Abstract

Resveratrol is a phytoalexin, stilbenoid compound with antioxidant properties attributable to its bioactive trans-resveratrol content. This study characterized the effects of over-the-counter (OTC) resveratrol nutritional supplements and a HPLC-purified resveratrol formulation, in human transmitochondrial age-related macular degeneration (AMD) retinal pigment epithelial (RPE) patient cell lines. These cell lines, which were created by fusing blood platelets obtained from dry and wet AMD patients with mitochondria-deficient (Rho0) ARPE-19 cells, had identical nuclei (derived from ARPE-19 cells) but different mitochondria that were derived from AMD patients. After resveratrol treatment, the levels of cell viability and reactive oxygen species production were measured. Results demonstrated that treatment with different resveratrol formulations improved cell viability and decreased reactive oxygen species generation in each AMD patient cell line. Although further studies are required to establish the cytoprotective potential of resveratrol under different physiological conditions, this novel study established the positive effects of OTC resveratrol supplements in macular degeneration patient cybrid cell lines in vitro.

Highlights

  • Resveratrol is a biologically active stilbenoid i.e., a plant polyphenolic compound, and is commonly found in grapes’ (Vitis vinifera) skin and seeds, red and white wine, Japanese knotweed (Polygonum cuspidatum), blueberries, cranberries, bilberries, cocoa, pistachios, and peanuts

  • The current study demonstrates the biological effects of resveratrol in age-related macular degeneration (AMD) retinal pigment epithelial (RPE) transmitochondrial cells in which the mitochondria are derived from AMD patients and the nuclei come from Rho0 ARPE-19 cell lines

  • In our recent work [8,9,10,11], the ‘mtDNA damage’ that the AMD RPE cybrid cells implicitly carry from the AMD patients has been extensively characterized and various endpoints measured in terms of mitochondrial and cellular health have revealed significant differences including epigenetic alterations, downregulation of mitochondrial transcription and replication genes, mtDNA fragmentation, and reduction in mtDNA copy numbers observed in AMD RPE cybrid cells compared to normal RPE cybrid cells

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Summary

Introduction

Resveratrol is a biologically active stilbenoid i.e., a plant polyphenolic compound, and is commonly found in grapes’ (Vitis vinifera) skin and seeds, red and white wine, Japanese knotweed (Polygonum cuspidatum), blueberries, cranberries, bilberries, cocoa, pistachios, and peanuts. Compared to the other varieties of wines, red wine has the highest resveratrol content because it is produced by crushing the grapes and leaving the skins in contact with the juice throughout the fermentation process. The Malbec grapes are thicker skinned and have higher concentration of resveratrol compared to the other varieties of red wine grapes [1]. Resveratrol is a phytoalexin, which is synthesized de novo by numerous plants, including vines, in response to pathogen infection. Resveratrol occurs in two isomeric forms namely trans-resveratrol and cis-resveratrol. Dihydro-resveratrol is a metabolite of both cis- and trans-resveratrol having a different molecular weight

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