2-Chloro-1,4-naphthoquinone derivative of quercetin as an inhibitor of aldose reductase and anti-inflammatory agent

Abstract

The ability of flavonoids to affect multiple key pathways of glucose toxicity, as well as to attenuate inflammation has been well documented. In this study, the inhibition of rat lens aldose reductase by 3,7-di-hydroxy-2-[4-(2-chloro-1,4-naphthoquinone-3-yloxy)-3-hydroxyphenyl]-5-hydroxy-chromen-4-one (compound 1), was studied in greater detail in comparison with the parent quercetin (compound 2). The inhibition activity of 1, characterized by IC 50 in low micromolar range, surpassed that of 2. Selectivity in relation to the closely related rat kidney aldehyde reductase was evaluated. At organ level in isolated rat lenses incubated in the presence of high glucose, compound 1 significantly inhibited accumulation of sorbitol in a concentration-dependent manner, which indicated that 1 was readily taken up by the eye lens cells and interfered with cytosolic aldose reductase. In addition, compound 1 provided macroscopic protection of colonic mucosa in experimental colitis in rats. At pharmacologically active concentrations, compound 1 and one of its potential metabolite 2-chloro-3-hydroxy-[1,4]-naphthoquinone (compound 3) did not affect osmotic fragility of red blood cells.

Artichoke leaf extract, as AKR1B1 inhibitor, decreases sorbitol level in the rat eye lenses under high glucose conditions ex vivo

“…This reflects an increased flux of glucose through the polyol pathway. Similarly, threefold increase of sorbitol level in the eye lenses incubated with high glucose for 4 hr was observed in a previous study (Milackova et al, ). Sorbitol production (determined by fluorescent method) was significantly inhibited by all test samples (Art, ChA, and CA in two concentrations).…”

Restoration of density of interstitial cells of Cajal in the jejunum of diabetic rats after quercetin supplementation

“…Generally, the antioxidant properties of quercetin are attributed to its ability to act as: a) suppressor of the formation of reactive oxygen species by inhibition of the enzyme systems responsible for the generation of free radicals (including cyclooxygenase, lipoxygenase and xanthine oxidase) (38,39); b) for binding of superoxide anions, singlet oxygen and hydroxyl radicals, and as a consequence reducing lipid peroxidation (40); and c) its function as a chelating agent for transition metals such as iron and copper (41), preventing the catal-ysis of free radical production (38,39). In addition, quercetin is also considered to be an aldose reductase enzyme inhibitor (42). All these associated factors could contribute to the preservation of ICC in diabetic conditions.…”

Artichoke Leaf Extract Inhibits AKR1B1 and Reduces NF-κB Activity in Human Leukemic Cells

“…Aldose reductase from rat lenses (RL‐AKR) was partially purified using a procedure adapted from Hayman and Kinoshita () as previously described (Milackova et al, ). Briefly, after euthanasia, the lenses were quickly removed from the rats and homogenized in five volumes of cold distilled water in a glass homogenizer with a teflon pestle.…”