جستجوی مقالات مرتبط با کلیدواژه "aldose reductase" در نشریات گروه "پزشکی"
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Background & Objective
Aldose reductase plays an important role in chronic diabetes and can cause tissue complications. Controlling the activity of aldose reductase provides an important strategy in controlling the complications of diabetes. Flavonoids are important inhibitors of aldose reductase. This study aimed to investigate the inhibitory nature of flavonol compounds in fruits and plants on aldose reductase activity by bioinformatic methods.
Material & MethodsThis study was descriptive-analytical. First, the structure of flavonol compounds, Ranirestat, and enzymes were downloaded from ChemSpider and PDB databases, respectively. Ranirestat was used as the standard drug. The pharmacokinetic properties and toxicity of the compounds were predicted by Swiss ADME, Protox servers, and Toxtree2.5.4 software. Then, to interact the compounds with the enzyme structure, molecular docking was used to method AutoDock Tools 1.5.6. Finally, the results were analyzed using Discovery Studio 3.5 software.
ResultsThe results showed that all flavonol compounds were desirable in pharmacokinetic properties and lacked toxicity. All compounds were able to inhibit aldose reductase enzymes with different PDB codes. However, among these compounds, the combination of Rutin with average docking energy of 191.21 kcal/ mole (P-value <0.05) had stronger binding energy than the standard Ranirestat drug.
ConclusionFrom the results of this study, it can be concluded that among the selected flavonol compounds, the Rutin compound showed stronger inhibitory activity than other flavonol compounds due to its interaction with important amino acids in the active site of the enzyme. As a result, further study of this compound in vivo and in vitro environments can be used as a potential candidate to inhibit the enzyme aldose reductase and ultimately prevent chronic complications of diabetes.
Keywords: Aldose reductase, Flavonol compounds, Inhibitor, Molecular Docking -
زمینه و هدف
دیابت قندی با عوارض مختلف چشمی ،کلیوی، عصبی و تولید مثلی همراه است. فعالیت مسیر پلی ال که سبب احیای گلوکز به سوربیتول می گردد به دلیل افزایش فعالیت آنزیم های آلدوز ردوکتاز (AR) و سوربیتول دهیدروژناز (SDH) یکی از مکانیسم هایی است که در پیشرفت عوارض جانبی دیابت دخالت دارد. مهار آنزیم AR می تواند یکی از اهداف برای جلوگیری از عوارض دیابت باشد. هدف این مطالعه بررسی اثر عصاره اتانولی دارچین بر میزان SDH در سرم و ARدر عدسی چشم و بافت بیضه موش های دیابتی بود.
روش هااین مطالعه از نوع تجربی بوده که بر روی 25 سر موش آزمایشگاهی صحرایی نر ویستار انجام شد. حافظه اجتنابی غیرفعال توسط دستگاه شاتل باکس و تعادل حرکتی توسط دستگاه روتارود سنجیده شد. موش ها به طور تصادفی در 5 گروه، گروه 1 (سالین) گروه 2 سیتالوپرام (دوز 2 نانومول) گروه 3 سیتالوپرام (دوز 2 نانومول) + استروژن (دوز 1 نانومول) گروه 4 سیتالوپرام (دوز 2 نانومول) + پروژسترون (دوز 1 نانومول) و گروه 5 سیتالوپرام (دوز 2 نانومول) + استروژن (دوز 1 نانومول) + پروژسترون (دوز 1 نانومول) دریافت کردند و به هر هیپوکمپ راست یا چپ حجم 5/1 میکرولیتر تزریق شد.
یافته ها:
گروهی که سیتالوپرام دریافت کردند زمان تاخیر برای ورود به ناحیه تاریک و مجموع زمان حضور حیوان در اتاقک روشن افزایش یافته، نشان می دهد که سیتالوپرام حافظه اجتنابی غیرفعال را افزایش داده است (0/001 > p). هنگامی که سیتالوپرام همراه با هورمون های استروییدی تزریق درون هیپوکمپی شدند افزایش قابل توجهی در یادگیری و حافظه موش ایجاد شد (0/01 > p). در تست تعادل حرکتی قبل از تزریق اختلاف معنی داری در بین گروه ها مشاهده نشد. پس از دریافت دارو در زمان های 1، 3 و 24 ساعت تعادل حرکتی کاهش معنی داری نسبت به گروه کنترل دیده شد (0/01 > p).نتیجه گیری:
تزریق داخل هیپوکمپی سیتالوپرام باعث افزایش حافظه اجتنابی در موش های دریافت کننده این دارو می شود، از طرفی سیتالوپرام هنگامی که با استروژن و پروژسترون همراه می شود باعث کاهش تعادل می شود.
