7种药物对醛糖还原酶的抑制作用

应用酶动力学抑制实验,观察了7种药物对牛睾丸纯化的醛糖还原酶的抑制作用,结果发现sorbinil,tolrestat,水飞蓟宾,黄连素酶抑制作用较强,其抑制常数分别为:1.08,0.12μmol/L;3.5,2.7μg/ml。另外我们认为,利用本实验建立的方法可以进行醛糖还原酶抑制剂的初步筛选。     

槲皮素等中药提取物对醛糖还原酶的抑制作用

对7种中药提取物醛糖还原酶抑制作用的筛选实验结果表明:槲皮素对大鼠晶体醛糖还原酶的抑制作用最强,IC₅₀为3.44×10^-7mol/L。     

续断等50种中药对猪晶体醛糖还原酶的抑制作用

分别将续断(Dipsacus japonicus Mip)等50种中药水提取液加入猪晶体醛糖还原酶(AR)反应体系中,测定AR的活性,发现续断、紫菀(Aster tataricus L.f.)对AR有较强抑制作用。IC_(50)分别为57μg/ml、102μg/ml。提示可能对糖性白内障有防治作用。     

二氢杨梅素对醛糖还原酶的抑制作用

目的:研究二氢杨梅素体外对醛糖还原酶(AR)的影响。方法:取正常SD大鼠晶状体制备醛糖还原酶,以依帕司他1×10-7mol/L为阳性对照,观察二氢杨梅素1.0×10-5、4.0×10-5、1.4×10-4、6.4×10-4mol/L四个浓度体外对醛糖还原酶的抑制作用。结果:随着二氢杨梅素浓度的增加,醛糖还原酶的活性逐渐降低,且呈一定的剂量-效应关系,在终浓度为6.4×10-4mol/L时,其对醛糖还原酶活性的抑制率为54.3%。结论:二氢杨梅素在体外有抑制醛糖还原酶的作用。     

鬼针草不同提取物对醛糖还原酶的抑制作用

为了从鬼针草中发现治疗糖尿病合并症的天然物质,对鬼针草5种不同提取物对人醛糖还原酶筛选实验结果表明：EtOAc提取物对人醛糖还原酶抑制作用最强。     

马齿苋不同提取部位对醛糖还原酶的抑制作用

目的:观察马齿苋不同提取部位对人醛糖还原酶活性的抑制作用。方法:应用体外酶动力学抑制实验,以槲皮素为阳性对照,比较其与马齿苋不同提取部位对人醛糖还原酶活性的抑制作用。结果:乙酸乙酯部位对人醛糖还原酶具有较强的抑制作用,其抑制率可达107.0%,明显优于阳性对照品槲皮素;此外发现乙酸乙酯部位通过硅胶柱层析分离得到的Frl、Fr2、Fr3三个部位及水提部位通过AB-8大孔吸附树脂柱层析分离得到的Fr7部位的抑制率也都高于阳性对照组槲皮素。结论:马齿苋的乙酸乙酯部位对人醛糖还原酶有明显的抑制作用。     

桂辛通对糖尿病鼠晶体醛糖还原酶及山梨醇的影响

为了观察桂辛通过糖尿病大鼠晶体醛糖还原酶（ＡＲ）活性及山梨醇（ＳＮＳ）含量的影响,并探讨其作用机理。我们采用链脲佐菌素（ＳＴＺ）糖尿病（ＤＭ）大鼠模型,给予中药桂辛通灌胃,并以氨基胍作对照,观察了中药桂辛通过大鼠晶体ＡＲ活性和ＳＮＳ含量的影响。结果,辛通治疗后,糖尿病大鼠晶体ＡＲ活性和ＳＮＳ含量明显降低。与未治疗糖尿病大鼠比较有显著性差异（Ｐ〈０．０１）。提示桂辛通能改善糖尿病大鼠晶体多元醇代谢,     

石斛酚对醛糖还原酶的抑制作用及其机制研究

目的 探讨石斛酚对醛糖还原酶(AR)的抑制作用及其机制.方法 采用紫外分光光度法表征石斛酚对AR的抑制作用及抑制类型;采用分子对接软件Syby17.3中的FlexX预测二者作用残基及结合方式.结果 石斛酚对AR的IC50=2.12 mmnol/L,抑制类型为非竞争性抑制,并呈显强烈的量-效关系;二者作用残基为Trp111,His110,Tyr48,Trp20,主要结合方式是疏水相互作用、氢键和范得华力.结论 石斛酚对AR活性表现出良好的抑制作用.     

