OBJECTIVETo synthesize epalrestat and to improve the method of synthesis.

METHODSGlycine reacted with carbondisulfide,then with ClCH(2)COONa to give 3-carboxymethylrhodanine. PhCHO reacted with CH(3)CH(2)CHO in NaOH/EtOH solution to produce 2-methylcinnamaldehyde.3-carboxymethylrhodanine and 2-methylcinnamaldehyde were treated with NH(3).H(2)O to obtain epalrestat.

RESULTThe described method was effective in synthesis of Epalrestat and the yield was higher than that of in references.

CONCLUSIONThe results suggest that this method is suitable for industrial production.

Aldehyde Reductase ; antagonists & inhibitors ; Enzyme Inhibitors ; chemical synthesis ; Rhodanine ; analogs & derivatives ; chemical synthesis ; Thiazolidines

BACKGROUNDBerberine is one of the main constituents of Coptidis rhizoma (CR) and Cortex phellodendri. In this study, we investigated the beneficial effects of berberine on renal function and its possible mechanisms in rats with diabetic nephropathy (DN).

METHODSMale Wistar rats were divided into three groups: normal, diabetic model, and berberine treatment groups. Rats in the diabetic model and berberine treatment groups were induced to diabetes by intraperitonal injection with streptozotocin (STZ). Glomerular area, glomerular volume, fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Cr) and urine protein for 24 hours (UP24h) were measured using commercially available kits. Meanwhile, the activity of superoxide dismutase (SOD), content of malondialdehyde (MDA) in serum, activity of aldose reductase (AR) and the expression of AR mRNA and protein in kidney were detected by different methods.

RESULTSThe results showed that oral administration of berberine (200 mg x kg(-1) x d(-1)) significantly ameliorated the ratio of kidney weight to body weight. Glomerular area, glomerular volume, FBG, BUN, Cr and UP24h were significantly decreased in the berberine treatment group compared with the diabetic model group (P < 0.05). Berberine treatment significantly increased serum SOD activity and decreased the content of MDA compared with diabetic model group (P < 0.05). AR activity as well as the expression of AR mRNA and protein in the kidney was markedly decreased in the berberine treatment group compared with diabetic model group (P < 0.05).

CONCLUSIONThese results suggested that berberine could ameliorate renal dysfunction in DN rats through controlling blood glucose, reduction of oxidative stress and inhibition of the activation of the polyol pathway.

Aldehyde Reductase ; antagonists & inhibitors ; Animals ; Berberine ; pharmacology ; therapeutic use ; Diabetes Mellitus, Experimental ; complications ; Diabetic Nephropathies ; drug therapy ; Male ; Oxidative Stress ; drug effects ; Rats ; Rats, Wistar ; Streptozocin

OBJECTIVETo investigate the chemical compounds from the ethanol extract with inhibitory effects against aldose reductase from Thunbergia.

METHODGuided by anti-aldose reductase assay, compounds from the bioactive fraction (ethyl acetate extract) were separated and purified by various chromatographic methods including silica gel, Sephadex LH-20, and reversed-phase HPLC. Their structures were indentified based on analysis of the spectroscopic data including 1D and 2D NMR data.

RESULTEight compounds were obtained and identified as 8-hydroxy-8-methyl-9-methene-cyclopentane [7,11] -1,4, 6-trihydroxy-tetrahydronaphthalene-12-one, named as thunbergia A (1), 3,4-dihydro-4,5,8-trihydroxy-2-(3-methyl-2-butenyl) naphtha[2,3-b] oxiren-1(2H)-one (2), 8-(beta-gluco pyranosyloxy)-3,4-dihydro-2-(3-methyl-2-butenyl)naphtha [2,3-b] oxiren-1(2H)-one (3), galangin (4), quercetin (5), luteolin (6), 5,6,3',4'-tetrahydroxy -3,7-dimethoxy-flavone (7) and upeol (8).

CONCLUSIONThunbergia A was a new derivative of tetrahydronaphthalene, and compounds 2 and 3 were separated from the genus Thunbergia for the first time.

Acanthaceae ; chemistry ; Aldehyde Reductase ; antagonists & inhibitors ; Animals ; Nuclear Magnetic Resonance, Biomolecular ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; Plant Roots ; chemistry ; Rats

OBJECTIVETo study the anti-cataract effect of gigantol combined with syringic acid and their action mechanism.

METHODH202-induced lens oxidative injury in vitro rat model was establish to observe the impact of gigantol combined with syringic acid on lens transparency under a dissecting microscope. D-galactose-induced cataract rat model was established to observe the impact of gigantol combined with syringic acid on lens transparency under a slit-lamp. UV spectrophotometry was adopted to detect the inhibitory activity of gigantol combined with syringic acid against AR. Molecular docking method was used to detect binding sites, binding types and pharmacophores of gigantol combined with syringic acid in prohibiting aldose reductase.

