Mogroside regulates the oxidative stress response of retinal pigment epithelial cells induced by H<sub>2</sub>O<sub>2</sub> through silent information regulator of transcription 1/nuclear factor erythroid-2-related actor 2 signaling pathway_Chinese Journal of Ocular Fundus Diseases

Authors：

Niu Chao , Cui Longjiang , Dong Daoquan ,  Li Xiaohua

Eye Laser Room, Henan Provincial Eye Hospital, Zhengzhou 450003, China;

Corresponding author：

Li Xiaohua, Email: superbull000@163.com

Keywords：

Mogroside; Retinal pigment epithelial cells; Oxidative stress; Reactive oxygen species; Silent information regulator of transcription 1; Nuclear factor erythroid-2-related actor 2; Cell experiment

DOI：

10.3760/cma.j.cn511434-20211102-00625

Video：

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Objective To observe and preliminarily explore the effect of mogroside on oxidative stress of retinal pigment epitheliaum (RPE) cells induced by hydrogen peroxide (H₂O₂) and its possible mechanism. Methods A experimental study. The RPE cells were divided into control group, H₂O₂ group, silent information regulator of transcription 1 (SIRT1) inhibitor EX527 group (EX527 group), mogroside group, mogroside+EX527 group. Methyl thiazolete trazolium method was used to detect cell survival rate. Flow cytometry was used to detect cell apoptosis rate. 2',7'-dichlorodihydrofluorescein diacetate fluorescent probe method, xanthine method and enzyme-linked immunosorbent assay method were used to detect the level of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in cells respectively. Real-time quantitative polymerase chain reaction and Western blot were used to detect relative expressions of SIRT1, nuclear factor erythroid-2-related actor 2 (Nrf2), heme oxygenase-1 (HO-1) mRNA and protein in cells. One-way ANOVA was used for comparison among groups. The pairwise comparison between groups was tested by the least significant difference t test. Results Compared with the control group, the H₂O₂ group cell survival rate decreased, the apoptosis rate increased, the ROS level in the cells increased, the SOD activity decreased, the MDA content increased, and the relative expression of SIRT1, Nrf2, HO-1 mRNA and protein decreased (P＜0.05). Compared with H₂O₂ group, the cell survival rate decreased, apoptosis rate increased, the cell ROS level increased, SOD activity decreased, MDA content increased, SIRT1, Nrf2, HO-1 mRNA and protein expression decreased in EX527 group (P＜0.05); the cell survival rate increased, apoptosis rate decreased, ROS level decreased, SOD activity increased, MDA content decreased, and the relative expression of SIRT1, Nrf2, HO-1 mRNA and protein increased in mogroside group (P＜0.05). Compared with the mogrosides group, the cell survival rate decreased, the apoptosis rate increased, the level of ROS increased, SOD activity decreased, MDA content increased, SIRT1, Nrf2, HO-1 mRNA and protein decreased in mogrosides+EX527 group (P＜0.05). Conclusions Mogrosides can alleviate the oxidative stress response of visual RPE cells induced by H₂O₂, promote cell proliferation, and reduce cell apoptosis. Mogrosides may exert antioxidant effects by activating the SIRT1/Nrf2 signaling pathway.

Citation： Niu Chao, Cui Longjiang, Dong Daoquan, Li Xiaohua. Mogroside regulates the oxidative stress response of retinal pigment epithelial cells induced by H₂O₂ through silent information regulator of transcription 1/nuclear factor erythroid-2-related actor 2 signaling pathway. Chinese Journal of Ocular Fundus Diseases, 2023, 39(7): 576-582. doi: 10.3760/cma.j.cn511434-20211102-00625 Copy

