Excessive reactive oxygen species (ROS) accumulation is involved in the pathogenesis of liver fibrosis and damage, specifically in the developing embryo that is extremely sensitive to oxidative stress. Herein, a liver injury model in chick embryo was established by using 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH), which was used to investigate the effect of cyclo(-Phe-Phe) (CPP), a natural dipeptide found in foods and beverages. The results showed that CPP significantly alleviated AAPH-induced liver pathological damage, hepatic dysfunction and inhibited the excessive production of ROS in both chick embryo liver and HepG2 cells. Additionally, CPP increased the antioxidative activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), as well as elevated the level of glutathione (GSH), suggesting that CPP combating liver injury probably depends on its antioxidant capability. Mechanistically, CPP upregulated the mRNA and protein expression of heme oxyense-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1) in vivo and in vitro, along with promoting the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) while inhibiting its degradation through binding with Kelch-like ECH-associated protein 1 (Keap1). In conclusion, this study proposes a potential peptide drug for the treatment of hepatic damage induced by oxidative stress and also unravels its mechanism of action.

中文翻译：

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Cyclo(-Phe-Phe)通过激活Nrf2通路减轻鸡胚肝损伤

过量的活性氧 (ROS) 积累参与肝纤维化和损伤的发病机制，特别是在对氧化应激极其敏感的发育中胚胎中。在此，使用2,2-偶氮双（2-脒基丙烷）二盐酸盐（AAPH）建立鸡胚肝损伤模型，用于研究天然二肽环（-Phe-Phe）（CPP）的作用存在于食品和饮料中。结果表明，CPP显着减轻AAPH引起的肝脏病理损伤、肝功能障碍，抑制鸡胚肝脏和HepG2细胞中ROS的过量产生。此外，CPP 增加了谷胱甘肽过氧化物酶 (GPx) 和超氧化物歧化酶 (SOD) 的抗氧化活性，并提高了谷胱甘肽 (GSH) 的水平，表明 CPP 对抗肝损伤可能取决于其抗氧化能力。从机制上讲，CPP 上调血红素氧化酶 1 (HO-1) 和 NADPH 醌氧化还原酶 1 (NQO1) 的 mRNA 和蛋白质表达在体内和体外，促进核因子红细胞 2 相关因子 2 (Nrf2) 的易位，同时通过与 Kelch 样 ECH 相关蛋白 1 (Keap1) 结合抑制其降解。总之，本研究提出了一种潜在的肽药物用于治疗氧化应激引起的肝损伤，并揭示了其作用机制。