Salidroside prevents hydroperoxide‑induced oxidative stress and apoptosis in retinal pigment epithelium cells

Yin,Yan; Liu,Dejie; Tian,Donghua

doi:10.3892/etm.2018.6494

Salidroside prevents hydroperoxide‑induced oxidative stress and apoptosis in retinal pigment epithelium cells

Authors:
- Yan Yin
- Dejie Liu
- Donghua Tian
View Affiliations

Affiliations: Department of Ophthalmology, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China, Department of Ophthalmology, Yantai Yeda Hospital, Yantai, Shandong 264006, P.R. China
Published online on: July 20, 2018 https://doi.org/10.3892/etm.2018.6494
Pages: 2363-2368
Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Salidroside (SAL) is the major pharmacologically active constituent of Rhodiola rosea, which possesses a wide range of pharmacological functions, including anti‑aging, anti‑inflammatory, antioxidant, anticancer and neuroprotective activities. However, the effects and mechanisms of SAL on oxidative stress in retinal pigment epithelial (RPE) cells exposed to hydrogen peroxide (H2O2) remain unclear. The present study investigated the protective effects of SAL and the underlying mechanisms against H2O2‑induced oxidative stress in human RPE cells. ARPE‑19 cells were treated with various doses of SAL for 24 h and then exposed to 200 µM H2O2 for 24 h. Cell viability was analyzed by a MTT assay, and the intracellular levels of reactive oxygen species were measured using CellROX orange reagent. Cell apoptosis was analyzed by annexin V/propidium iodide double staining, followed by flow cytometry. The levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein, phospho (p)‑protein kinase B (Akt), Akt, p‑glycogen synthase kinase (GSK)‑3β and GSK‑3β were evaluated using western blotting. The results demonstrated that SAL markedly attenuated H2O2‑induced loss of cell viability. SAL also ameliorated H2O2‑induced oxidative stress and cell apoptosis in RPE cells. In addition, pretreatment with SAL significantly increased the phosphorylation levels of Akt and GSK‑3β in H2O2‑treated ARPE‑19 cells. In conclusion, the present study demonstrated that SAL protected RPE cells against H2O2‑induced cell injury through the activation of the Akt/GSK‑3β signaling pathway. This suggests that SAL may be a potential therapeutic strategy for the treatment of age‑related macular degeneration.