RESULTBoth in vitro and in vivo experiments showed a good anti-sugar cataract activity in the combination of gigantol and syringic acid and a better collaborative effect than single component-gigantol and syringic acid and positive control drug Catalin. Molecular docking and dynamic simulation showed their collaborative AR-inhibiting amino acid residue was Asn160 and the major acting force was Van der Waals' force, which formed common pharmacophores.

CONCLUSIONGigantol combined with syringic acid shows good anti-cataract, their action mechanism is reflected in their good collaborative inhibitory effect on AR.

Aldehyde Reductase ; antagonists & inhibitors ; Animals ; Bibenzyls ; Cataract ; drug therapy ; enzymology ; Drug Synergism ; Female ; Gallic Acid ; analogs & derivatives ; pharmacology ; Guaiacol ; analogs & derivatives ; pharmacology ; Humans ; In Vitro Techniques ; Lens, Crystalline ; drug effects ; enzymology ; Male ; Rats ; Rats, Wistar

OBJECTIVETo study the effect of aldose reductase (AR) on expression of fibronectin and collagen IV in cultured rat renal mesangial cells (MsC).

METHODSAR expression plasmid vector (pCDNA3-AR) was constructed by restriction endonuclease digestion and ligation procedures. Stable expression of AR in MsC was established by Lipofectin transfection. Western blot and immunofluorescence analyses were performed to verify the transfection efficiency. Expression of fibronectin and collagen IV proteins were analyzed using Western blot.

RESULTSExpression of fibronectin and collagen IV in naive MsC treated with TGF-beta1 was upregulated in comparison to that of the untreated naive MsC (P < 0.01). MsC transfected with pCDNA3-AR showed a remarkable increase of expression of fibronectin and collagen IV (P < 0.01). Aldose reductase inhibitors (Sorbinil and Zopolrestat) significantly inhibited the expression of fibronectin and collagen IV in naive MsC (P < 0.05).

CONCLUSIONSOverexpression or inhibition of AR activity significantly alters the expression of fibronectin and collagen IV proteins in cultured rat MsC, suggesting that AR plays a significant role in the pathogenesis of glomerulosclersis.

Aldehyde Reductase ; antagonists & inhibitors ; genetics ; metabolism ; Animals ; Benzothiazoles ; pharmacology ; Cells, Cultured ; Collagen Type IV ; metabolism ; Fibronectins ; metabolism ; Genetic Vectors ; Imidazolidines ; pharmacology ; Mesangial Cells ; metabolism ; Phthalazines ; pharmacology ; Plasmids ; Rats ; Recombinant Proteins ; genetics ; metabolism ; Transfection ; Transforming Growth Factor beta1 ; pharmacology

OBJECTIVETo optimize the hydrolysis process of linarin by response surface methodology, and to use the model of aldose reductase to study the acacetin's activity of aldose reductase inhibitory.

METHODThe model of acacetin enzyme in vitro was established by the determination of fluorescence absorption of NADPH, the inhibition rate of acacetin aldose reductase was calculated, and then the IC50 of hydrolysis was obtained. The hydrolysis process of linarin hydrolysis condition was optimized by using response surface method.

RESULTThe results indicated that the IC50 of acacetin (2.74 mg x L(-1)) was less than the IC50 of linarin (3.53 mg x L(-1)). Hydrolyzation time of 7.4 h, sulphuric acid concentration of 0.54 mol x L(-1) and the ratio of material to liquid of 3 : 1 were the optimum conditions.

CONCLUSIONHydrolyzate acacetin has preferable inhibitory activity of aldose reductase. The optimized hydrolysis condition of linarin is convenient to use with good predictability.

Aldehyde Reductase ; antagonists & inhibitors ; metabolism ; Animals ; Diabetic Retinopathy ; enzymology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Enzyme Inhibitors ; chemistry ; pharmacology ; Flavones ; chemistry ; Glycosides ; chemistry ; pharmacology ; Glycosylation ; Humans ; Hydrolysis ; Male ; Rats ; Rats, Wistar ; Retina ; enzymology

OBJECTIVETo evaluate the aldose reductase inhibitory (ARI) activity of different fractions of Hybanthus enneaspermus for potential use in diabetic cataract.

METHODSTotal phenol and flavonoid content of different fractions was determined. ARI activity of different fractions in rat lens was investigated in vitro.

RESULTSThe results showed significant level of phenolic and flavonoid content in ethyl acetate fraction [total phenol (212.15±0.79 mg/g), total flavonoid (39.11±2.27 mg/g)] and aqueous fraction [total phenol (140.62±0.57 mg/g), total flavonoid (26.07±1.49 mg/g)] as compared with the chloroform fraction [total phenol (68.56±0.51 mg/g), total flavonoid (13.41±0.82 mg/g)] and petrolium ether fraction [total phenol (36.68±0.43 mg/g), total flavonoid (11.55±1.06 mg/g)]. There was a significant difference in the ARI activity of each fraction, and it was found to be the highest in ethyl acetate fraction [IC50 (49.26±1.76 µg/mL)] followed by aqueous extract [IC50 (70.83±2.82 µg/mL)] and it was least in the petroleum ether fraction [IC50 (118.89±0.71 µg/mL)]. Chloroform fraction showed moderate activity [IC50 (98.52±1.80 µg/mL)].

