Several experiments have been performed with the objective to identify substances that can activate Nrf-2 and enhance the expression of Nrf-2 target genes in human RPE cells (ARPE-19 cells). The lutein treatment significantly increased the transcription of NQO1 by 1.7 0.1-fold, glutamate-cysteine ligase regulatory subunit (GCLm) by 1.4 0.1-fold, and HO-1 by 1.8 0.3-fold, leading to an enhanced resistance of RPE cells against oxidative damage(106)106 Frede K, Ebert F, Kipp AP, Schwerdtle T, Baldermann S. Lutein activates the transcription factor nrf2 in human retinal pigment epithelial cells. J Agric Food Chem. 2017;65(29):5944-52.. Other carotenoids can also activate Nrf-2 in the RPE. Astaxanthin led to an increase (2.3-fold) of nuclear Nrf-2 after incubation of ARPE-19 cells with astaxanthin. This carotenoid also induced transcription levels of NQO1 by 1.3-fold of GCLm by 1.9-fold, and of HO-1 by 2-fold(107)107 Li Z, Dong X, Liu H, Chen X, Shi H, Fan Y, et al. Astaxanthin protects ARPE-19 cells from oxidative stress via upregulation of Nrf2-regulated phase II enzymes through activation of PI3K/Akt. Mol Vis. 2013;19:1656-66.. Cells treated with astaxanthin and then exposed to blue light light-emitting diode upregulated the Nrf-2-ARE pathway and facilitated the expression of phase II antioxidant enzymes, HO-1 and NQO-1(108)108 Lin CW, Yang CM, Yang CH. Protective effect of astaxanthin on blue light light-emitting diode-induced retinal cell damage via free radical scavenging and activation of PI3K/Akt/Nrf-2 pathway in 661W cell model. Mar Drugs. 2020;18(8):387.. Zeaxanthin was also observed to increase nuclear Nrf-2 in ARPE-19 cells and upregulated Nrf-2 target genes even more strongly. The transcription levels of NQO1 increased by 3.7-fold, of GCLm by 3.2-fold, and of HO-1 by 4.5-fold. The same study also showed that zeaxanthin induces Nrf-2 target genes and GSH levels in rats and reduces the oxidative damage in the retina of these animals(109)109 Zou X, Gao J, Zheng Y, Wang X, Chen C, Cao K, et al. Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. Cell Death Dis. 2014;5(5):e1218.. Escin, a natural triterpene-saponin, was reported to increase nuclear Nrf-2 levels and induce NQO1 mRNA by 9-fold and HO-1 mRNA by 17-fold after incubation of ARPE-19 cells with 10 μM of escin for 2 hours. Thus, escin is a stronger inducer than lutein(110)110 Wang K, Jiang Y, Wang W, Ma J, Chen M. Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress. Biochem Biophys Res Commun. 2015;468(4):541-7.. Furthermore, different phenolic compounds enhance Nrf-2 target genes in the RPE. For example, treatment of ARPE-19 cells with 50 μM of canolol for 24 hours led to a 1.5-fold induction of HO-1 mRNA(111)111 Dong X, Li Z, Wang W, Zhang W, Liu S, Zhang X, et al. Protective effect of canolol from oxidative stress-induced cell damage in ARPE-19 cells via an ERK mediated antioxidative pathway. Mol Vis. 2011;17:2040-8.. Eriodictyol, a flavonoid found in citrus fruits, induced the nuclear translocation of Nrf-2 and increased HO-1 protein levels, NQO1 protein levels, and glutathione after incubating ARPE-19 cells with eriodictyol at a concentration of 0-100 μM for 2-24 hours(112)112 Johnson J, Maher P, Hanneken A. The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through its effects on Nrf2 activation and phase 2 gene expression. Invest Ophthalmol Vis Sci. 2009;50(5):2398-406.. Glycyrrhizin, a bioactive triterpenoid saponin extracted from a traditional Chinese medicinal herb, glycyrrhiza, increased expression of Nrf-2 and HO-1, playing a protective role in RPE(113)113 He H, Wei D, Liu H, Zhu C, Lu Y, Ke Z, et al. Glycyrrhizin protects against sodium iodate-induced RPE and retinal injury though activation of AKT and Nrf2/HO-1 pathway. J Cell Mol Med. 2019;23(5):3495-504.. Hispidin, a polyphenol compound isolated from Phellinus linteus, markedly enhanced the expression of Nrf-2, HO-1, NQO-1, glutamate-cysteine ligase catalytic subunit, and GCLM in a dose-dependent manner(114)114 Huang SY, Chang SF, Chau SF, Chiu SC. The protective effect of hispidin against hydrogen peroxide-induced oxidative stress in ARPE-19 Cells via Nrf-2 signaling pathway. Biomolecules. 2019;9(8):380.. Curcumin induced expression of the HO-1 and protected cells against oxidative stress in cultured human RPE cells(9999 Mandal MN, Patlolla JM, Zheng L, Agbaga MP, Tran JT, Wicker L, et al. Curcumin protects retinal cells from light-and oxidant stress-induced cell death. Free Radic Biol Med. 2009;46(5):672-9.,115115 Woo JM, Shin DY, Lee SJ, Joe Y, Zheng M, Yim JH, et al. Curcumin protects retinal pigment epithelial cells against oxidative stress via induction of heme oxygenase-1 expression and reduction of reactive oxygen. Mol Vis. 2012;18:901-8.).
Fruit Hoop Activation Code [Ativador]l
2ff7e9595c
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