丹参二萜醌对黄嘌呤氧化酶活性的抑制作用(英文)

目的黄嘌呤氧化酶(XOD)抑制剂对痛风或其他XOD诱导的疾病有潜在的治疗作用,因此探讨了从丹参(Salvia miltiorrhiza Bge.)中分离的丹参二萜醌---隐丹参酮(CT)和次甲丹参酮(MT)对XOD的抑制作用。方法在分子氧存在的条件下,XOD催化黄嘌呤产生尿酸和超氧阴离子。在黄嘌呤/XOD的反应媒介中加入CT或MT,通过测量波长290nm处吸光度的增加测定尿酸形成速率。结果CT和MT对XOD有抑制作用,酶动力学曲线Dixon图显示抑制方式是竞争型。CT和MT的Ki值分别为17.8和25.9μmol.L-1,抑制活性与浓度正相关。CT和MT的IC50值分别为70和67μmol.L-1,阳性对照别黄嘌呤醇的IC50值为60μmol.L-1。结论CT和MT对XOD活性有抑制作用,对痛风或其他XOD诱导的疾病可能有一定的治疗作用。     

黄嘌呤氧化酶抑制剂的研究进展

黄嘌呤氧化还原酶（Xanthine oxidoreductase,XOD)是一种高度通用的黄素酶,在不同物种之间以及生物各种组织中普遍存在。痛风是由于体内尿酸代谢障碍,导致尿酸水平过高,影响机体的正常运行。抑制黄嘌呤氧化还原酶可以降低尿酸水平,发挥抗高尿酸的作用。现如今临床上用于治疗痛风、高尿酸血症最有效的药物还是黄嘌呤氧化还原酶抑制剂。本文归纳了黄嘌呤氧化还原酶抑制剂的药理作用和临床应用,并对近年来已经上市和处于开发阶段的黄嘌呤氧化还原酶抑制剂进行总结,综述了黄嘌呤氧化还原酶抑制剂的最新进展。     

9种通络祛风中药提取物对黄嘌呤氧化酶的体外抑制活性研究

目的:研究9种通络祛风中药的提取物对黄嘌呤氧化酶(XO)的体外抑制活性,以筛选活性突出的中药提取物。方法:以黄嘌呤为底物、XO为反应酶,以别嘌醇为阳性对照,以三角风、石胡椒、山莓、金雀花根、紫藤根、牛迭肚根、梓木皮、凌霄花根、爬岩香等药材的水提物和甲醇提取物(以下简称"醇提物")以及活性提取物的石油醚、二氯甲烷、乙酸乙酯、正丁醇、水等萃取部位为对象,采用紫外分光光度法检测各样品对XO的抑制率,采用Graphpad prism 6.0软件计算半数抑制浓度(IC₅₀)以筛选活性提取物/部位;采用双倒数法判断药材的酶抑制作用的类型。结果:9种中药共18个提取物中,500μg/mL各中药提取物(除石胡椒醇提物外),250μg/mL三角风、石胡椒、山莓、爬岩香的水提物和醇提物,250μg/mL梓木皮水提物,250μg/mL金雀花根、牛迭肚根、凌霄花根醇提物,125μg/mL金雀花根、牛迭肚根醇提物以及62.5μg/mL金雀花根醇提物对XO的抑制率均超过了50%;其中,金雀花根醇提物的IC₅₀值为43.43μg/mL,低于其他药材的提取物,为活性提取物。...     

