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Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing Apoptosis

1
National Research Council (CNR), Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” (SCITEC)—c/o Istituto di Biochimica e Biochimica Clinica Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
2
Pharmacology Section, Department of Health Care Surveillance and Bioethics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma—Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
Antioxidants 2020, 9(6), 473; https://doi.org/10.3390/antiox9060473
Received: 26 April 2020 / Revised: 25 May 2020 / Accepted: 29 May 2020 / Published: 2 June 2020
(This article belongs to the Special Issue Pharmacological and Clinical Significance of Heme Oxygenase-1)
The oxidative damage of the retinal pigment epithelium (RPE) is the early event that underlies the pathogenesis of maculopathies. Numerous studies have shown that punicalagin (PUN), a polyphenol present in pomegranate, can protect several cell types from oxidative stress. Our study aims to establish if PUN protects RPE from UV radiation-induced oxidative damage. We used an experimental model which involves the use of a human-RPE cell line (ARPE-19) exposed to UV-A radiation for 1, 3, and 5 h. ARPE-19 cells were pre-treated with PUN (24 h) followed by UV-A irradiation; controls were treated identically, except for UV-A. Effects of pre-treatment with PUN on cell viability, intracellular reactive oxygen species ROS levels, modulation of Nrf2 and its antioxidant target genes, and finally apoptosis were examined. We found that pre-treatment with PUN: (1) antagonized the decrease in cell viability and reduced high levels of ROS associated with UV-A-induced oxidative stress; (2) activated Nrf2 signaling pathway by promoting Nrf2 nuclear translocation and upregulating its downstream antioxidant target genes (HO-1 and NQO1); (3) induced an anti-apoptotic effect by decreasing Bax/Bcl-2 ratio. These findings provide the first evidence that PUN can prevent UV-A-induced oxidative damage in RPE, offering itself as a possible antioxidant agent capable of contrasting degenerative eye diseases. View Full-Text
Keywords: punicalagin; ARPE-19 (human-RPE cell line); nuclear factor erythroid 2-related factor (Nrf2); heme oxygenase-1 (HO-1); NADPH quinone dehydrogenase-1 (NQO1); apoptosis punicalagin; ARPE-19 (human-RPE cell line); nuclear factor erythroid 2-related factor (Nrf2); heme oxygenase-1 (HO-1); NADPH quinone dehydrogenase-1 (NQO1); apoptosis
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Clementi, M.E.; Sampaolese, B.; Sciandra, F.; Tringali, G. Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing Apoptosis. Antioxidants 2020, 9, 473.

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