Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Protective effects of Panax ginseng berry extract on blue light-induced retinal damage in ARPE-19 cells and mouse retina

  • Hye Mi, Cho (Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Sang Jun, Lee (Holistic Bio CO.) ;
  • Se-Young, Choung (Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University)
  • Received : 2021.11.01
  • Accepted : 2022.04.11
  • Published : 2023.01.02
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Age-related macular degeneration (AMD) is a significant visual disease that induces impaired vision and irreversible blindness in the elderly. However, the effects of ginseng berry extract (GBE) on the retina have not been studied. Therefore, this study aimed to investigate the protective effects of GBE on blue light (BL)-induced retinal damage and elucidate its underlying mechanisms in human retinal pigment epithelial cells (ARPE-19 cells) and Balb/c retina. Methods: To investigate the effects and underlying mechanisms of GBE on retinal damage in vitro, we performed cell viability assay, pre-and post-treatment of sample, reactive oxygen species (ROS) assay, quantitative real-time PCR (qRT-PCR), and western immunoblotting using A2E-laden ARPE-19 cells with BL exposure. In addition, Balb/c mice were irradiated with BL to induce retinal degeneration and orally administrated with GBE (50, 100, 200 mg/kg). Using the harvested retina, we performed histological analysis (thickness of retinal layers), qRT-PCR, and western immunoblotting to elucidate the effects and mechanisms of GBE against retinal damage in vivo. Results: GBE significantly inhibited BL-induced cell damage in ARPE-19 cells by activating the SIRT1/PGC-1α pathway, regulating NF-kB translocation, caspase 3 activation, PARP cleavage, expressions of apoptosis-related factors (BAX/BCL-2, LC3-II, and p62), and ROS production. Furthermore, GBE prevented BL-induced retinal degeneration by restoring the thickness of retinal layers and suppressed inflammation and apoptosis via regulation of NF-kB and SIRT1/PGC-1α pathway, cleavage of caspase 3 and PARP, and expressions of apoptosis-related factors in vivo. Conclusions: GBE could be a potential agent to prevent dry AMD and progression to wet AMD.

Keywords

References

  1. Pennington KL, DeAngelis MM. Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors. Eye Vision 2016;3:1-20.  https://doi.org/10.1186/s40662-015-0032-4
  2. Kuno N, Fujii S. Dry age-related macular degeneration: recent progress of therapeutic approaches. Curr Mol Pharmacol 2011;4:196-232.  https://doi.org/10.2174/1874467211104030196
  3. Bressler NM, Bressler SB, Fine SL. Age-related macular degeneration. Surv Ophthalmol 1988;32:375-413.  https://doi.org/10.1016/0039-6257(88)90052-5
  4. Grossniklaus HE, Green WR. Choroidal neovascularization. Am J Ophthalmol 2004;137:496-503.  https://doi.org/10.1016/j.ajo.2003.09.042
  5. Kauppinen A, Niskanen H, Suuronen T, Kinnunen K, Salminen A, Kaarniranta K. Oxidative stress activates NLRP3 inflammasomes in ARPE-19 cells-implications for age-related macular degeneration (AMD). Immunol Lett 2012;147:29-33.  https://doi.org/10.1016/j.imlet.2012.05.005
  6. Kennedy CJ, Rakoczy PE, Constable IJ. Lipofuscin of the retinal pigment epithelium: a review. Eye 1995;9:763-71.  https://doi.org/10.1038/eye.1995.192
  7. Sparrow JR, Fishkin N, Zhou J, Cai B, Jang YP, Krane S, Itagaki Y, Nakanishi K. A2E, a byproduct of the visual cycle. Vis Res 2003;43:2983-90.  https://doi.org/10.1016/S0042-6989(03)00475-9
  8. Sparrow JR, Nakanishi K, Parish CA. The lipofuscin fluorophore A2E mediates blue lighteinduced damage to retinal pigmented epithelial cells. Invest Ophthalmol Vis Sci 2000;41:1981-9. 
