and diuretics. Probenecid and uricosuric diuretics such as tienilic acid induced hyperuricosuria due to the increase of fractional excretion of uric acid and/or the increase of the filtered amount of uric acid with the rise of plasma uric acid. On the other hand, furosemide had no effect on uric acid excretion at a low dose with moderate diuresis, while a higher dose decreased the fractional excretion of uric acid with elevation of plasma uric acid. Benzothiazides were also uricosuric at the lower doses, but the high dose, as in the case of the so-called uricosuric drugs, had no effect on the uric acid excretion and plasma uric acid level. Thus, oxonate-treated rats were useful for evaluating drug effects on uric acid excretion.     

高效液相色谱法定量尿酸、黄嘌呤和次黄嘌呤在人体血清中的浓度

目的:建立高效液相色谱法测定尿酸、黄嘌呤和次黄嘌呤在人体血清中的浓度.方法:用Agilent ZORBAX SB-Aq column色谱柱,ZORBAX-Extend C18预柱,以甲醇和47 mmol/LKH2PO4水溶液作为流动相,流速:1.0 mL/min,检测波长为260 nm.结果:血清中尿酸、黄嘌呤和次黄嘌呤的线性范围分别是(1.667～166.667)×103 ng/mL (r=0.9995)、(0.033～3.338)×103 ng/mL(r=0.9994)和(0.033～3.338)×103 ng/mL(r=0.9996),日间与日内精密度均＜15％.结论:该法灵敏度高,精密度和准确度佳,能满足非布司他体内药效学研究.     

Chronic ethanol consumption decreases serum sulfatide levels by suppressing hepatic cerebroside sulfotransferase expression in mice

Epidemiological studies demonstrate a possible relationship between chronic ethanol drinking and thrombotic diseases, such as myocardial infarction and stroke. However, the precise mechanism for this association remains unclear. Sulfatides are endogenous glycosphingolipids composed of ceramide, galactose, and sulfate, known to have anti-thrombotic properties. Low (0.5 g/kg/day), middle (1.5 g/kg/day), and high (3.0 g/kg/day) doses of ethanol were administered for 21 days intraperitoneally to female wild-type mice, and serum/liver sulfatide levels were measured. No significant changes in cholesterol and triglycerides were seen in serum and liver by ethanol treatment. However, serum/liver sulfatide levels were significantly decreased by middle- and high-dose ethanol treatment, likely due to downregulation of hepatic cerebroside sulfotransferase (CST) levels. Marked decreases in the expression of catalase and superoxide dismutases and ensuing increases in lipid peroxides were also observed in the livers of mice with middle- and high-dose ethanol treatment, suggesting the association between the suppression of hepatic CST expression and enhancement of oxidative stress. Furthermore, serum levels of tissue factor, a typical pro-coagulant molecule, were significantly increased in the mice with middle- and high-dose ethanol treatment showing decreases in serum sulfatide levels. Collectively, these results demonstrate that chronic ethanol consumption reduces serum sulfatide levels by increasing oxidative stress and decreasing the expression of CST in the liver. These findings could provide a mechanism by which chronic ethanol drinking increases thrombotic events.     

The methanol extract of Euonymus laxiflorus,Rubia lanceolata and Gardenia jasminoides inhibits xanthine oxidase and reduce serum uric acid level in rats

Chinese herbal medicinal plants, Euonymus laxiflorus (EL), Rubia lanceolata (RL) and Gardenia jasminoides (GJ), have been used wildly to treat arthritis and gout in Taiwan for decades. To understand the beneficial effects of these three plants, their xanthine oxidase (XO) inhibitory activity in vitro and hypouricaemic activity in vivo were investigated. Our results suggested that methanol extracts were better than water extracts for inhibition of XO activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, except the water extract of GJ, which exhibited the strongest radical scavenging effect. In animal study, the serum urate level was significantly decreased after oral administration of higher dose (0.39 g/kg) methanol extract of the mixture of three plants (ERG). In addition, methanol extract of ERG reduced the pain reaction time in the second phase of formalin induced pain. The results provide useful information on the pharmacological activities of these plants for the potential in treating hyperuricemia.     

痛风颗粒各部位对高尿酸血症大鼠尿酸和黄嘌呤氧化酶活性的影响

目的 通过观察痛风颗粒各部位对高尿酸血症大鼠血尿酸、尿尿酸、血黄嘌呤氧化酶活性和肝脏黄嘌呤氧化酶活性的影响,探讨其治疗痛风的物质基础和机制.方法 以腺嘌呤合乙胺丁醇法诱导大鼠高尿酸血症模型,分别用磷钨酸法和酶比色法检测尿酸和黄嘌呤氧化酶的含量.结果 黄酮类成分在降尿酸和抑制黄嘌呤氧化酶活性上均起主要作用;生物碱类成分对尿中尿酸的排泄和血清黄嘌呤氧化酶活性的抑制起较重要作用,有机酸类成分均未表现出明显作用;全方和有效部位组合有明显的降尿酸和抑制黄嘌呤氧化酶活性的作用.结论 黄酮类、生物碱和有机酸类有效部位组合后的药效与处方药一致,是该处方的有效部位群,对高尿酸血症模型大鼠表现出的降尿酸和抑制黄嘌呤氧化酶活性的作用最为显著.     

