Excessive reactive oxygen species (ROS) promotes the oxidative stress of keratinocytes, eventually causing cell damage. The natural bromophenol bis (2,3,6-tribromo-4,5-dihydroxybenzyl) ether (BTDE) from marine red algae has been reported to have a varied bioactivity; however, its antioxidant effect has yet to be investigated systemically. Our present work aimed to explore the antioxidant effect of BTDE both on the molecular and cellular models and also to illustrate the antioxidant mechanisms. Our results showed that BTDE could effectively scavenge ABTS free radicals and protect HaCaT cells from damage induced by H₂O₂. Mechanism studies in HaCaT cells demonstrated that BTDE attenuated hydrogen peroxide (H₂O₂)-induced ROS production, reduced the malondialdehyde (MDA) level, decreased the oxidized glutathione (GSSG)/glutathione (GSH) ratio, and increased the antioxidant enzyme superoxide dismutase (SOD). Moreover, BTDE could inhibit the expression of Kelch-like epichlorohydrin-associated protein 1 (Keap1) and increase the expression of both nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream proteins TrXR1, HO-1, and NQO1. BTDE also activated the upstream signaling pathway of Nrf2 such as AKT pathway, while not activating the ERK or AMPKα pathways. In general, BTDE is a promising antioxidant to protect HaCaT cells against oxidative damage via Nrf2-mediated pathways.

中文翻译：

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Bromophenol Bis (2,3,6-Tribromo-4,5-dihydroxybenzyl) 醚通过 Nrf2 介导的途径保护 HaCaT 皮肤细胞免受氧化损伤

过量的活性氧（ROS）促进角质形成细胞的氧化应激，最终导致细胞损伤。据报道，来自海洋红藻的天然溴酚双（2,3,6-三溴-4,5-二羟基苄基）醚（BTDE）具有多种生物活性；然而，其抗氧化作用还有待系统研究。我们目前的工作旨在探索 BTDE 对分子和细胞模型的抗氧化作用，并说明抗氧化机制。我们的结果表明，BTDE 可以有效清除 ABTS 自由基并保护 HaCaT 细胞免受 H ₂ O ₂诱导的损伤。HaCaT 细胞的机制研究表明 BTDE 减弱过氧化氢（H ₂ O ₂) 诱导的 ROS 产生，降低丙二醛 (MDA) 水平，降低氧化型谷胱甘肽 (GSSG)/谷胱甘肽 (GSH) 比率，并增加抗氧化酶超氧化物歧化酶 (SOD)。此外，BTDE 可以抑制 Kelch 样表氯醇相关蛋白 1 (Keap1) 的表达，并增加核因子红细胞 2 相关因子 2 (Nrf2) 及其下游蛋白 TrXR1、HO-1 和 NQO1 的表达。BTDE 还激活了 Nrf2 的上游信号通路，如 AKT 通路，而不激活 ERK 或 AMPKα 通路。一般来说，BTDE 是一种很有前途的抗氧化剂，可通过 Nrf2 介导的途径保护 HaCaT 细胞免受氧化损伤。