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4.	Srinivasan M, Ravindran RD, O'Brien KS, et alAntioxidant vitamins for cataracts: 15-year follow-up of a randomized trial[J]. Ophthalmology20201277986987. DOI:10.1016/j.ophtha.2020.01.050.
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6.	于万芹, 杜晓娜, 刘巧敏, 等罗汉果皂苷对妊娠糖尿病大鼠氧化应激损伤影响[J]. 中国临床药理学杂志2019352127232727. DOI:10.13699/j.cnki.1001-6821.2019.21.021..Yu WQ, Du XN, Liu QM, et alEffects of Momordica grosvenori saponin on oxidative stress injury in gestational diabetic rats[J]. Chin J Clin Pharmacol2019352127232727. DOI:10.13699/j.cnki.1001-6821.2019.21.021.
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10.	张惟, 杨婧, 陈松, 等氧化应激下视网膜色素上皮细胞外泌体对视网膜色素上皮细胞血管内皮生长因子A及丝氨酸/苏氨酸激酶表达的影响[J]. 中华眼底病杂志20173315761. DOI:10.3760/cma.j.issn.1005-1015.2017.01.015..Zhang W, Yang J, Chen S, et alInfluence of oxidative stress-induced exosomes on Akt and vascular endothelial growth faetor-A of retinal pigment epithelium cells[J]. Chin J Ocul Fundus Dis20173315761. DOI:10.3760/cma.j.issn.1005-1015.2017.01.015.
11.	Li X, Wang Q, Ren Y, et alTetramethylpyrazine protects retinal ganglion cells against H2O2-induced damage via the microRNA-182/mitochondrial pathway[J]. Int J Mol Med2019442503512. DOI: 10.3892/ijmm.2019.4214. doi:10.3892/ijmm.2019.4214.
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13.	Hwang N, Kwon MY, Woo JM, et alOxidative stress-induced pentraxin 3 expression human retinal pigment epithelial cells is involved in the pathogenesis of age-related macular degeneration[J]. Int J Mol Sci201920236028. DOI: 10.3390/ijms20236028.
14.	Balan DJ, Rajavel T, Das M, et alThymol induces mitochondrial pathway-mediated apoptosis via ROS generation, macromolecular damage and SOD diminution in A549 cells[J]. Pharmacol Rep2021731240254. DOI: 10.1007/s43440-020-00171-6.
15.	Ekin S, Yildiz H, Alp HHNOX4, MDA, IMA and oxidative DNA damage: can these parameters be used to estimate the presence and severity of OSA?[J]. Sleep Breath2021251529536. DOI: 10.1007/s11325-020-02093-2.
16.	Xiao R, Liao W, Luo G, et alModulation of gut microbiota composition and short-chain fatty acid synthesis by mogroside V in an in vitro incubation system[J]. ACS Omega20216392548625496. DOI: 10.1021/acsomega.1c03485.
17.	黄文蔚, 洪李锋, 郭璠, 等罗汉果皂苷对阿霉素心肌损伤大鼠氧化应激和凋亡调节作用研究[J]. 辽宁中医药大学学报20192163942. DOI: 10.13194/j.issn.1673-842x.2019.06.010..Huang WW, Hong LF, Guo P, et alEffect of mogmside on oxidative stress and cell apoptosis in myocardium of adriamycin myocardial injury rat[J]. J Liaoning Univ Tradit Chine Med20192163942. DOI: 10.13194/j.issn.1673-842x.2019.06.010.
18.	Li Y, Zou L, Li T, et alMogroside V inhibits LPS-induced COX-2 expression/ROS production and overexpression of HO-1 by blocking phosphorylation of AKT1 in RAW264.7 cells[J]. Acta Biochim Biophys Sin (Shanghai)2019514365374. DOI:10.1093/abbs/gmz014.
19.	Luo Y, Lu S, Gao Y, et alAraloside C attenuates atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy[J]. Aging (Albany NY)202012217041724. DOI: 10.18632/aging.102708.
20.	Abozaid OAR, Sallam MW, El-Sonbaty S, et alResveratrol-selenium nanoparticles alleviate neuroinflammation and neurotoxicity in a rat model of Alzheimer's disease by regulating sirt1/miRNA-134/GSK3β expression[J]. Biol Trace Elem Res20222001251045114. DOI: 10.1007/s12011-021-03073-7.
21.	Wang H, Su X, Zhang QQ, et alMicroRNA-93-5p participates in type 2 diabetic retinopathy through targeting Sirt1[J]. Int Ophthalmol2021411138373848. DOI: 10.1007/s10792-021-01953-4.
22.	Xiu C, Jiang J, Song RExpression of miR-34a in cataract rats and its related mechanism[J]. Exp Ther Med202019210511057. DOI: 10.3892/etm.2019.8295.
23.	Patruno A, Costantini E, Ferrone A, et alShort ELF-EMF exposure targets SIRT1/Nrf2/HO-1 signaling in THP-1 cells[J]. Int J Mol Sci202021197284. DOI: 10.3390/ijms21197284.
24.	Wang G, Xie X, Yuan L, et alResveratrol ameliorates rheumatoid arthritis via activation of SIRT1-Nrf2 signaling pathway[J]. Biofactors2020463441453. DOI: 10.1002/biof.1599.
25.	Samimi F, Baazm M, Eftekhar E, et alPossible antioxidant mechanism of coenzyme Q10 in diabetes: impact on Sirt1/Nrf2 signaling pathways[J]. Res Pharm Sci2019146524533. doi:10.4103/1735-5362.272561.