金苓痛风舒微丸对高尿酸血症小鼠血尿酸、肌酐、尿素氮及黄嘌呤氧化酶活性的影响

目的研究金苓痛风舒微丸对高尿酸血症小鼠的血尿酸(blood uric acid,BUA)、肌酐(creatinine,Cr)、尿素氮(blood urea nitrogen,BUN)、黄嘌呤氧化酶(xanthine oxidase,XOD)活性的影响,探讨其治疗痛风的机制。方法采用化学诱导剂氧嗪酸钾盐腹腔注射建立高尿酸血症小鼠模型,药物组分别灌服不同剂量金苓痛风舒微丸,1日1次,连续7d。末次给药1h后,取血,分离血清,采用ELISA法测定小鼠血清BUA、Cr和BUN;取肝脏组织检测XOD的活性。结果金苓痛风舒微丸高、中剂量能显著地降低高尿酸血症小鼠BUA、Cr和BUN的水平(P<0.01),高剂量显著抑制肝脏XOD的活性(P<0.01),中剂量也可明显降低XOD活性(P<0.05)。结论金苓痛风舒微丸的作用机制可能是通过增强肾血流量以及抑制尿酸的分解协同完成的。     

A single dose of rasburicase in elderly patients with hyperuricaemia reduces serum uric acid levels and improves renal function

Aim: Given the relevance of hyperuricaemia in the development of several diseases, we evaluated rasburicase, generally used in tumor lysis syndrome for uric acid treatment. Our purpose was to evaluate the reduction of serum uric acid and the improvement in renal function. Methods: This is a pilot randomized clinical trial. The study was performed as an 8-week, placebo-controlled group comparison of rasburicase and placebo. Thirty-eight patients were randomly assigned to administration of a single dose of rasburicase (4.5 mg in 100-cc physiological solution versus only physiological solution in 15 min). Results: We observed in the first week a fast decrease in uric acid value. Two months after rasburicase administration we saw a significant reduction of urate (p < 0.05) and creatinine (p < 0.001) and an increase in creatinine clearance (p < 0.001) and urate clearance (p < 0.001). Conclusion: In hyperuricaemic elderly patients, a single dose of rasburicase is very effective in lowering serum uric acid levels. Moreover, in patients treated with rasburicase we noted an improvement of renal function. We conclude that rasburicase is an alternative resource for treating those patients who are allopurinol intolerant, have renal dysfunction or have multiple polypharmacy problems in which drug–drug interaction may be of concern.     

儿童呼吸道感染疾病中血清尿酸、乳酸脱氢酶、α-羟丁酸脱氢酶的变化

目的研究儿童呼吸道感染病中血清尿酸(UA)、LDH(乳酸脱氢酶)、HBDH(α-羟丁酸脱氢酶)水平的变化与临床意义。方法根据发病原因不同,将100例呼吸道感染儿童分为细菌组、病毒组、支原体组;根据发病程度的不同,将100例呼吸道感染儿童分为肺炎组和上呼吸道感染组两组,利用AU680全自动生化分析仪检测100例呼吸道感染儿童发病期的UA、LDH、HBDH水平并与70例健康入园体检的儿童作对照,将肺炎组的UA、LDH、HBDH水平与上呼吸道感染组做比较。结果呼吸道感染的患儿发病期血清UA、LDH、HBDH水平均高于对照组(P 0.05),肺炎组患儿的UA、LDH、HBDH水平高于上呼吸道感染组(P 0.05)。结论血清UA、LDH、HBDH水平联合检验在小儿呼吸道感染中具有重要应用价值,能够协助判断患儿疾病感染程度及肺外并发心肌、肾脏损伤程度,指导临床医生的用药具有重要意义。     

Phloridzin reduces blood glucose levels and alters hepatic gene expression in normal BALB/c mice

We previously showed that a diet containing phloridzin suppressed the blood glucose levels in streptozotocin-induced diabetic mice most likely by inhibiting glucose absorption from the small intestine. In this study, we showed that 0.5% and 1% phloridzin diets significantly reduce the blood glucose levels in healthy normal BALB/c mice after 7 days of feeding. The 0.1% phloridzin diet did not suppress blood glucose levels but induced the alteration of the hepatic gene expressions related to carbohydrate and fatty acid metabolism in mice after 14 days. Ingenuity Pathway Analysis showed that 0.5% and 1% phloridzin diets suppressed the hepatic gene expressions related to the citrate cycle, gluconeogenesis, fatty acid metabolism, and valine, leucine, and isoleucine degradation in mice when compared with mice fed a control diet after 14 days. Thus the diet containing phloridzin reduces the blood glucose levels and the hepatic gene expressions associated with some metabolic functions in mice.     