  9. Jang YP, Matsuda H, Itagaki Y, Nakanishi K, Sparrow JR. Characterization of peroxy-A2E and furan-A2E photooxidation products and detection in human and mouse retinal pigment epithelial cell lipofuscin. J Biol Chem2005;280:39732-9.  https://doi.org/10.1074/jbc.M504933200
  10. Arnault E, Barrau C, Nanteau C, Gondouin P, Bigot K, Vienot F, Gutman E, Fontaine V, Villette T, Cohen-Tannoudji D. Phototoxic action spectrum on a retinal pigment epithelium model of age-related macular degeneration exposed to sunlight normalized conditions. PLoS One 2013;8:e71398.  https://doi.org/10.1371/journal.pone.0071398
  11. Lambert NG, ElShelmani H, Singh MK, Mansergh FC, Wride MA, Padilla M, Keegan D, Hogg RE, Ambati BK. Risk factors and biomarkers of age-related macular degeneration. Prog Retin Eye Res 2016;54:64-102.  https://doi.org/10.1016/j.preteyeres.2016.04.003
  12. Shang Y-M, Wang G-S, Sliney D, Yang C-H, Lee L-L. White lighteemitting diodes (LEDs) at domestic lighting levels and retinal injury in a rat model. Environ Health Perspect 2014;122:269-76.  https://doi.org/10.1289/ehp.1307294
  13. Suzuki M, Tsujikawa M, Itabe H, Du Z-J, Xie P, Matsumura N, Fu X, Zhang R, Sonoda K-h, Egashira K. Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration. J Cell Sci 2012;125:2407-15.  https://doi.org/10.1242/jcs.097683
  14. Nakamura M, Kuse Y, Tsuruma K, Shimazawa M, Hara H. The involvement of the oxidative stress in murine blue LED light-induced retinal damage model. Biol Pharm Bull 2017;40:1219-25.  https://doi.org/10.1248/bpb.b16-01008
  15. Attele AS, Wu JA, Yuan C-S. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-93.  https://doi.org/10.1016/S0006-2952(99)00212-9
  16. Kim J, Cho SY, Kim SH, Kim S, Park C-W, Cho D, Seo DB, Shin SS. Ginseng berry and its biological effects as a natural phytochemical. Natural Products Chemistry & Research; 2016. 
  17. Kim C-K, Cho DH, Lee K-S, Lee D-K, Park C-W, Kim WG, Lee SJ, Ha K-S, Goo Taeg O, Kwon Y-G. Ginseng berry extract prevents atherogenesis via antiinflammatory action by upregulating phase II gene expression. Evid base Compl Alternative Med 2012;2012. 
  18. Kuo Y-H, Ikegami F, Lambein F. Neuroactive and other free amino acids in seed and young plants of Panax ginseng. Phytochemistry 2003;62:1087-91.  https://doi.org/10.1016/S0031-9422(02)00658-1
  19. Wang W, Zhao Y, Rayburn ER, Hill DL, Wang H, Zhang R. In vitro anti-cancer activity and structureeactivity relationships of natural products isolated from fruits of Panax ginseng. Cancer Chemother Pharmacol 2007;59:589-601.  https://doi.org/10.1007/s00280-006-0300-z
  20. Lee SY, Kim YK, Park NI, Kim CS, Lee CY, Park SU. Chemical constituents and biological activities of the berry of Panax ginseng. J Med Plants Res 2010;4:349-53. 
  21. Chung I-M, Lim J-J, Ahn M-S, Jeong H-N, An T-J, Kim S-H. Comparative phenolic compound profiles and antioxidative activity of the fruit, leaves, and roots of Korean ginseng (Panax ginseng Meyer) according to cultivation years. J Ginseng Res 2016;40:68-75.  https://doi.org/10.1016/j.jgr.2015.05.006
  22. Perez ZEJ, Ramya Mathiyalagan JM, Kim Y-J, Kang HM, Abbai R, Seo KH, Wang D, Soshnikova V, Yang DC. Ginseng-berry-mediated gold and silver nanoparticle synthesis and evaluation of their in vitro antioxidant, antimicrobial, and cytotoxicity effects on human dermal fibroblast and murine melanoma skin cell lines. Int J Nanomed 2017;12:709.  https://doi.org/10.2147/IJN.S118373
  23. Li KR, Zhang ZQ, Yao J, Zhao YX, Duan J, Cao C, Jiang Q. Ginsenoside Rg-1 protects retinal pigment epithelium (RPE) cells from cobalt chloride (CoCl2) and hypoxia assaults. PLoS One 2013;8:e84171.  https://doi.org/10.1371/journal.pone.0084171
  24. Bian M, Du X, Wang P, Cui J, Xu J, Gu J, Zhang T, Chen Y. Combination of ginsenoside Rb1 and Rd protects the retina against bright light-induced degeneration. Sci Rep 2017;7:6015.  https://doi.org/10.1038/s41598-017-06471-x
  25. Lee BL, Kang JH, Kim HM, Jeong SH, Jang DS, Jang YP, Choung SY. Polyphenolenriched Vaccinium uliginosum L. fractions reduce retinal damage induced by blue light in A2E-laden ARPE19 cell cultures and mice. Nutr Res (NY) 2016;36:1402-14.  https://doi.org/10.1016/j.nutres.2016.11.008
  26. Lee MY, Seo HS, Singh D, Lee SJ, Lee CH. Unraveling dynamic metabolomes underlying different maturation stages of berries harvested from Panax ginseng. J Ginseng Res 2020;44:413-23.  https://doi.org/10.1016/j.jgr.2019.02.002
  27. Joo K-M, Lee J-H, Jeon H-Y, Park C-W, Hong D-K, Jeong H-J, Lee SJ, Lee S-Y, Lim K-M. Pharmacokinetic study of ginsenoside Re with pure ginsenoside Re and ginseng berry extracts in mouse using ultra performance liquid chromatography/ mass spectrometric method. J Pharmaceut Biomed Anal 2010;51:278-83.  https://doi.org/10.1016/j.jpba.2009.08.013
  28. Kim J, Cho K, Choung SY. Protective effect of Prunella vulgaris var. L extract against blue light induced damages in ARPE-19 cells and mouse retina. Free Radic Biol Med 2020;152:622-31.  https://doi.org/10.1016/j.freeradbiomed.2019.12.003
  29. Kaarniranta K, Kajdanek J, Morawiec J, Pawlowska E, Blasiak J. PGC-1a protects RPE cells of the aging retina against oxidative stress-induced degeneration through the regulation of senescence and mitochondrial quality control. The significance for AMD pathogenesis. Int J Mol Sci 2018;19. 