کلید واژگان: استروژن, پروژسترون, حافظه اجتنابی, سیتالوپرام, هیپوکمپBackground and aimsDiabetes mellitus is accompanied by many complications in eye, kidney, nervous, and reproduction systems. Polyol pathway is one of the mechanisms involved in the development of diabetic complications due to increased activity of aldose reductase (AR) and sorbitol dehydrogenase (SDH). Inhibiting AR can be a target to prevent diabetes complications. This study aimed to evaluate the effect of cinnamon hydroalcoholic extract (CE) on serum SDH level and AR in the lens and testis of diabetic rats.
MethodsForty-eight male rats were classified into six groups as control (vehicle), treatment control I & II (250 or 350 mg/kg/day of CE, respectively), diabetic control (vehicle), and treatment groups I & II (250 or 350 mg/kg/day of CE respectively). Rats treated for 30 days. Diabetes mellitus was induced by a single dose of streptozotocin. Serum SDH, and AR level in the lens and testis were measured.
ResultsDiabetes significantly increased the level of SDH and AR. Cinnamon extracts significantly reduced theAR level in the testis and lens and serum SDH in the treatment group compared to the DC group (P<0.0001). There was no significant difference between control groups.
ConclusionCinnamon extracts may ameliorate some complications of the chronic diabetes through decreasing the level of SDH and AR.
Keywords: Aldose reductase, Cinnamon, Diabetes, Sorbitol dehydrogenase -
Introduction
Diabetic retinopathy is a late stage complication in diabetic patients and one which dramatically affects quality of life. Persistent hyperglycemia results in sorbitol accumulation due to increased activity of aldose reductase (AR), which leads to changes in membrane permeability and leakage of glutathione (GSH) from the lens which in turn results in the development of cataract and retinopathy. Hence, the present study was designed to assess the effect of Tribulus terrestris on AR activity and GSH level in diabetic rat lens, random blood glucose, hemoglobin A1c (HbA1c) and insulin.
MethodsDiabetes mellitus was induced by intra-peritoneal (i.p) injection of streptozotocinnicotinamide (STZ-NA). Animals were divided into 5 groups including normal controls (NC) treated with saline, untreated diabetic controls (DC), T. terrestris (150 and 300 mg/kg) and glibenclamide (500 µg/kg) treated diabetic rats. After 16 weeks of treatment, the rats were sacrificed, the lens was removed through posterior approach and homogenate was prepared for AR activity estimation. The lens tissue homogenate was prepared in normal saline for the estimation of GSH. Blood glucose was estimated by glucometer, HbA1c by nephelometry and insulin by ELISA kit.
ResultsAR activity was significantly reduced (P<0.004) in T. terrestris (both doses) treated groups compared to untreated diabetic controls. GSH levels were found significantly higher (P<0.005) in treated groups than the ones in diabetic controls. Glucose, HbA1c and insulin were significantly improved (P<0.004) in plant extract treated groups when compared to untreated diabetic rats.
ConclusionTribulus terrestris aqueous extract may be useful as AR inhibitor. It also has antioxidant and antidiabetic activities and thereby might be capable of controlling the hyperglycemia induced tissue damage.
Keywords: Retinopathy, Diabetes mellitus, Aldose reductase, Glutathione, Tribulus terrestris -
مقدمه
چندین مسیر متابولیکی در ایجاد عوارض دیابت نقش دارند که یکی از آنها مسیر پلی ال است. آنزیم کلیدی این مسیر آلدوز ردوکتاز می باشد که تبدیل گلوکز به سوربیتول را کاتالیز می کند. از جمله مواردی که می تواند در پیشگیری و درمان عوارض دیابت موثر باشد، مهارکننده های آلدوز ردوکتاز می باشد.
هدفدر این مطالعه اثر فراکسیون های مختلف گیاه مریم نخودی بر فعالیت آنزیم آلدوز ردوکتاز بررسی شد.
روش بررسی50 عدد لنز چشم گاو از کشتارگاه تهیه و آنزیم آلدوز ردوکتاز با استفاده از روش Hyman-Kinoshita method تخلیص شد. فعالیت آنزیم در حضور غلظت های مختلف (1، 5، 10، 20 و 100 میکروگرم بر میلی لیتر) عصاره و فراکسیون های آلی گیاه مریم نخودی بررسی شد. میزان IC50 فراکسیون های مختلف برای خنثی سازی رادیکال آزاد DPPH نیز اندازه گیری شد. علاوه بر آن چون گروهی از مهارکننده های این آنزیم ترکیبات فنولی هستند میزان ترکیبات فنولی و فلاونوییدی این گیاه مورد بررسی قرار گرفت.
نتایجطبق نتایج به دست آمده بیشترین مقدار فنول و فلاونویید و پایین ترین میزان IC50 برای مهار آنزیم آلدوز ردوکتاز با مقدار 67/3 میکروگرم بر میلی لیتر مربوط به فراکسیون اتیل استاتی با بود مطالعات کینتیکی نشان داد که نوع مهار فراکسیون ها از نوع غیررقابتی بود.
نتیجه گیریبا توجه به این یافته ها با جداسازی ترکیبات موثر گیاه و تاثیر آنها بر فعالیت آنزیم آلدوزردوکتاز می توان در آینده از این گیاه برای پیشگیری و یا درمان عوارض مزمن دیابت استفاده کرد.
