WF-2421 is a novel aldose reductase inhibitor produced by Humicola grisea. WF-2421 was purified from the culture filtrate by successive ion exchange chromatography and the chemical structure was assigned to be alpha-formamido-5'-(2-formamido-1-hydroxyethyl)- beta,2',6-trihydroxy-3-biphenylpropanoic acid (1) on the basis of spectroscopic evidence. The IC50 value of WF-2421 was 3 x 10(-8) M again...

Aldose reductase inhibitors improve nerve biochemistry, function, and structure in diabetic animals and increase nerve conduction in diabetic patients. Nevertheless, it has been difficult to demonstrate a benefit from these agents in patients with clinically overt diabetic neuropathy. Direct measurement of the nerve tissue penetration and biochemical and biological potency of these compounds is...

Using a rat lens organ-culture model, the authors investigated whether PM could inhibit AGE formation in the diabetic lens. They measured lens AGEs and relevant biochemical mediators including glutathione and the activities of aldose reductase and glyoxalase in normal and diabetic rat lenses. The results of this study showed that PM failed to block cataract development. However, PM treatment wa...

A serious factor limiting the engineering of stress tolerance has been our ignorance about the function of stress-induced genes. A stress-activated novel aldose-aldehyde reductase was cloned from alfalfa. The ectopic expression of this gene in tobacco resulted in tolerance to oxidative stress and dehydration. Physiological analysis suggested that aldose reductase probably functions by reducing ...

BACKGROUND Sepsis is a systemic inflammatory response syndrome characterized by excessive production of inflammatory cytokines and cardiovascular collapse. Postreceptor signaling events that lead to stress responses and cytokine production are sensitive to redox changes and products of lipid peroxidation. METHODS AND RESULTS We tested the hypothesis that inflammatory signaling and cytokine ge...

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 ...

Oxidative stress and polyol pathway hypotheses are generally accepted in the etiology of diabetic complications. Recently, novel carboxymethylated pyridoindoles, structural analogues of the efficient chain-breaking antioxidant stobadine, were designed, synthesised and characterised as prospective aldose reductase inhibitors endowed with antioxidant activity. Of them (2-benzyl-2,3,4,5-tetrahydro...

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...

Molecular docking is a frequently used tool in computer-aided structure-based rational drug design. Flavonoids are a group of natural products which exhibits various biological and pharmacological activities. The primary objective of this study was to investigate the aldose reductase inhibitory activity of flavonoids using in silico docking studies. In this perspective, flavonoids like aromaded...