Journal of Ginseng Research

  • 제47권2호
  • /
  • Pages.311-318
  • /
  • 2023
  • /
  • 1226-8453(pISSN)
  • /
  • 2093-4947(eISSN)
고려인삼학회 (The Korean Society of Ginseng)
권호 표지
DOI QR코드

DOI QR Code

Nrf2-mediated activation of HO-1 is required in the blocking effect of compound K, a ginseng saponin metabolite, against oxidative stress damage in ARPE-19 human retinal pigment epithelial cells

  • Cheol, Park (Division of Basic Sciences, Dong-eui University) ;
  • Hee-Jae, Cha (College of Medicine, Kosin University) ;
  • Kyoung-Seob, Song (College of Medicine, Kosin University) ;
  • Heui-Soo, Kim (Department of Biological Sciences, Pusan National University) ;
  • EunJin, Bang (Anti-Aging Research Center and Department of Biochemistry, Dong-eui University College of Korean Medicine) ;
  • Hyesook, Lee (Department of Convergence Medicine, Pusan National University) ;
  • Cheng-Yun, Jin (College of Pharmacy, Zhengzhou University) ;
  • Gi-Young, Kim (Department of Marine Life Science, Jeju National University) ;
  • Yung Hyun, Choi (Anti-Aging Research Center and Department of Biochemistry, Dong-eui University College of Korean Medicine)
  • 투고 : 2022.05.02
  • 심사 : 2022.09.27
  • 발행 : 2023.03.02
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Background: The beneficial effects of compound K (CK) on different chronic diseases have been shown to be at least related to antioxidant action. Nevertheless, since its antioxidant activity in human retinal pigment epithelial (RPE) cells is still unknown, here we investigated whether CK alleviates oxidative stress-stimulated damage in RPE ARPE-19 cells. Methods: The cytoprotective consequence of CK in hydrogen peroxide (H2O2)-treated cells was evaluated by cell viability, DNA damage, and apoptosis assays. Fluorescence analysis and immunoblotting were performed to investigate the inhibitory action of CK on reactive oxygen species (ROS) production and mitochondrial dysfunction. Results: H2O2-promoted cytotoxicity, oxidative stress, DNA damage, mitochondrial impairment, and apoptosis were significantly attenuated by CK in ARPE-19 cells. Furthermore, nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation level and its shuttling to the nucleus were increased, which was correlated with upregulated activation of heme oxygenase-1 (HO-1). However, zinc protoporphyrin, a blocker of HO-1, significantly abrogated the preventive action of CK in H2O2-treated ARPE-19 cells. Conclusion: This study indicates that activation of Nrf2/HO-1 signaling by CK plays an important role in rescuing ARPE-19 cells from oxidative cellular damage.

키워드

과제정보

This research was funded by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2021R1A2C200954911).

