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Cytoprotective effects of a tripeptide from Chinese Baijiu against AAPH-induced oxidative stress in HepG2 cells via Nrf2 signaling

Wu, Jihong, Sun, Baoguo, Luo, Xuelian, Zhao, Mouming, Zheng, Fuping, Sun, Jinyuan, Li, Hehe, Sun, Xiaotao, Huang, Mingquan
RSC advances 2018 v.8 no.20 pp. 10898-10906
antioxidant activity, antioxidants, enzymes, glutathione, health promotion, human cell lines, malondialdehyde, messenger RNA, oxidative stress, protective effect, protein synthesis
Antioxidant peptides have been widely reported, whereas the intracellular antioxidant activity of a tripeptide (Pro-His-Pro, PHP), which was newly isolated and identified from Chinese Baijiu in our previous study, are still poorly understood. This study investigated the protective effects of PHP on 2,2′-azobis (2-methyl-propanimidamidine) dihydrochloride (AAPH)-induced oxidative stress in HepG2 cells and the involved molecular mechanisms. Pretreatment with PHP suppressed the generations of reactive oxygen species (ROS), malondialdehyde (MDA) and oxidized glutathione (GSSG), prevented a decrease in reduced glutathione (GSH), and up-regulated the activities of cellular antioxidant enzymes. Moreover, PHP treatment stimulated the mRNA and protein expression levels of antioxidant enzymes and nuclear factor E2 related factor 2 (Nrf2). Meanwhile, PHP markedly reduced the level of Kelch-like ECH-associated protein 1 (Keap1), suggesting that PHP effectively activated Nrf2/antioxidant response element (ARE)-mediated activity. These findings provide the first molecular basis for the health-promoting effects of PHP to prevent AAPH-induced oxidative stress.