Recently we have developed novel oxotriazinoindole inhibitors (OTIs) of aldose reductase (ALR2), characterized by high efficacy and selectivity. Herein describe OTI derivatives design which is based on implementation additional intermolecular interactions within an unoccupied pocket the ALR2 enzyme. Four derivatives, OTI-(7–10), previously N-benzyl(oxotriazinoindole) inhibitor OTI-6 were synthe...

Herein, a series of twelve bis-hydrazone substituted isovanilline derivatives 3(a-l), were freshly re-synthesized by the reaction bis-aldehydes with hydrazide since these compounds previously showed potent aldose reductase inhibition properties. The obtained tested for their potential antibacterial and antioxidant activities. In present study, four different bacterial strains used, including Gr...

The aldose reductase (AR) inhibitor, 8-hydroxydaidzein, was isolated and identified from a methanolic extract of okara (soybean pulp) fermented with the fungal strain, Aspergillus sp. HK-388. 8-Hydroxydaidzein showed non-competitive inhibition of human recombinant AR with respect to DL-glyceraldehyde, its Ki value being evaluated as 7.0 microM.

We tested the hypothesis that the apoptosis of inner retina neurons and increased expression of glial fibrillary acidic protein (GFAP) observed in the rat after a short duration of diabetes are mediated by polyol pathway activity. Rats with 10 weeks of streptozotocin-induced diabetes and GHb levels of 16 +/- 2% (mean +/- SD) showed increased retinal levels of sorbitol and fructose, attenuation ...

The aim of this paper was to evaluate active principles for diabetic complications from Rhus verniciflua. Nine compounds were isolated via bioactivity guided fractionation and isolation and tested for their effects on recombinant human aldose reductase and advanced glycation endproducts. Butein and sulfuretin isolated from ethyl acetate fraction were found to possess strongly both forms of aldo...

Sorbitol (aldose reductase) pathway flux in diabetes perturbs intracellular metabolism by two putative mechanisms: reciprocal osmoregulatory depletion of other organic osmolytes e.g., myo-inositol, and alterations in NADPH/NADP+ and/or NADH/NAD+. The "osmolyte" and "redox" hypotheses predict secondary elevations in CDP-diglyceride, the rate-limiting precursor for phosphatidylinositol synthesis,...

This study was aimed at evaluating the potent and specific aldose reductase inhibitor fidarestat, on diabetes-associated cataract formation, and retinal oxidative-nitrosative stress, glial activation, and apoptosis. Control and streptozotocin-diabetic rats were treated with or without fidarestat (16 mg kg(-1)d(-1)) for 10 weeks after an initial 2-week period without treatment. Lens changes were...

The pomegranate, Punica granatum L., has been the subject of current interest as a medicinal agent with wide-ranging therapeutic indications. In the present study, pomegranate ethanolic seed and hull extracts were tested, in comparison with a commercial sample, for the inhibition of aldose reductase, an enzyme involved in the etiology of diabetic complications. In vitro inhibition of rat lens a...

The effects of D-xylose on the rat lens were studied using lens culture techniques. At 30 mM xylose a dramatic increase in lens water was accompanied by opacification of the lens. The osmotic change was apparently caused by the accumulation of xylitol and an increase in total electrolytes. All these changes were prevented from occurring when 1 mM of AY-22,284, an aldose reductase inhibitor, was...

AIMS The goal of the study was to evaluate the efficacy of epalrestat, an aldose reductase inhibitor, on diabetic retinopathy and diabetic nephropathy, based on analysis of the results of the Aldose Reductase Inhibitor-Diabetes Complications Trial, a 3-year multicentre comparative clinical trial of conventional therapy (control group) and epalrestat therapy (epalrestat group) in Japanese patien...