CONCLUSIONSDifferent fractions showed significanct amount of ARI activity, where in ethyl acetate fraction it was found to be maximum which may be due to its high phenolic and flavonoid content. The extract after further evaluation may be used in the treatment of diabetic cataract.

Aldehyde Reductase ; antagonists & inhibitors ; Animals ; Cataract ; drug therapy ; prevention & control ; Diabetes Complications ; drug therapy ; prevention & control ; Diabetes Mellitus ; pathology ; Flavonoids ; analysis ; Lens, Crystalline ; enzymology ; Phenols ; analysis ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar ; Violaceae ; metabolism

The traditional medicinal herbs are natural product, and have no obviously toxic action and side effect, and their resources are extensive. The adverse effects produced by aldose reductase inhibitors in traditional medicinal herbs are less than those from chemical synthesis and micro-organism, they can effectively prevent and delay diabetic complication, such as diabetic nephropathy, vasculopathy, retinopathy, peripheral neuropathy, and so on. They will have a wonderful respect. Flavonoid compounds and their derivates from traditional medicinal herbs are active inhibitors to aldose reductase, such as quercetin, silymarin, puerarin, baicalim, berberine and so on. In addition, some compound preparations show more strongly activity in inhibiting aldose reductase and degrading sorbitol contents, such as Shendan in traditional medicinal herbs being active inhibitors and Jianyi capsule, Jinmaitong composita, Liuwei Di-huang pill, et al. The progresses definite functions of treating diabetes complications have been reviewed.
Aldehyde Reductase ; antagonists & inhibitors ; metabolism ; Animals ; Diabetic Nephropathies ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Enzyme Inhibitors ; metabolism ; Humans ; Isoflavones ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Quercetin ; isolation & purification ; pharmacology ; Silymarin ; isolation & purification ; pharmacology

OBJECTIVEIsoliquiritigenin (ISL), a licorice chalconoid, is considered to be a bioactive agent with chemopreventive potential. This study investigates the mechanisms involved in ISL-induced apoptosis in human cervical carcinoma HeLa cells.

METHODSCell viability was evaluated using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Apoptosis was determined by flow cytometry using an Annexin V-FITC Apoptosis Detection Kit. The intracellular ROS levels were assessed using a 2, 7-dichlorofluorescein probe assay. The mitochondrial membrane potential was measured with the dual-emission potential-sensitive probe 5, 5', 6, 6'-tetra-chloro-1, 1', 3, 3'-tetraethyl-imidacarbocyanine iodide (JC-1). The degradation of poly-ADP-ribose polymerase (PARP) protein, the phosphorylation of PKR-like ER kinase (PERK), the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α), the expression of the 78 kD glucose-regulated protein (GRP 78), and the activation of caspase-12 were analyzed via western blot analysis.

RESULTSISL significantly inhibited the proliferation, the increase in ROS levels and apoptotic rates of HeLa cells in a concentration-dependent manner. Moreover, ISL induced mitochondrial dysfunction, caspase activation, and PARP cleavage, which displayed features of mitochondria dependent on apoptotic signals. Besides, exposure of HeLa cells to ISL triggered endoplasmic reticulum (ER) stress, as indicated by the increase in p-eIF2α and GRP78 expression, ER stress-dependent apoptosis is caused by the activation of ER-specific caspase-12.

CONCLUSIONThe findings from our study suggest that ISL-induced oxidative stress causes HeLa cell apoptosis via the mitochondrion-dependent and the ER stress-triggered signaling pathways.

Aldehyde Reductase ; antagonists & inhibitors ; Apoptosis ; drug effects ; Cell Survival ; drug effects ; Chalcones ; pharmacology ; therapeutic use ; Chemoprevention ; Drug Screening Assays, Antitumor ; Endoplasmic Reticulum Stress ; drug effects ; HeLa Cells ; Humans ; Mitochondria ; drug effects ; Neoplasms ; prevention & control ; Reactive Oxygen Species ; metabolism

Aldose reductase is a member of aldehyde-keto reductase superfamily widely existing in the kidney, adrenal gland, lens, retina, nerve, heart, placenta, brain, skeletal muscle, testis, blood vessels, lung, liver, et al. It is a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent enzyme catalyzing the reduction of various aldehydes and ketones to the corresponding alcohol. It is involved in many oxidative stress diseases, cell signal transduction and cell proliferation process as well as diabetes complications. In recent years, some progress has been made in research of the activity and gene regulation of aldose reductase and the relation with many common diseases.
Aldehyde Reductase ; antagonists & inhibitors ; metabolism ; physiology ; Animals ; Cell Proliferation ; Diabetes Complications ; drug therapy ; enzymology ; Enzyme Inhibitors ; therapeutic use ; Humans ; Oxidative Stress ; Rhodanine ; analogs & derivatives ; therapeutic use ; Signal Transduction ; Thiazolidines ; therapeutic use