title: Hesperetin protects against H2O2-triggered oxidative damage via upregulation of the Keap1-Nrf2/HO-1 signal pathway in ARPE-19 cells.
abstract: Age-related macular degeneration (AMD) is an irreversible vision loss disease that primarily results from oxidative stress that causes oxidative damage to the retinal pigment epithelial (RPE) cells. Hesperetin (Hesp) is a common flavanone glycoside compound that has been demonstrated to exhibit a variety of biological and pharmacological properties that include anti-inflammatory and antioxidant properties. The aim of this study is to explore the ability of Hesp to attenuate oxidative damage in hydrogen peroxide (H2O2)-stimulated ARPE-19 cells. The results indicated that Hesp treatment not only increased cell survival but also decreased reactive oxygen species (ROS) generation, whereas these roles were effectively enhanced the superoxide dismutase (SOD) and glutathione (GSH) levels, and reduced malondialdehyde (MDA) formation. Importantly, the level of heme oxygenase-1 (HO-1) expression was increased by Hesp exposure, which resulted in a decrease after the transfection of cells with Nrf2-siRNA. Additionally, further results revealed that Hesp treatment significantly elevated Keap-1 protein expression, Nrf2 nuclear translocation and ARE activities. These observations indicated that Hesp treatment effectively protected against H2O2-induced oxidative damage in ARPE-19 cells by inhibiting cell apoptosis, ROS overproduction and MDA formation as well as enhancing the SOD and GSH levels. The underlying mechanisms may be related to the activation of the Keap1-Nrf2/HO-1 signal pathway, which may provide biological evidence to further encourage the investigation of the protective effect of Hesp in AMD disease.
authors.affiliation: Department of Ophthalmology, Second Hospital of Jilin University, Changchun 130041, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology, Second Hospital of Jilin University, Changchun 130041, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Ophthalmology, First Hospital of Jilin University, Changchun 130021, China, China.
authors.forename: Haile
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, First Hospital of Jilin University, Changchun 130021, China, China. Electronic address: lvhm63251@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Ophthalmology, First Hospital of Jilin University, Changchun 130021, China, China. Electronic address: cz3531@163.com.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Cui
mesh_terms: D061745:Antioxidant Response Elements / Q000235:genetics; D000975:Antioxidants / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D034741:RNA, Small Interfering; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D006569:Hesperidin; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D005978:Glutathione; C013015:hesperetin
keywords: AMD; HO-1; Hesperetin; Nrf2; Oxidative stress