降尿酸药物黄嘌呤氧化酶抑制剂的研究进展

综述黄嘌呤氧化还原酶及黄嘌呤氧化酶抑制剂的研究进展,并对黄嘌呤氧化酶抑制剂的构效关系进行初步分析,为该类药物的深入研究提供参考。血中尿酸水平过高是痛风的第一大诱因,以黄嘌呤氧化酶抑制剂作为降尿酸药物,可以抑制黄嘌呤氧化酶的活性,减少体内尿酸的合成,从而达到治疗痛风的目的。     

痛风治疗药物及其研究进展

近年来,痛风的发病率呈上升的趋势,发病年龄也呈现低龄化的趋势,所以有关痛风的形成机制以及治疗药物的研发已成为人们关注的焦点。尿酸水平升高是痛风形成的生化基础,尿酸可介导血管炎症反应和氧化损伤、促进血管内皮细胞的增殖等,尿酸水平也是用来预测肾损伤的主要指标。本文对近些年来临床应用的治疗痛风的大部分药物,尤其是非嘌呤类黄嘌呤氧化酶抑制剂药物的研究进行综述。     

2-苯基-5-吡啶基-1,3,4-噁二唑类化合物的合成及黄嘌呤氧化酶抑制活性

目的 设计合成2-苯基-5-吡啶基-1,3,4-噁二唑类化合物,并对其黄嘌呤氧化酶抑制活性进行初步评价。方法 以对羟基苯甲酸甲酯为原料,经烃化、肼解、环合等反应合成目标化合物。以非布司他为阳性对照药,采用牛源的黄嘌呤氧化酶对目标化合物的抑制活性进行评价。结果 共合成了15 个未见文献报道的目标化合物,结构经核磁共振氢谱、飞行时间质谱和红外光谱确证。目标化合物均表现出一定的黄嘌呤氧化酶抑制活性,其中化合物 4m（IC₅₀=1.04 µmol·L^-1）活性最好,但低于阳性对照药非布司他（IC₅₀=0.024 µmol·L^-1）。结论 2-苯基-5-吡啶基-1,3,4-噁二唑类化合物作为新型黄嘌呤氧化酶抑制剂,其构效关系值得进一步研究。     

藏党参对黄嘌呤氧化酶活性的影响

目的研究藏党参及其提取物对黄嘌呤氧化酶活性的影响。方法以甲醇为溶剂制备藏党参的提取液,干燥;藏党参的提取物及分离纯化的单体以缓冲液稀释成不同浓度,采用紫外分光光度法测定其对黄嘌呤氧化酶活性的影响。结果藏党参的提取物及其分离纯化的单体对黄嘌呤氧化酶活性均有抑制作用并呈现较好的量效关系。结论藏党参对黄嘌呤氧化酶具有明显的抑制作用。     

虎杖不同溶剂提取物对黄嘌呤氧化酶的抑制作用与酶动力学研究

目的:研究虎杖不同溶剂提取物对黄嘌呤氧化酶的抑制作用与酶动力学。方法:质量浓度分别为200、100、50μg/ml的虎杖总提取物、石油醚提取物、乙酸乙酯提取物、正丁醇提取物、水提取物与120μl黄嘌呤氧化酶(0.02 U/ml)作用于240μl黄嘌呤溶液(300μmol/L),采用高效液相色谱(HPLC)法测定黄嘌呤氧化酶-黄嘌呤反应体系尿酸生成量,计算抑制率。以40、20、10、5μg/ml虎杖乙酸乙酯提取物与100、80、60、40μg/ml虎杖正丁醇提取物作用于240μl黄嘌呤溶液,采用HPLC法测定尿酸生成量。酶动力学研究采用双倒数作图法确定有效溶剂提取物的抑制类型,采用二次作图法求药物对游离酶的抑制常数(K)i、药物对酶底物络合物的抑制常数(Kis)。结果:质量浓度为200、100、50μg/ml时,虎杖乙酸乙酯、正丁醇提取物对黄嘌呤氧化酶的抑制率均大于50%;虎杖乙酸乙酯提取物的Ki和Kis分别为14.46、61.82μg/ml,虎杖正丁醇提取物的Ki和Kis分别为82.97、148.93μg/ml。结论:虎杖乙酸乙酯、正丁醇提取物对黄嘌呤氧化酶具有抑制作用,二者均为混合型抑制,对游离酶的抑制作用均强于对酶-底物复合物的抑制作用。该结论为虎杖治疗痛风的新药开发和抑制黄嘌呤氧化酶作用有效成分研究提供了依据。     