奶及奶制品摄入降低痛风患者血尿酸水平

随着我国人民生活水平的不断提高,饮食结构与生活习惯发生改变,痛风发病率明显增高且发病年龄提前。饮食治疗是预防痛风的一个重要手段,科学合理的饮食可以防治和减少痛风的发作。近年来有研究显示,奶及奶制品的摄入对痛风有预防作用。本文就此作一简述。     

Montmorillonite adsorbs uric acid and increases the excretion of uric acid from the intestinal tract in mice

Objectives The aim was to evaluate the adsorbing effect of montmorillonite on uric acid, promoting diffusion of uric acid from blood to intestine, preventing absorption of uric acid in intestine and reducing uric acid level in serum. Methods The adsorbing effect of montmorillonite on uric acid was observed in vitro. The intestine and blood vessel of rats were circularly perfused with intestinal perfusate and vascular perfusate, respectively. A model of hyperuricaemia in mice was prepared by intraperitoneal injection of hypoxanthine and potassium oteracil. The concentration of uric acid was determined by the method of urate oxidase and peroxide enzyme. Key findings The results showed that different concentrations of montmorillonite could adsorb uric acid in a concentration‐dependent manner. The adsorbing effect was fast. The adsorptive rate was high in acid solution and was low in alkaline solution. When blood vessels were circularly perfused by vascular perfusate containing uric acid, the concentration of uric acid in vascular perfusate was decreased and the concentration of uric acid in intestinal perfusate was increased, suggesting that uric acid in blood vessels diffused into the intestine. When the intestine was perfused with intestinal perfusate containing uric acid, the uric acid concentration in vascular perfusate was increased, but the uric acid concentration of intestinal perfusate was decreased, suggesting that uric acid was absorbed in the intestine. The uric acid concentrations of intestinal perfusate and vascular perfusate in montmorillonite 0.5 and 1.0 g/kg groups were lower than the control group. Concentrations of uric acid in serum and urine in the montmorillonite 1 and 2 g/kg groups were lower compared with mice in the hyperuricaemic group. Conclusions The results suggested that montmorillonite adsorbed uric acid and promoted diffusion of uric acid from blood vessels to intestine, prevented absorption of uric acid in intestine and decreased uric acid level in serum.     

Black tea reduces uric acid and C-reactive protein levels in humans susceptible to cardiovascular diseases

The effect of black tea on the level of uric acid (UA) and C-reactive proteins (CRP) in humans susceptible to ischemic heart diseases was assessed in a prospective randomized controlled study. The study group consumed 9 g of black tea (equivalent to three cups of tea) daily for 12 weeks without additives followed by a 3-week wash-out (with control group consuming equivalent volume of hot water). Black tea consumption induced a highly significant decrease in the high uric acid baseline groups >6 mg/dL by 8.5%; p < 0.05. For men and women in the base line group >7 mg/dL, the decrease was 9.4% and 7.1%, respectively. In the low baseline serum uric acid levels there was a non-significant increase of 3.7% and 15% in men and women, respectively. C-reactive protein in the high risk group >3 mg/L was significantly decreased by 53.4% and 41.1% in men and women, respectively. For the non-supplemented group in this range the changes were 3.7% decrease for men and 2.9% increase for women. Tea supplementation-associated decrease in plasma uric acid and C-reactive protein levels may benefit humans at high risk of cardiovascular events and may augment drug therapy.     

高血压患者血尿酸水平变化与肾损害的关系

目的探讨高血压患者血尿酸(UA)浓度变化与肾脏损害的关系。方法随机选择126例高血压住院患者,分为高血压未发生肾损害组(n=58)、高血压早期肾损害组(n=41)、高血压临床肾损害组(n=27),以67例血压正常者作为对照,检测血清UA、肌酐(Cr)、尿素(Urea)和尿微量白蛋白(m-Alb)、尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG),进行比较分析。结果126例高血压患者的UA为(334.7±96.0)μmol/L,67例对照组UA为(226.4±54.6)μmol/L熏两组有显著性差异(t=8.526,P<0.001)。高血压组高UA血症发生率为24.60%,对照组高UA血症发生率为2.98%,两组有显著性差异(χ2=14.42,P<0.01)。高血压早期肾损害组血UA水平为(325.5±87.4)μmol/L,与高血压未发生肾损害组的穴323.4±85.9)μmol/L无显著性差异(t=0.119,P>0.05),高血压临床肾损害组UA(372.8±117.8)μmol/L明显高于高血压未发生肾损害组(t=2.165,P<0.05)。血UA与m-Alb、Urea呈正相关(r=0.209、0.593,P<0.05、P<0.01)。结论高血压患者血UA与肾脏损害存在着一定的关联,高血压并发明显肾损害是引起血UA增高的一个原因。