1. McGuinness MB, Karahalios A, Finger RP, et alAge-related macular degeneration and mortality: a systematic review and meta-analysis[J]. Ophthalmic Epidemiol2017243141152. DOI: 10.1080/09286586.2016.1259422.
2. 庄宏, 张荣, 舒秦蒙, 等人脐带间充质干细胞对光诱导视网膜色素上皮细胞损伤的保护作用[J]. 中华实验眼科杂志20193711863869. DOI:10.3760/cma.j.issn.2095-0160.2019.11.003..Zhuang H, Zhang R, Shu QM, et alProtective effect of human umbilical cord mesenchymal stem cells on light-damaged retinal pigment epithelial cells[J]. Chin J Exp Ophthalmol20193711863869. DOI:10.3760/cma.j.issn.2095-0160.2019.11.003.
3. Da Cruz L, Fynes K, Georgiadis O, et alPhase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration[J]. Nat Biotechnol2018364328337. DOI: 10.1038/nbt.4114.
4. Srinivasan M, Ravindran RD, O'Brien KS, et alAntioxidant vitamins for cataracts: 15-year follow-up of a randomized trial[J]. Ophthalmology20201277986987. DOI:10.1016/j.ophtha.2020.01.050.
5. Kassumeh S, Wertheimer CM, Ohlmann A, et alCytoprotective effect of crocin and trans-resveratrol on photodamaged primary human retinal pigment epithelial cells[J]. Eur J Ophthalmol2021312630637. DOI: 10.1177/1120672119895967.
6. 于万芹, 杜晓娜, 刘巧敏, 等罗汉果皂苷对妊娠糖尿病大鼠氧化应激损伤影响[J]. 中国临床药理学杂志2019352127232727. DOI:10.13699/j.cnki.1001-6821.2019.21.021..Yu WQ, Du XN, Liu QM, et alEffects of Momordica grosvenori saponin on oxidative stress injury in gestational diabetic rats[J]. Chin J Clin Pharmacol2019352127232727. DOI:10.13699/j.cnki.1001-6821.2019.21.021.
7. 潘晶, 杜月光, 郭燚三七皂苷对TGF-β1诱导的大鼠肾小管上皮细胞EMT的影响[J]. 中国实验方剂学杂志20192568994. DOI:10.13422/j.cnki.syfjx.20190636..Pan J, Du YG, Guo YEffect of panax notoginseng saponins on EMT of rat renal proximal tubular epithelial cells induced by TGF-β1[J]. Chin J Exper Tradit Medl Formul20192568994. DOI:10.13422/j.cnki.syfjx.20190636.
8. Sun J, Chen J, Li T, et al. ROS production and mitochondrial dysfunction driven by PU. 1-regulated NOX4-p22phox activation in Aβ-induced retinal pigment epithelial cell injury[J]. Theranostics, 2020, 10(25): 11637-11655. DOI: 10.7150/thno.48064. doi:10.7150/thno.48064..
9. Wang K, Zheng M, Lester KL, et alLight-induced Nrf2-/-mice as atrophic age-related macular degeneration model and treatment with nanoceria laden injectable hydrogel[J]. Sci Rep20199114573. DOI: 10.1038/s41598-019-51151-7. doi:10.1038/s41598-019-51151-7.
10. 张惟, 杨婧, 陈松, 等氧化应激下视网膜色素上皮细胞外泌体对视网膜色素上皮细胞血管内皮生长因子A及丝氨酸/苏氨酸激酶表达的影响[J]. 中华眼底病杂志20173315761. DOI:10.3760/cma.j.issn.1005-1015.2017.01.015..Zhang W, Yang J, Chen S, et alInfluence of oxidative stress-induced exosomes on Akt and vascular endothelial growth faetor-A of retinal pigment epithelium cells[J]. Chin J Ocul Fundus Dis20173315761. DOI:10.3760/cma.j.issn.1005-1015.2017.01.015.
11. Li X, Wang Q, Ren Y, et alTetramethylpyrazine protects retinal ganglion cells against H2O2-induced damage via the microRNA-182/mitochondrial pathway[J]. Int J Mol Med2019442503512. DOI: 10.3892/ijmm.2019.4214. doi:10.3892/ijmm.2019.4214.
12. Cui R, Tian L, Lu D, et alExendin-4 protects human retinal pigment epithelial cells from H₂O₂-induced oxidative damage via activation of NRF2 signaling[J]. Ophthalmic Res2020634404412. DOI:10.1159/000504891. doi:10.1159/000504891.
13. Hwang N, Kwon MY, Woo JM, et alOxidative stress-induced pentraxin 3 expression human retinal pigment epithelial cells is involved in the pathogenesis of age-related macular degeneration[J]. Int J Mol Sci201920236028. DOI: 10.3390/ijms20236028.