참고문헌

  1. Ao J, Wood JP, Chidlow G, Gillies MC, Casson RJ. Retinal pigment epithelium in the pathogenesis of age-related macular degeneration and photobiomodulation as a potential therapy? Clin Exp Ophthalmol 2018;46:670-86. https://doi.org/10.1111/ceo.13121
  2. Sadda SR, Guymer R, Mones JM, Tufail A, Jaffe GJ. Anti-vascular endothelial growth factor use and atrophy in neovascular age-related macular degeneration: systematic literature review and expert Opinion. Ophthalmology 2020;127:648-59. https://doi.org/10.1016/j.ophtha.2019.11.010
  3. Eells JT. Mitochondrial dysfunction in the aging retina. Biology (Basel) 2019;8:31.
  4. Brook N, Brook E, Dharmarajan A, Chan A, Dass CR. The role of pigment epithelium-derived factor in protecting against cellular stress. Free Radic Res 2019;53:1166-80. https://doi.org/10.1080/10715762.2019.1697809
  5. Chopra P, Chhillar H, Kim YJ, Jo IH, Kim ST, Gupta R. Phytochemistry of ginsenosides: recent advancements and emerging roles. Crit Rev Food Sci Nutr 2021;19:1-28.
  6. de Oliveira Zanuso B, de Oliveira Dos Santos AR, Miola VFB, Guissoni Campos LM, Spilla CSG, Barbalho SM. Panax ginseng and aging related disorders: a systematic review. Exp Gerontol 2022;161:111731.
  7. Wan Y, Wang J, Xu JF, Tang F, Chen L, Tan YZ, Rao CL, Ao H, Peng C. Panax ginseng and its ginsenosides: potential candidates for the prevention and treatment of chemotherapy-induced side effects. J Ginseng Res 2021;45:617-30. https://doi.org/10.1016/j.jgr.2021.03.001
  8. Sodrul IMD, Wang C, Chen X, Du J, Sun H. Role of ginsenosides in reactive oxygen species-mediated anticancer therapy. Oncotarget 2017;9:2931-50. https://doi.org/10.18632/oncotarget.23407
  9. Ratan ZA, Haidere MF, Hong YH, Park SH, Lee JO, Lee J, Cho JY. Pharmacological potential of ginseng and its major component ginsenosides. J Ginseng Res 2021;45:199-210. https://doi.org/10.1016/j.jgr.2020.02.004
  10. Li CP, Qin G, Shi RZ, Zhang MS, Lv JY. Ginsenoside Rg1 reduces toxicity of PM2.5 on human umbilical vein endothelial cells by upregulating intracellular antioxidative state. Environ Toxicol Pharmacol 2013;35:21-9. https://doi.org/10.1016/j.etap.2012.11.006
  11. Li L, Du G, Wang D, Zhou J, Jiang G, Jiang H. Overexpression of heme oxygenase-1 in mesenchymal stem cells augments their protection on retinal cells in vitro and attenuates retinal ischemia/reperfusion injury in vivo against oxidative stress. Stem Cells Int 2017;2017:4985323.
  12. Li J, Liu D, Wu J, Zhang D, Cheng B, Zhang Y, Yin Z, Wang Y, Du J, Ling C. Ginsenoside Rg1 attenuates ultraviolet B-induced glucocortisides resistance in keratinocytes via Nrf2/HDAC2 signalling. Sci Rep 2016;6:39336.
  13. Gao Y, Chu S, Shao Q, Zhang M, Xia C, Wang Y, Li Y, Lou Y, Huang H, Chen N. Antioxidant activities of ginsenoside Rg1 against cisplatin-induced hepatic injury through Nrf2 signaling pathway in mice. Free Radic Res 2017;51:1-13. https://doi.org/10.1080/10715762.2016.1234710
  14. Yao Y, Hu S, Zhang C, Zhou Q, Wang H, Yang Y, Liu C, Ding H. Ginsenoside Rd attenuates cerebral ischemia/reperfusion injury by exerting an anti-pyroptotic effect via the miR-139-5p/FoxO1/Keap1/Nrf2 axis. Int Immunopharmacol 2022;105:108582.
  15. Nguyen TLL, Huynh DTN, Jin Y, Jeon H, Heo KS. Protective effects of ginsenoside-Rg2 and -Rh1 on liver function through inhibiting TAK1 and STAT3-mediated inflammatory activity and Nrf2/ARE-mediated antioxidant signaling pathway. Arch Pharm Res 2021;44:241-52. https://doi.org/10.1007/s12272-020-01304-4
  16. Yang Q, Lin J, Zhang H, Liu Y, Kan M, Xiu Z, Chen X, Lan X, Li X, Shi X. Ginsenoside compound K regulates amyloid b via the Nrf2/Keap1 signaling pathway in mice with scopolamine hydrobromide-induced memory impairments. J Mol Neurosci 2019;67:62-71. https://doi.org/10.1007/s12031-018-1210-3
  17. Zhang G, Zhang M, Yu J, Kang L, Guan H. Ginsenoside Rg1 prevents H2O2-induced lens opacity. Curr Eye Res 2021;46:1159-65. https://doi.org/10.1080/02713683.2020.1869266
  18. Shi Q, Chen X, Sun G, Wang L, Cui L. Ginsenoside Rg1 protects human retinal pigment epithelial ARPE-19 cells from toxicity of high glucose by upregulation of miR-26a. Life Sci 2019;221:152-8. https://doi.org/10.1016/j.lfs.2019.02.021
  19. Tang CZ, Li KR, Yu Q, Jiang Q, Yao J, Cao C. Activation of Nrf2 by Ginsenoside Rh3 protects retinal pigment epithelium cells and retinal ganglion cells from UV. