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 hours. 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.

中文翻译：

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葛根素通过激活Nrf2 / HO-1信号通路和减少细胞凋亡，保护人类视网膜色素上皮细胞免受紫外线辐射诱导的氧化损伤。

视网膜色素上皮（RPE）的氧化损伤是黄斑病变发病机理的早期事件。大量研究表明，石榴中存在的多酚punicalagin（PUN）可以保护多种细胞免受氧化应激。我们的研究旨在确定PUN是否能保护RPE免受紫外线辐射引起的氧化损伤。我们使用的实验模型涉及使用暴露于UV-A辐射1、3和5小时的人RPE细胞系（ARPE-19）。将ARPE-19细胞用PUN预处理（24小时），然后进行UV-A照射；除UV-A外，对照均进行相同处理。研究了PUN预处理对细胞活力，细胞内活性氧ROS水平，Nrf2及其抗氧化剂靶基因的调节以及最终凋亡的影响。我们发现用PUN进行预处理：（1）拮抗了与UV-A诱导的氧化应激相关的细胞活力的降低和高水平的ROS的降低；（2）通过促进Nrf2核易位并上调其下游抗氧化靶基因（HO-1和NQO1）来激活Nrf2信号通路；（3）通过降低Bax / Bcl-2比率诱导抗凋亡作用。这些发现提供了第一个证据，即PUN可以预防UV-A引起的RPE中的氧化损伤，从而使其自身成为可能与退化性眼病形成对比的抗氧化剂。（3）通过降低Bax / Bcl-2比率诱导抗凋亡作用。这些发现提供了第一个证据，即PUN可以预防UV-A诱导的RPE中的氧化损伤，使其成为可能与退化性眼病形成对比的抗氧化剂。（3）通过降低Bax / Bcl-2比率诱导抗凋亡作用。这些发现提供了第一个证据，即PUN可以预防UV-A诱导的RPE中的氧化损伤，使其成为可能与退化性眼病形成对比的抗氧化剂。