复方血栓通胶囊主要成分对醛糖还原酶的抑制作用

目的:研究复方血栓通胶囊主要有效成分对醛糖还原酶的抑制作用。方法:从正常SD大鼠晶状体中提取醛糖还原酶,以槲皮素为阳性对照,在含有还原型辅酶Ⅱ(NADPH)、醛糖还原酶、DL-甘油醛的反应体系中,加入不同浓度的10种成分单体,通过340nm处光密度的下降值计算各成分的半抑制浓度(IC50)。结果:三七皂苷R1、人参皂苷Rg1、人参皂苷Rb1、人参皂苷Rd、丹酚酸B、丹参酮Ⅰ、隐丹参酮、黄芪甲苷、哈巴俄苷、槲皮素的IC50分别为:0.180、0.109、1.01、0.15、0.799、0.0652、0.0742、0.00385、0.315、0.205μmol/m L,人参皂苷Re无明显抑制作用。结论:复方血栓通胶囊主要有效成分对醛糖还原酶具有不同程度的抑制作用。     

20种天然降压化合物对醛糖还原酶抑制作用的研究

目的:筛选出具有醛糖还原酶抑制作用的防治高血压伴糖尿病的高效低毒的天然降压药物.方法:在构效分析的基础上查阅文献,利用体外酶动学方法测定醛糖还原酶(AR)活性,研究天然降压化合物对牛晶状体醛糖还原酶的抑制作用.结果:芥子碱硫氰酸盐、金丝桃苷、水飞蓟素、丹参酚酸、川芎嗪、黄连素、黄芩素、茶多酚对醛糖还原酶的抑制作用活性最强,IC50值分别为36.9、37.6、39.3、35.9、36.9、35.4、36.8、37.9和39.6 μmol/L.结论:高效低毒的天然降压药物具有较强的醛糖还原酶抑制作用,可以用来防治高血压伴糖尿病.     

Isoquinoline Alkaloids from Tinospora cordifolia Inhibit Rat Lens Aldose Reductase

The inhibitory activity of Tinospora cordifolia stem‐derived alkaloids was evaluated against lens aldose reductase (AR) isolated from male Wistar rats. Anticataract potential of the alkaloids of T. cordifolia was evaluated in vitro in rat lenses, considering the activity of normal rat lenses as 100%. The biologically active constituents of T. cordifolia extract were characterized as the isoquinoline alkaloids, jatrorrhizine, palmatine and magnoflorine, by spectral analysis. The inhibitory effects varied with all chemicals and concentrations used. The inhibitory concentration (IC₅₀) values of jatrorrhizine, palmatine and magnoflorine are 3.23, 3.45 and 1.25 µg/mL respectively. The concentration of maximum activity was selected for its effect on galactose‐induced polyol accumulation in vitro. The percentage inhibition of galactose‐induced polyol accumulation was 62.6, 58.8 and 27.7% in the presence of jatrorrhizine, palmatine and magnoflorine, respectively. Magnoflorine may be useful as lead compounds and new agents for AR inhibition. Copyright © 2012 John Wiley & Sons, Ltd.     

六味地黄丸对早期糖尿病肾病患者红细胞醛糖还原酶活性的影响

目的观察中药六味地黄丸对早期糖尿病肾病(DN)患者红细胞醛糖还原酶(AR)活性的抑制作用,以探讨六味地黄丸作为醛糖还原酶抑制剂防治DN的临床意义。方法选用我院诊断为早期DN且中医辨证为气阴两虚证的患者72例,按随机对照原则分为对照组(31例,常规治疗,即口服糖适平或注射胰岛素)和治疗组(41例,常规治疗加六味地黄丸),3个月为1个疗程,观察治疗前后DN的症状与体征;测定空腹血糖(FBG)、早餐后2小时血糖(2hPBG)、血胆固醇(TC)、甘油三酯(TG)、红细胞AR活性、尿白蛋白排泄率(UAER),血、尿β2-微球蛋白(β2-MG)的改善情况。结果(1)六味地黄丸可使DN患者的症状与体征改善;(2)六味地黄丸使红细胞AR活性受到抑制,明显低于对照组(P＜0．05);UAER,血β2-MG明显低于对照组(P＜0．05);(3)对血糖、血脂、平均动脉血压无明显影响(P＞0．05)。结论六味地黄丸可明显抑制早期DN红细胞AR活性,改善DN各项指标,有助于早期DN的治疗     

