Browse > Article
http://dx.doi.org/10.5352/JLS.2019.29.11.1273

Ethanol Extract of Glycyrrhiza uralensis Protects Against Oxidative Stress-induced DNA Damage and Apoptosis in Retinal Pigment Epithelial Cells  

Kim, So Young (Department of Biochemistry, Dong-eui University College of Korean Medicine)
Kim, Jeong-Hwan (Research and Development Department, BGN CARE Co., Ltd.)
Kim, Sung Ok (Department of Food Science and Biotechnology, College of Engineering, Kyungsung University)
Park, Seh-Kwang (Research and Development Department, BGN CARE Co., Ltd.)
Jeong, Ji-Won (BGN Eye Clinic)
Kim, Mi-Young (Research and Development Department, BGN CARE Co., Ltd.)
Lee, Hyesook (Department of Biochemistry, Dong-eui University College of Korean Medicine)
Cheong, JaeHun (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Choi, Yung Hyun (Department of Biochemistry, Dong-eui University College of Korean Medicine)
Publication Information
Journal of Life Science / v.29, no.11, 2019 , pp. 1273-1280 More about this Journal
Abstract
Age-related macular degeneration (AMD) is one of the leading causes of blindness in the elderly population, and damage to retinal pigment epithelial (RPE) cells due to oxidative stress contributes to the development of AMD. Glycyrrhiza uralensis Fischer is one of the most widely used herbal medicines for the treatment of various diseases in Asian countries. Although recent studies indicated that treatment with G. uralensis can protect cells from oxidative stress, its mechanisms in RPE cells remain unknown. We evaluated the effect of a G. uralensis ethanol extract (GU) on $H_2O_2$-induced oxidative injury in ARPE-19 RPE cells. The GU pretreatment attenuated reactive oxygen species (ROS) generation induced by $H_2O_2$, which was associated with induced expression of nuclear factor erythroid-derived-2-like 2 (Nrf2) and heme oxygenase-1 (HO-1). GU also suppressed $H_2O_2$-induced DNA damage and mitochondrial dysfunction. The inhibitory effect of GU on $H_2O_2$-induced apoptosis was associated with the protection of caspase-3 activation. Overall, GU appeared to protect RPE cells from oxidative injury by inhibiting DNA damage and reducing apoptosis. Further studies are needed to determine the regulation of Nrf2-mediated HO-1 expression, but our results suggest the possibility of using GU to reduce the risk of AMD.
Keywords
Apoptosis; DNA damage; Nrf2/HO-1; oxidative stress; retinal pigment epithelial cells;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Deng, Y., Zhu, J., Mi, C., Xu, B., Jiao, C., Li, Y., Xu, D., Liu, W. and Xu, Z. 2015. Melatonin antagonizes Mn-induced oxidative injury through the activation of keap1-Nrf2-ARE signaling pathway in the striatum of mice. Neurotox. Res. 27, 156-171.   DOI
2 Dunaief, J. L., Dentchev, T., Ying, G. S. and Milam, A. H. 2002. The role of apoptosis in age-related macular degeneration. Arch. Ophthalmol. 120, 1435-1442.   DOI
3 Geric, M., Gajski, G. and Garaj-Vrhovac, V. 2014. $\gamma$-H2AX as a biomarker for DNA double-strand breaks in ecotoxicology. Ecotoxicol. Environ. Saf. 105, 13-21.   DOI
4 Gong, H., Zhang, B. K., Yan, M., Fang, P. F., Li, H. D., Hu, C. P., Yang, Y., Cao, P., Jiang, P. and Fan, X. R. 2015. A protective mechanism of licorice (Glycyrrhiza uralensis): isoliquiritigenin stimulates detoxification system via Nrf2 activation. J. Ethnopharmacol. 162, 134-139.   DOI
5 Hao, Y., Liu, J., Wang, Z., Yu, L. L. and Wang, J. 2019. Piceatannol protects human retinal pigment epithelial cells against hydrogen peroxide induced oxidative stress and apoptosis through modulating PI3K/Akt signaling pathway. Nutrients 11, E1515.   DOI
6 Liu, D., Huo, X., Gao, L., Zhang, J., Ni, H. and Cao, L. 2018. $NF-{\kappa}B$ and Nrf2 pathways contribute to the protective effect of licochalcone A on dextran sulphate sodium-induced ulcerative colitis in mice. Biomed. Pharmacother. 102, 922-929.   DOI
7 Liu, Y., Ren, Y., Wang, X., Liu, X., Xu, Y. and He, Y. 2019. Down regulation of UCP2 expression in retinal pigment epithelium cells under oxidative stress: an in vitro study. Int. J. Ophthalmol. 12, 1089-1094.