کلید واژگان: مریم نخودی, آلدوز ردوکتاز, فراکسیون اتیل استاتی, مسیر پلی الBackgroundSeveral metabolic pathways are involved in the complications of diabetes like polyol pathway. Aldose reductase (AR) is a key enzyme in the polyol pathway, which catalyzes the conversion of glucose to sorbitol. AR inhibitors are appropriate to prevent and treat the diabetes complications.
ObjectiveThis study was designed to investigate the effect of different fractions of Teucrium polium on the AR activity.
MethodsFifty cow’s eye lenses were prepared and AR enzyme was purified according to the Hyman-Kinoshita method. The enzyme activity in the presence of the crude extract and different fractions of Teucrium polium (1, 5, 10, 20 and 100 μg/ml) was measured. In addition, IC50 content of fractions was also measured for the neutralization of DPPH free radical. Since some AR inhibitors are phenolic compounds, the phenolic and flavonoid contents have been investigated.
ResultsResults showed that the highest phenol and flavonoid content and the lowest IC50 value (3.67 µg/ml) for AR inhibition were related to the ethyl acetate fraction. Line weaver-Burk plot showed that ethyl acetate fraction acts as a non-competitive enzyme inhibition.
ConclusionThus, T. polium can be proposed as a therapy to prevent or treat chronic complications of diabetes in the future.
Keywords: Teucrium polium, Aldose reductase, Ethyl acetate fraction, Polyol pathway -
BackgroundThe relationship between the high activity of aldose reductase (AR) and diabetic cataract formation has been previously investigated. The purpose of the present study was to determine the preventing effect of melatonin on streptozotocin (STZ)-induced diabetic cataract in rats.Methods34 adult healthy male Sprague-Dawely rats were divided into four groups. Diabetic control and diabetic駩媶觢 received a single dose of STZ (50 mg/kg, intraperitoneally), whereas the normal control and normal駩媶觢 received vehicle. The melatonin groups were gavaged with melatonin (5 mg/kg) daily for a period of 8 weeks, whereas the rats in the normal control and diabetic control groups received only the vehicle. The rats eyes were examined every week and cataract formation scores (0-4) were determined by slit-lamp microscope. At the end of the eighth week, the rats were sacrificed and markers of the polyol pathway and antioxidative (Glutathione, GSH) in their lens were determined. The levels of blood glucose, HbA1c and plasma malondialdhyde (MDA), as a marker of lipid peroxidation, were also measured.ResultsMelatonin prevented STZ-induced hyperglycemia by decreased blood glucose and HbA1c levels. Slit lamp examination indicated that melatonin delayed cataract progression in diabetic rats. The results revealed that melatonin feeding increased the GSH levels, decreased the activities of AR and sorbitol dehydrogenase (SDH) and sorbitol formation in catractous lenses as well as plasma MDA content.ConclusionIn summary, for the first time we demonstrated that melatonin delayed the formation and progression of cataract in diabetic rat lenses.Keywords: Aldose reductase, Diabetes mellitus, Melatonin, Cataract, Sorbitol dehydrogenase
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BackgroundIncreased polyol pathway activity and subsequent occurrences, and particular sorbitol accumulation are noticed in the development of various secondary complications of diabetes. Aldose reductase (ALR2) or aldo-ketoreductase (AKR1B1) as the first and rate limiting enzyme of this pathway is a good target for new drugs for diabetes complications. A good inhibitor should inhibit aldehyde reductase (ALR1), the other member of this family lesser than ALR2. Bee propolis is a known substance in ancient medicine, but its effect on polyol pathway is unknown.ObjectivesThe current study aimed to investigate the effect of hydroalcoholic extract of propolis (HAEP) on partial purified bovine lens ALR2, also the effect of HAEP on sorbitol accumulation in human erythrocytes in high-glucose condition (ex vivo).Materials And MethodsTotal protein was determined by lowery method. Bovine lens ALR2 was partially purified by gel filtration chromatography on sephadexTM G25. Bovine cortex kidney ALR1 was partially purified by diethylaminoethyl (DEAE) precipitation. The hydroalcoholic extract was obtained from frozen propolis. The enzyme activity and sorbitol accumulation in erythrocytes were determined spectroflourimetrically.ResultsIt was found that ethyl acetate (EthAc) fraction (the more potent fraction) of HAEP inhibited ALR2 by IC50 value of 1.12 mg/mL up to 50% and this fraction can inhibit ALR2 8.25-fold greater than ALR1. In addition, it was found that this fraction could decrease sorbitol accumulation in human erythrocytes under high-glucose condition.ConclusionsThe obtained results indicated that propolis may be a good candidate for more studies to find new drugs for the treatment of secondary complications of diabetes.Keywords: Aldose Reductase, Aldehyde Reductase, Sorbitol, Propolis, Diabetes Complications
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