14. Balan DJ, Rajavel T, Das M, et alThymol induces mitochondrial pathway-mediated apoptosis via ROS generation, macromolecular damage and SOD diminution in A549 cells[J]. Pharmacol Rep2021731240254. DOI: 10.1007/s43440-020-00171-6.
15. Ekin S, Yildiz H, Alp HHNOX4, MDA, IMA and oxidative DNA damage: can these parameters be used to estimate the presence and severity of OSA?[J]. Sleep Breath2021251529536. DOI: 10.1007/s11325-020-02093-2.
16. Xiao R, Liao W, Luo G, et alModulation of gut microbiota composition and short-chain fatty acid synthesis by mogroside V in an in vitro incubation system[J]. ACS Omega20216392548625496. DOI: 10.1021/acsomega.1c03485.
17. 黄文蔚, 洪李锋, 郭璠, 等罗汉果皂苷对阿霉素心肌损伤大鼠氧化应激和凋亡调节作用研究[J]. 辽宁中医药大学学报20192163942. DOI: 10.13194/j.issn.1673-842x.2019.06.010..Huang WW, Hong LF, Guo P, et alEffect of mogmside on oxidative stress and cell apoptosis in myocardium of adriamycin myocardial injury rat[J]. J Liaoning Univ Tradit Chine Med20192163942. DOI: 10.13194/j.issn.1673-842x.2019.06.010.
18. Li Y, Zou L, Li T, et alMogroside V inhibits LPS-induced COX-2 expression/ROS production and overexpression of HO-1 by blocking phosphorylation of AKT1 in RAW264.7 cells[J]. Acta Biochim Biophys Sin (Shanghai)2019514365374. DOI:10.1093/abbs/gmz014.
19. Luo Y, Lu S, Gao Y, et alAraloside C attenuates atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy[J]. Aging (Albany NY)202012217041724. DOI: 10.18632/aging.102708.
20. Abozaid OAR, Sallam MW, El-Sonbaty S, et alResveratrol-selenium nanoparticles alleviate neuroinflammation and neurotoxicity in a rat model of Alzheimer's disease by regulating sirt1/miRNA-134/GSK3β expression[J]. Biol Trace Elem Res20222001251045114. DOI: 10.1007/s12011-021-03073-7.
21. Wang H, Su X, Zhang QQ, et alMicroRNA-93-5p participates in type 2 diabetic retinopathy through targeting Sirt1[J]. Int Ophthalmol2021411138373848. DOI: 10.1007/s10792-021-01953-4.
22. Xiu C, Jiang J, Song RExpression of miR-34a in cataract rats and its related mechanism[J]. Exp Ther Med202019210511057. DOI: 10.3892/etm.2019.8295.
23. Patruno A, Costantini E, Ferrone A, et alShort ELF-EMF exposure targets SIRT1/Nrf2/HO-1 signaling in THP-1 cells[J]. Int J Mol Sci202021197284. DOI: 10.3390/ijms21197284.
24. Wang G, Xie X, Yuan L, et alResveratrol ameliorates rheumatoid arthritis via activation of SIRT1-Nrf2 signaling pathway[J]. Biofactors2020463441453. DOI: 10.1002/biof.1599.
25. Samimi F, Baazm M, Eftekhar E, et alPossible antioxidant mechanism of coenzyme Q10 in diabetes: impact on Sirt1/Nrf2 signaling pathways[J]. Res Pharm Sci2019146524533. doi:10.4103/1735-5362.272561.

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Chinese Journal of Ocular Fundus Diseases

Mogroside regulates the oxidative stress response of retinal pigment epithelial cells induced by H₂O₂ through silent information regulator of transcription 1/nuclear factor erythroid-2-related actor 2 signaling pathway

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Chinese Journal of Ocular Fundus Diseases

Mogroside regulates the oxidative stress response of retinal pigment epithelial cells induced by H2O2 through silent information regulator of transcription 1/nuclear factor erythroid-2-related actor 2 signaling pathway

Abstract Full text Figures/Tables Video References Cited by

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Mogroside regulates the oxidative stress response of retinal pigment epithelial cells induced by H₂O₂ through silent information regulator of transcription 1/nuclear factor erythroid-2-related actor 2 signaling pathway