新型高效黄嘌呤氧化酶选择性抑制药非布斯坦

非布斯坦（febuxostat）是第一个全新型高效非嘌呤类黄嘌呤氧化酶选择性抑制药。于2009年2月13日经美国FDA批准上市,日本武田制药有限工司生产（商品名ULORIC。它是40年来首个获准治疗伴有高尿酸血症痛风患者的新药,与黄嘌呤相比,本品具有更高的安全性和有效性,     

TAP制药公司的新痛风治疗药前景良好

TAP制药公司的新黄嘌呤氧化酶抑制剂febuxo stat(TMX 6 7)Ⅱ期临床试验资料表明 ,该药对高尿酸血症引起的痛风是安全而有效的。最近在新奥尔良会议上 ,报道了 1 4 5名病人的临床试验结果 ,显示该药所有试用剂量 (4 0 ,80 ,1 2 0mg·d- 1)均能明显降低血清尿酸盐水平 ,4周治疗期间病人耐受性良好。代谢性血清尿酸盐升高 (>0 .4 4mmol·L- 1)引起痛风。由于尿酸产生过度或清除能力降低 ,尿酸盐结晶在病人组织中沉积 ,引起炎症性关节炎发作。血清尿酸盐必须低于 0 .4 4mmol·L- 1的水平 ,才能防止其在组织中沉积。黄嘌呤氧化酶是产生尿酸的…     

Therapeutic voyage of synthetic and natural xanthine oxidase inhibitors

Xanthine oxidase (XO) inhibitors are commonly used to treat gout, nephropathy, and renal stone diseases related to hyperuricemia. However, recent research has shown that these inhibitors may also have potential benefits in preventing vascular diseases, including those affecting the cerebrovasculature. This is due to emerging evidence suggesting that serum uric acid is involved in the growth of cardiovascular disease, and XO inhibition can reduce oxidative stress in the vasculature. There is a great interest in the development of new XO inhibitors for the treatment of hyperuricemia and gout. The present review discusses the many synthetic and natural XO inhibitors that have been developed which are found to have greater potency.     

Isolation and characterization of xanthine oxidase inhibitory constituents of Pyrenacantha staudtii

Six compounds have been isolated from the leaves of Pyrenacantha staudtii, two of which are new compounds.  The new compounds have been characterized as kaempherol 3-O-β-rhamnopyranosyl (1®6)- β-D-glucopyranoside (1) and 4-β-glucopyranosyl-(2-furyl)-5-methy-l,2-glucopyranoside phenylmethanone (2).  The known compounds are 3-pyridinecarboxylic acid (3), β-sitosterol (4), sitosterol 3-O-β-glucopyranoside (5) and taraxerol (6).  Their structures were determined by spectroscopic and chemical evidences.  The two new compounds together with 3-pyridinecarboxylic acid showed significant in vitro xanthine oxidase inhibitory activity.  To the best of our knowledge, this is the first report of these compounds from this plant.
     

Natural compounds with xanthine oxidase inhibitory activity: A review

Hyperuricemia (HUA), a disease due to an elevation of body uric acid level and responsible for various diseases such as gout, cardiovascular disorders, and renal failure, is a major ground debate for the medical science these days. Considering the risk factors linked with allopathic drugs for the treatment of this disease, the debate has now become a special issue. Previously, we critically discussed the role of dietary polyphenols in the treatment of HUA. Besides dietary food plants, many researchers figure out the tremendous effects of medicinal plants‐derived phytochemicals against HUA. Keeping in mind all these aspects, we reviewed all possible managerial studies related to HUA through medicinal plants (isolated compounds). In the current review article, we comprehensively discussed various bioactive compounds, chemical structures, and structure–activity relationship with responsible key enzyme xanthine oxidase.     