8 Marazita, M. C., Dugour, A., Marquioni-Ramella, M. D., Figueroa, J. M. and Suburo, A. M. 2016. Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: Implications for age-related macular degeneration. Redox. Biol. 7, 78-87.   DOI
9 Hoffman, D. L. and Brookes, P. S. 2009. Oxygen sensitivity of mitochondrial reactive oxygen species generation depends on metabolic conditions. J. Biol. Chem. 284, 16236-16245.   DOI
10 He Y., Leung K. W., Ren Y., Pei J., Ge, J. and Tombran-Tink, J. 2014. PEDF improves mitochondrial function in RPE cells during oxidative stress. Invest. Ophthalmol. Vis. Sci. 55, 6742-6755.   DOI
11 Hsieh, F. C., Hung, C. T., Cheng, K. C., Wu, C. Y., Chen, Y. C., Wu, Y. J., Liu, W. and Chiu, C. C. 2018. Protective effects of Lycium barbarum extracts on UVB-induced damage in human retinal pigment epithelial cells accompanied by attenuating ROS and DNA damage. Oxid. Med. Cell. Longev. 2018, 4814928.   DOI
12 Kaspar, J. W., Niture, S. K. and Jaiswal, A. K. 2009. Nrf2: INrf2 (Keap1) signaling in oxidative stress. Free Radic. Biol. Med. 47, 1304-1309.   DOI
13 Hyttinen, J. M. T., Viiri, J., Kaarniranta, K. and Blasiak, J. 2018. Mitochondrial quality control in AMD: does mitophagy play a pivotal role? Cell. Mol. Life Sci. 75, 2991-3008.   DOI
14 Ji, S., Li, Z., Song, W., Wang, Y., Liang, W., Li, K., Tang, S., Wang, Q., Qiao, X., Zhou, D., Yu, S. and Ye, M. 2016. Bioactive constituents of Glycyrrhiza uralensis (Licorice): Discovery of the effective components of a traditional herbal medicine. J. Nat. Prod. 79, 281-292.   DOI
15 Kao, T. C., Wu, C. H. and Yen, G. C. 2014. Bioactivity and potential health benefits of licorice. J. Agric. Food Chem. 62, 542-553.   DOI
16 van Lookeren Campagne, M., LeCouter, J., Yaspan, B. L. and Ye, W. 2014. Mechanisms of age-related macular degeneration and therapeutic opportunities. Pathology 232, 151-164.   DOI
17 Ni, T., Yang, W. and Xing, Y. 2019. Protective effects of delphinidin against $H_2O_2$-induced oxidative injuries in human retinal pigment epithelial cells. Biosci. Rep. 39, BSR20190689.
18 Park, C., Lee, H., Hong, S. H., Kim, J. H., Park, S. K., Jeong, J. W., Kim, G. Y., Hyun, J. W., Yun, S. J., Kim, B. W., Kim, W. J. and Choi, Y. H. 2019. Protective effect of diphlorethohydroxycarmalol against oxidative stress-induced DNA damage and apoptosis in retinal pigment epithelial cells. Cutan. Ocul. Toxicol. 38, 298-308.   DOI
19 Rotstein, N. P, Miranda, G. E, Abrahan, C. E. and German, O. L. 2010. Regulating survival and development in the retina: key roles for simple sphingolipids. J. Lipid Res. 51, 1247-1262.   DOI
20 Wang, K., Jiang, Y., Wang, W., Ma, J. and Chen, M. 2015. Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress. Biochem. Biophys. Res. Commun. 468, 541-547.   DOI
21 Li, Z., Dong, X., Liu, H., Chen, X., Shi, H., Fan, Y., Hou, D. and Zhang, X. 2013. Astaxanthin protects ARPE-19 cells from oxidative stress via upregulation of Nrf2-regulated phase II enzymes through activation of PI3K/Akt. Mol. Vis. 19, 1656-1666.