View Figures

View References

1	Friedman DS, O'Colmain BJ, Muñoz B, Tomany SC, Mccarty C, de Jong PT, Nemesure B, Nemesure B, Mitchell P and Kempen J; Eye Diseases Prevalence Research Group, : Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 122:564–572. 2004. View Article : Google Scholar : PubMed/NCBI
2	Strauss O: The retinal pigment epithelium in visual function. Physiol Rev. 85:845–881. 2005. View Article : Google Scholar : PubMed/NCBI
3	Dong A, Xie B, Shen J, Yoshida T, Yokoi K, Hackett SF and Campochiaro PA: Oxidative stress promotes ocular neovascularization. J Cell Physiol. 219:544–552. 2009. View Article : Google Scholar : PubMed/NCBI
4	Lu L, Hackett SF, Mincey A, Lai H and Campochiaro PA: Effects of different types of oxidative stress in RPE cells. J Cell Physiol. 206:119–125. 2006. View Article : Google Scholar : PubMed/NCBI
5	Glotin AL, Calipel A, Brossas JY, Faussat AM, Tréton J and Mascarelli F: Sustained versus transient ERK1/2 signaling underlies the anti- and proapoptotic effects of oxidative stress in human RPE cells. Invest Ophthalmol Vis Sci. 47:4614–4623. 2006. View Article : Google Scholar : PubMed/NCBI
6	Beatty S, Koh H, Phil M, Henson D and Boulton M: The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 45:115–134. 2000. View Article : Google Scholar : PubMed/NCBI
7	Sun L, Isaak CK, Zhou Y, Petkau JC, O K, Liu Y and Siow YL: Salidroside and tyrosol from Rhodiola protect H9c2 cells from ischemia/reperfusion-induced apoptosis. Life Sci. 91:151–158. 2012. View Article : Google Scholar : PubMed/NCBI
8	Li D, Fu Y, Zhang W, Su G, Liu B, Guo M, Li F, Liang D, Liu Z, Zhang X, et al: Salidroside attenuates inflammatory responses by suppressing nuclear factor-κB and mitogen activated protein kinases activation in lipopolysaccharide-induced mastitis in mice. Inflamm Res. 62:9–15. 2013. View Article : Google Scholar : PubMed/NCBI
9	Mao GX, Wang Y, Qiu Q, Deng HB, Yuan LG, Li RG, Song DQ, Li YY, Li DD and Wang Z: Salidroside protects human fibroblast cells from premature senescence induced by H(2)O(2) partly through modulating oxidative status. Mech Ageing Dev. 131:723–731. 2010. View Article : Google Scholar : PubMed/NCBI
10	Hu X, Zhang X, Qiu S, Yu D and Lin S: Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells. Biochem Bioph Res Commun. 398:62–67. 2010. View Article : Google Scholar
11	Shi TY, Feng SF, Xing JH, Wu YM, Li XQ, Zhang N, Tian Z, Liu SB and Zhao MG: Neuroprotective effects of Salidroside and its analogue tyrosol galactoside against focal cerebral ischemia in vivo and H2O2-induced neurotoxicity in vitro. Neurotox Res. 21:358–367. 2012. View Article : Google Scholar : PubMed/NCBI
12	Zhang L, Yu H, Zhao X, Lin X, Tan C, Cao G and Wang Z: Neuroprotective effects of salidroside against beta-amyloid-induced oxidative stress in SH-SY5Y human neuroblastoma cells. Neurochem Int. 57:547–555. 2010. View Article : Google Scholar : PubMed/NCBI
13	Baek SM, Yu SY, Son Y and Hong HS: Substance P promotes the recovery of oxidative stress-damaged retinal pigmented epithelial cells by modulating Akt/GSK-3β signaling. Mol Vis. 22:1015–1023. 2016.PubMed/NCBI
14	Cao X, Liu M, Tuo J, Shen D and Chan CC: The effects of quercetin in cultured human RPE cells under oxidative stress and in Ccl2/Cx3cr1 double deficient mice. Exp Eye Res. 91:15–25. 2010. View Article : Google Scholar : PubMed/NCBI
15	Cia D, Vergnaud-Gauduchon J, Jacquemot N and Doly M: Epigallocatechin gallate (EGCG) prevents H2O2-induced oxidative stress in primary rat retinal pigment epithelial cells. Curr Eye Res. 39:944–952. 2014. View Article : Google Scholar : PubMed/NCBI
16	Koskela A, Reinisalo M, Hyttinen JM, Kaarniranta K and Karjalainen RO: Pinosylvin-mediated protection against oxidative stress in human retinal pigment epithelial cells. Mol Vis. 20:760–769. 2014.PubMed/NCBI
17	Liang FQ and Godley BF: Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: A possible mechanism for RPE aging and age-related macular degeneration. Exp Eye Res. 76:397–403. 2003. View Article : Google Scholar : PubMed/NCBI
18	Beatty S, Koh H, Phil M, Henson D and Boulton M: The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 45:115–134. 2000. View Article : Google Scholar : PubMed/NCBI
19	Klein R, Myers CE, Cruickshanks KJ, Gangnon RE, Danforth LG, Sivakumaran TA, Iyengar SK, Tsai MY and Klein BE: Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: The beaver dam eye study. JAMA Ophthalmol. 132:446–455. 2014. View Article : Google Scholar : PubMed/NCBI
20	Xu MC, Shi HM, Wang H and Gao XF: Salidroside protects against hydrogen peroxide-induced injury in HUVECs via the regulation of REDD1 and mTOR activation. Mol Med Rep. 8:147–153. 2013. View Article : Google Scholar : PubMed/NCBI
21	Zhu Y, Shi YP, Wu D, Ji YJ, Wang X, Chen HL, Wu SS, Huang DJ and Jiang W: Salidroside protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via PI3K-Akt dependent pathway. Dna Cell Biol. 30:809–819. 2011. View Article : Google Scholar : PubMed/NCBI
22	Fujihara M, Nagai N, Sussan TE, Biswal S and Handa JT: Chronic cigarette smoke causes oxidative damage and apoptosis to retinal pigmented epithelial cells in mice. PLoS One. 3:e31192008. View Article : Google Scholar : PubMed/NCBI
23	Mao H, Seo SJ, Biswal MR, Li H, Conners M, Nandyala A, Jones K, Le YZ and Lewin AS: Mitochondrial oxidative stress in the retinal pigment epithelium leads to localized retinal degeneration. Invest Ophthalmol Vis Sci. 55:4613–4627. 2014. View Article : Google Scholar : PubMed/NCBI
24	Shi K, Wang X, Zhu J, Cao G, Zhang K and Su Z: Salidroside protects retinal endothelial cells against hydrogen peroxide-induced injury via modulating oxidative status and apoptosis. Biosci Biotechnol Biochem. 79:1406–1413. 2015. View Article : Google Scholar : PubMed/NCBI
25	Qiao Z, Xu YW and Yang J: Eupatilin inhibits the apoptosis in H9c2 cardiomyocytes via the Akt/GSK-3β pathway following hypoxia/reoxygenation injury. Biomed Pharmacother. 82:373–378. 2016. View Article : Google Scholar : PubMed/NCBI
26	Lv D, Bai Z, Yang L, Li X and Chen X: Lipid emulsion reverses bupivacaine-induced apoptosis of h9c2 cardiomyocytes: PI3K/Akt/GSK-3β signaling pathway. Environ Toxicol Pharmacol. 42:85–91. 2016. View Article : Google Scholar : PubMed/NCBI
27	Ramírez-Sánchez J, Simões Pires EN, Nuñez-Figueredo Y, Pardo-Andreu GL, Fonseca-Fonseca LA, Ruiz-Reyes A, Ochoa-Rodríguez E, Verdecia-Reyes Y, Delgado-Hernández R, Souza DO and Salbego C: Neuroprotection by JM-20 against oxygen-glucose deprivation in rat hippocampal slices: Involvement of the Akt/GSK-3β pathway. Neurochem Int. 90:215–223. 2015. View Article : Google Scholar : PubMed/NCBI
28	Yang P, Peairs JJ, Tano R and Jaffe GJ: Oxidant-mediated Akt activation in human RPE cells. Invest Ophthalmol Vis Sci. 47:4598–4606. 2006. View Article : Google Scholar : PubMed/NCBI
29	Yan T, Bi H and Wang Y: Wogonin modulates hydroperoxide-induced apoptosis via PI3K/Akt pathway in retinal pigment epithelium cells. Diagn Pathol. 9:1542014. View Article : Google Scholar : PubMed/NCBI
30	Wang K, Jiang Y, Wang W, Ma J and Chen M: Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress. Biochem Bioph Res Commun. 468:541–547. 2015. View Article : Google Scholar