Febuxostat: a non-purine,selective inhibitor of xanthine oxidase for the management of hyperuricaemia in patients with gout

Febuxostat is a non-purine, selective inhibitor of xanthine oxidase being developed for the management of hyperuricaemia in patients with gout. With febuxostat 10 – 120 mg, the pharmacokinetics are linear. No dose adjustment appears to be necessary in those with renal insufficiency or mild-to-moderate hepatic impairment. Febuxostat 10 – 120 mg/day rapidly and sustainably reduces serum uric acid by 25 – 70% in uric acid underexcretors and overproducers. Prophylaxis with colchicine or a non-steroidal anti-inflammatory drug can mitigate the gout-flare risk from the rapid urate lowering after febuxostat initiation. Febuxostat is well tolerated, the majority of treatment-related adverse events are transient and mild-to-moderate in severity. Febuxostat can broaden the therapeutic options for urate-lowering therapy in those with gout.     

Antioxidant,antihyperuricemic and xanthine oxidase inhibitory activities of Hyoscyamus reticulatus

Context:?Xanthine oxidase (XO) is a key enzyme in the pathophysiological homeostasis of hyperuricemia. It catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid, the reaction involves the formation of free radical intermediates and superoxide byproducts.

Objectives:?This study was undertaken to investigate the antioxidant, antihyperuricemic, and xanthine oxidase inhibitory potentials of Hyoscyamus reticulatus L. (Solanaceae) extract.

Materials and methods:?The antioxidant potency was measured using the ABTS^?+ scavenging capacity system, which includes Trolox as a standard. The xanthine oxidase inhibitory activity of the extract was quantitated in vitro by measuring the decline in the catalytic rate of xanthine oxidase following incubations with the plant extracts and using xanthine as a substrate. The hypouricemic potential of the extract was evaluated using an in vivo model for hyperuricemia. We tested three different doses of the extract and allopurinol was used as standard antihyperuricemic positive control.

Results:?H. reticulatus aqueous extract exhibited significant antioxidant scavenging properties (533.26 μmol TE/g dry extract weight) and inhibitory effect on xanthine oxidase activity (IC₅₀ 12.8 μg/mL). Furthermore, oral administration of the aqueous extract significantly reduced serum urate levels in oxonate-induced hyperuricemic mice in a dose-dependent manner.

Discussion and conclusion:?Our results suggest that the aqueous extract of H. reticulatus aerial parts might have great potential as an antioxidant and a hypouricemic agent. Our lab is currently identifying the active compounds in the extract to which the biological activities could be attributed.     

以黄嘌呤氧化酶为靶点的新型非嘌呤类抗痛风及高尿酸血症药物研究进展

黄嘌呤氧化酶（XO）催化黄嘌呤生成尿酸及次黄嘌呤生成黄嘌呤的过程,是抗高尿酸血症或痛风药物研究的关键靶点。黄嘌呤氧化酶抑制剂由于作用机制明确、疗效显著而倍受关注,研发新型XO抑制剂具有广阔的应用前景。XO的结构生物学及分子模拟技术为新一代非嘌呤类XO抑制剂的合理药物设计奠定了基础。本文综述了以黄嘌呤氧化酶为靶标的新型非嘌呤类小分子杂环化合物及天然产物来源的活性分子在抗高尿酸血症或痛风药物研究领域中的进展。     

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。     

芬太尼对C6胶质瘤细胞黄嘌呤氧化还原酶基因表达的影响

<正> 芬太尼同吗啡是较强的μ受体激动剂,许多实验已经表明μ受体介导了吗啡的依赖、耐受作用。芬太尼是常用于心脑血管外科手术的麻醉镇痛剂。芬大尼在细胞水平对核苷酸代谢相关酶的基因表达还不清楚。本文采用了高度灵敏的RT-PCR-Southern杂交方法检测芬太尼对C6胶质瘤细胞黄嘌呤脱氢酶(Xanthine dehydrogenase,XD)/黄嘌呤氧化酶(Xanthine oxidase,XO)基因表达的影响。