Abstract
(Poly)phenol-derived metabolites are small molecules resulting from (poly)phenol metabolization after ingestion that can be found in circulation. In the last decade, studies on the impact of (poly)phenol properties in health and cellular metabolism accumulated evidence that (poly)phenols are beneficial against human diseases. Diabetic retinopathy (DR) is characterized by inflammation and neovascularization and targeting these is of therapeutic interest. We aimed to study the effect of pyrogallol-O-sulfate (Pyr-s) metabolite in the expression of proteins involved in retinal glial activation, neovascularization, and glucose transport. The expression of PEDF, VEGF, and GLUT-1 were analyzed upon pyrogallol-O-sulfate treatment in RPE cells under high glucose and hypoxia. To test its effect on a diabetic mouse model, Ins2Akita mice were subjected to a single intraocular injection of the metabolite and the expression of PEDF, VEGF, GLUT-1, Iba1, or GFAP measured in the neural retina and/or retinal pigment epithelium (RPE), two weeks after treatment. We observed a significant decrease in the expression of pro-angiogenic VEGF in RPE cells. Moreover, pyrogallol-O-sulfate significantly decreased the expression of microglial marker Iba1 in the diabetic retina at different stages of disease progression. These results highlight the potential pyrogallol-O-sulfate metabolite as a preventive approach towards DR progression, targeting molecules involved in both inflammation and neovascularization.
Highlights
In the last decades, studies on the impact ofphenols in health and cellular metabolism have accumulated evidence thatphenols are beneficial against human diseases
We aimed to study the effect of pyrogallol-O-sulfate in retinal pigment epithelium (RPE) cells and in the diabetic retina, in the expression of molecules involved in DR-related neovascularization and retinal glial activation with the goal of assessing its potential in ameliorating diabetic retinopathy
To determine the effect of Pyr-s on retinal cells, we investigated the metabolic activity of RPE cells upon treatment with this metabolite
Summary
Studies on the impact of (poly)phenols in health and cellular metabolism have accumulated evidence that (poly)phenols are beneficial against human diseases. When trying to correlate the beneficial health effects described for dietary (poly)phenols and their bioavailability in humans, it is often observed that some of these compounds are poorly absorbed and may undergo several metabolic modification steps, including metabolism in the colon by the resident microbiota. Previous studies have shown the presence in human plasma of sulfated metabolites of pyrogallol in volunteers after ingestion of a fruit purée [6], which was found to reach concentrations up to 20 μM. Among the metabolites found in this study, concentrations of pyrogallol-O-sulfate (Pyr-s) were found to be significantly higher when compared to the baseline [6], raising some interest in their therapeutic value
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