  30. Yang H, Zhang W, Pan H, Feldser HG, Lainez E, Miller C, Leung S, Zhong Z, Zhao H, Sweitzer S, et al. SIRT1 activators suppress inflammatory responses through promotion of p65 deacetylation and inhibition of NF-kB activity. PLoS One 2012;7:-46364.  https://doi.org/10.1371/journal.pone.0046364
  31. Santos L, Escande C, Denicola A. Potential modulation of sirtuins by oxidative stress. Oxid Med Cell Longev 2016;2016:9831825.  https://doi.org/10.1155/2016/9831825
  32. Saadat KA, Murakami Y, Tan X, Nomura Y, Yasukawa T, Okada E, Ikeda Y, Yanagi Y. Inhibition of autophagy induces retinal pigment epithelial cell damage by the lipofuscin fluorophore A2E. FEBS Open Bio 2014;4:1007-14.  https://doi.org/10.1016/j.fob.2014.11.003
  33. Yamamoto Y, Gaynor RB. Role of the NF-kB pathway in the pathogenesis of human disease states. Curr Mol Med 2001;1:287-96.  https://doi.org/10.2174/1566524013363816
  34. Suarez-Barrio C, Del Olmo-Aguado S, Garcia-Perez E, Fernandez-Vega-Cueto L, Fernandez-Vega Cueto A, Baamonde-Arbaiza B, Fernandez-Vega L, Merayo-Lloves J. Plasma rich in growth factors promotes autophagy in ARPE19 cells in response to oxidative stress induced by blue light. Biomolecules 2021:11. 
  35. Okamoto T, Ozawa Y, Kamoshita M, Osada H, Toda E, Kurihara T, Nagai N, Umezawa K, Tsubota K. The neuroprotective effect of rapamycin as a modulator of the mTOR-NF-kB Axis during retinal inflammation. PLoS One 2016;11:-0146517.  https://doi.org/10.1371/journal.pone.0146517
  36. Jurgensmeier JM, Xie Z, Deveraux Q, Ellerby L, Bredesen D, Reed JC. Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci Unit States Am 1998;95:4997-5002.  https://doi.org/10.1073/pnas.95.9.4997
  37. Chaitanya GV, Steven AJ, Babu PP. PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration. Cell Commun Signal : CCS 2010;8:31.  https://doi.org/10.1186/1478-811X-8-31
  38. Jeong SY, Gu X, Jeong KW. Photoactivation of N-retinylidene-N-retinylethanolamine compromises autophagy in retinal pigmented epithelial cells. Food Chem Toxicol 2019;131:110555.  https://doi.org/10.1016/j.fct.2019.06.002
  39. Kaarniranta K, Tokarz P, Koskela A, Paterno J, Blasiak J. Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration. Cell Biol Toxicol 2017;33:113-28.  https://doi.org/10.1007/s10565-016-9371-8
  40. Liu J, Copland DA, Theodoropoulou S, Chiu HA, Barba MD, Mak KW, Mack M, Nicholson LB, Dick AD. Impairing autophagy in retinal pigment epithelium leads to inflammasome activation and enhanced macrophage-mediated angiogenesis. Sci Rep 2016;6:20639.  https://doi.org/10.1038/srep20639
  41. Mitter SK, Song C, Qi X, Mao H, Rao H, Akin D, Lewin A, Grant M, Dunn Jr W, Ding J. Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD. Autophagy 2014;10:1989-2005.  https://doi.org/10.4161/auto.36184
  42. Xia H, Hu Q, Li L, Tang X, Zou J, Huang L, Li X. Protective effects of autophagy against blue light-induced retinal degeneration in aged mice. Sci China Life Sci 2019;62:244-56.  https://doi.org/10.1007/s11427-018-9357-y
  43. Ma L, Lin XM. Effects of lutein and zeaxanthin on aspects of eye health. J Sci Food Agric 2010;90:2-12. https://doi.org/10.1002/jsfa.3785