BACKGROUND Aldose reductase, the first enzyme of the polyol pathway, is the key determinant for the pathogenesis of long term diabetic complications. Accordingly, its inhibition represents the major therapeutic strategy to treat this kind of pathologies. OBJECTIVES In this work we describe the synthesis and the functional evaluation of a number of spiro-oxazolidinone and spiro-morpholinone ac...

Aldose reductase reduces glucose to sorbitol. It plays a key role in many of the complications arising from diabetes. Thus, aldose reductase inhibitors (ARI) have been identified as promising therapeutic agents for treating such complications of diabetes, as neuropathy, nephropathy, retinopathy, and cataracts. In this paper, a virtual screening protocol applied to a library of compounds in hous...

The aim of this study was to investigate aldose reductase inhibitory action of setipiprant as a potential additional mechanism contributing to its anti-inflammatory action. Aldose reductase activity was determined by spectrophotometric measuring of NADPH consumption. Setipiprant was found to inhibit aldose reductase/NADPH-mediated reduction of 4-hydroxynonenal, 4-hydroxynonenal glutathione and ...

Sorbitol production in the renal medulla increases in dehydrated rats, indicating that aldose reductase activity varies with the state of hydration. This response could be due to an increased synthesis of the enzyme (Moriyama T et al. J Biol Chem 1989:264:16810-16814) and/or a change in aldose reductase activity caused by acute changes in intracellular ionic composition, ionic strength, osmolal...

Sugar cataract formation has been demonstrated to result from lenticular sorbitol accumulation. In the lens, the activity of aldose reductase has been observed to increase with the onset of diabetes, while the activity of sorbitol dehydrogenase decreases. This shift in activities of these two Sorbitol Pathway enzymes favors the increased accumulation of sorbitol. Immunohistochemical studies wit...

Abstract Purpose The therapeutic use of oral hypoglycaemic agents in the management type-2 diabetes mellitus (T2DM) is without adverse effects; thus, calls for alternative and novel candidates from natural products medicinal plants. Method study explored molecular docking dynamics (MD) simulation approaches to identify key antidiabetic metabolites Crescentia cujete . Results Molecular results i...

In this work, isatin was employed as the scaffold to design aldose reductase inhibitors with antioxidant activity. Most of derivatives were proved be excellent in inhibition (ALR2) IC50 values at submicromolar level, and (E)-2-(5-(4-methoxystyryl)-2,3-dioxoindolin-1-yl) acetic acid (9g) identified most effective an value 0.015 μM. Moreover, compounds 9a–h styryl side chains C5 position showed p...