Aldose Reductase Inhibitors of Plant Origin

Diabetic complications are attributed to hyperglycaemic condition which is in turn associated with the polyol pathway and advanced glycation end products. Aldose reductase (AR) is the principal enzyme of polyol pathway which plays a vital role in the development of diabetic complications. AR inhibitory activity can be screened by both in vitro and in vivo methods. In vitro assays for AR enzyme are further classified on the basis of the source of enzyme such as rat lens, rat kidney, cataracted human eye lens, bovine eyes and human recombinant AR enzymes, whereas the in vivo model is based on the determination of lens galactitol levels. A number of synthetic AR inhibitors (ARIs) including tolrestat and sorbinil have been developed, but all of these suffer from drawbacks such as poor permeation and safety issues. Therefore, pharmaceutical companies and many researchers have been carrying out research to find new, potent and safe ARIs from natural sources. Thus, many naturally occurring compounds have been reported to have AR inhibitory activity. The present review attempts to highlight phytochemicals and plant extracts with potential AR inhibitory activity. It also summarizes the classes of compounds which have proven AR inhibitory activity. Phytochemicals such as quercetin, kaempferol and ellagic acid are found to be the most promising ARIs. The exhaustive literature presented in this article clearly indicates the role of plant extracts and phytochemicals as potential ARIs. Copyright © 2013 John Wiley & Sons, Ltd.     

In Vitro and In Vivo Inhibitory Activities of Four Indian Medicinal Plant Extracts and their Major Components on Rat Aldose Reductase and Generation of Advanced Glycation Endproducts

The polyol enzyme aldose reductase (AR) and advanced glycation endproducts (AGEs) play an important role in diabetic complications such as cataracts. The purpose of this study was to investigate four standardized plant extracts used for the treatment of diabetes and related diseases, and their principal components for AR inhibitory activity and to find out their influence in diabetic complications. Thus, Boswellia serrata Triana & Planch. (Burseraceae), Lagerstroemia speciosa (L.) Pers. (Lythraceae), Ocimum gratissimum (L.) (Lamiaceae) and Syzygium cumin (L.) Skeels. (Myrthaceae) and their respective major constituents, boswellic acid, corosolic acid, ursolic acid and ellagic acid, were studied for their inhibitory activity against rat lens AR, rat kidney AR, human recombinant AR and generation of AGEs. In addition, in vivo inhibition of lens galactitol accumulation by the major constituents of the plants in galactose‐fed rat has been studied. The results revealed that all the tested extracts and their active ingredients possess significant AR inhibitory actions in both in vitro and in vivo assays with urosolic acid showing the most potent effect. Furthermore, the study indicates the potential of the studied plants and their major constituents as possible protective agents against long‐term diabetic complications. Copyright © 2012 John Wiley & Sons, Ltd.     

醛糖还原酶对211首糖尿病中药复方作用的筛选研究

目的通过醛糖还原酶高通量模型对211首中药复方的筛选,寻找治疗糖尿病的科研配方。方法从猪晶状体中提取醛糖还原酶,通过测定340nm处光密度的下降速率,间接测定醛糖还原酶的活性的方法建立的高通量醛糖还原酶筛模型的筛选,比较211首方剂的6 630个制备样品对醛糖还原酶的抑制作用。结果其中4首方中5组制备样品对醛糖还原酶有特异性的抑制作用。结论中药复方应用醛糖还原酶高通量模型筛选评价,简便快捷,可以优选得到科研配方。     

中草药来源的醛糖还原酶抑制剂的研究进展

中草药作为天然产物,无明显不良反应且来源广泛,以中草药为来源的醛糖还原酶抑制剂其不良反应远低于化学合成及微生物来源的醛糖还原酶抑制剂,在有效阻止和延缓糖尿病并发症如:糖尿病肾病、血管病变、视网膜病变、外周神经病变方面显示了良好的应用前景。作者主要综述了中草药活性成分黄酮类化合物及其衍生物,如:槲皮素、水飞蓟素、葛根素、黄芩苷、黄连素等和一些中药复方制剂,如:参丹健胰丸、筋脉通、六味地黄丸等在抑制醛糖还原酶的活性、降低山梨醇含量等方面取得的研究进展,并对其在治疗糖尿病并发症方面的现状进行了阐述。     

中药有效成分对药物代谢酶的影响

目的 :综述近年来中药有效成分对药物代谢酶的影响的研究进展。方法 :查阅近年来国内外报道中药有效成分对药物代谢酶的影响的文献 ,进行分析、总结。结果 :黄酮及黄酮衍生物、呋喃香豆素化合物、贯叶连翘和丹参的有效成分等均可抑制或诱导药物代谢酶细胞色素P450、尿苷二磷酸 葡萄糖醛酸转移酶、谷胱甘肽S-转移酶 ,从而影响多种常用药物在体内、外的代谢。结论 :我们将中药与其他药物合用时要注意其代谢性相互作用。