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

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...

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Main Authors: Maria Elisabetta Clementi, Beatrice Sampaolese, Francesca Sciandra, Giuseppe Tringali
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/9/6/473
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author Maria Elisabetta Clementi
Beatrice Sampaolese
Francesca Sciandra
Giuseppe Tringali
author_facet Maria Elisabetta Clementi
Beatrice Sampaolese
Francesca Sciandra
Giuseppe Tringali
author_sort Maria Elisabetta Clementi
collection DOAJ
description 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.
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spelling doaj.art-724f80605f4d445f970a018f4ac3719a2023-11-20T02:33:57ZengMDPI AGAntioxidants2076-39212020-06-019647310.3390/antiox9060473Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing ApoptosisMaria Elisabetta Clementi0Beatrice Sampaolese1Francesca Sciandra2Giuseppe Tringali3National 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, ItalyNational 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, ItalyNational 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, ItalyPharmacology 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, ItalyThe 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.https://www.mdpi.com/2076-3921/9/6/473punicalaginARPE-19 (human-RPE cell line)nuclear factor erythroid 2-related factor (Nrf2)heme oxygenase-1 (HO-1)NADPH quinone dehydrogenase-1 (NQO1)apoptosis
spellingShingle Maria Elisabetta Clementi
Beatrice Sampaolese
Francesca Sciandra
Giuseppe Tringali
Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing Apoptosis
Antioxidants
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
title Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing Apoptosis
title_full Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing Apoptosis
title_fullStr Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing Apoptosis
title_full_unstemmed Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing Apoptosis
title_short Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing Apoptosis
title_sort punicalagin protects human retinal pigment epithelium cells from ultraviolet radiation induced oxidative damage by activating nrf2 ho 1 signaling pathway and reducing apoptosis
topic 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
url https://www.mdpi.com/2076-3921/9/6/473
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