22 Leveillard, T. and Klipfel, L. 2019. Mechanisms underlying the visual benefit of cell transplantation for the treatment of retinal degenerations. Int. J. Mol. Sci. 20, E557.   DOI
23 Li, K. R., Yang, S. Q., Gong, Y. Q., Yang, H., Li, X. M., Zhao, Y. X., Yao, J., Jiang, Q. and Cao, C. 2016. 3H-1,2-dithiole-3-thione protects retinal pigment epithelium cells against Ultra-violet radiation via activation of Akt-mTORC1-dependent Nrf2-HO-1 signaling. Sci. Rep. 6, 25525.   DOI
24 Li, X. M., Huang, D., Yu, Q., Yang, J. and Yao, J. 2018. Neuroligin-3 protects retinal cells from $H_2O_2$-induced cell death via activation of Nrf2 signaling. Biochem. Biophys. Res. Commun. 502, 166-172.   DOI
25 Zhu, C., Dong, Y., Liu, H., Ren, H. and Cui, Z. 2017. Hesperetin protects against $H_2O_2$-triggered oxidative damage via upregulation of the Keap1-Nrf2/HO-1 signal pathway in ARPE-19 cells. Biomed. Pharmacother. 88, 124-133.   DOI
26 Wang, Z., Hao, Y., Wang, Y., Liu, J., Yuan, X., Sun, B. and Wang, J. 2019. Wheat alkylresorcinols protect human retinal pigment epithelial cells against $H_2O_2$-induced oxidative damage through Akt-dependent Nrf2/HO-1 signaling. Food Funct. 10, 2797-2804.   DOI
27 Yan, G., Yu, L., Jiang, S. and Zhu, J. 2018. Melatonin antagonizes oxidative stress-induced mitochondrial dysfunction in retinal pigmented epithelium cells via melatonin receptor 1 (MT1). J. Toxicol. Sci. 43, 659-669.   DOI
28 Yang, P. M., Wu, Z. Z., Zhang, Y. Q. and Wung, B. S. 2016. Lycopene inhibits ICAM-1 expression and $NF-{\kappa}B$ activation by Nrf2-regulated cell redox state in human retinal pigment epithelial cells. Life Sci. 155, 94-101.   DOI
29 Zhang, D. D. 2006. Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab. Rev. 38, 769-789.   DOI
30 Zhao, Z., Chen, Y., Wang, J., Sternberg, P., Freeman, M. L., Grossniklaus, H. E. and Cai, J. 2011. Age-related retinopathy in NRF2-deficient mice. PLoS One 6, e19456.   DOI
31 Caito, S. W. and Aschner, M. 2015. Mitochondrial redox dysfunction and environmental exposures. Antioxid. Redox. Signal. 23, 578-595.   DOI
32 Arumugam, B., Palanisamy, U. D., Chua, K. H. and Kuppusamy, U. R. 2019. Protective effect of myricetin derivatives from Syzygium malaccense against hydrogen peroxide-induced stress in ARPE-19 cells. Mol. Vis. 25, 47-59.
33 Bao, F., Bai, H. Y., Wu, Z. R. and Yang, Z. G. 2019. Phenolic compounds from cultivated Glycyrrhiza uralensis and their PD-1/PD-L1 inhibitory activities. Nat. Prod. Res. 25, 1-8.   DOI
34 Brown, E. E., Lewin, A. S. and Ash, J. D. 2018. Mitochondria: Potential targets for protection in age-related macular degeneration. Adv. Exp. Med. Biol. 1074, 11-17.   DOI
35 Demine, S., Renard, P. and Arnould, T. 2019. Mitochondrial uncoupling: A key controller of biological processes in physiology and diseases. Cells 8, E795.   DOI
36 Cao, L. J., Hou, Z. Y., Li, H. D., Zhang, B. K., Fang, P. F., Xiang, D. X., Li, Z. H., Gong, H., Deng, Y., Ma, Y. X., Tang, H. B. and Yan, M. 2017. The ethanol extract of Licorice (Glycyrrhiza uralensis) protects against triptolide-induced oxidative stress through activation of Nrf2. Evid. Based Complement. Alternat. Med. 2017, 2752389.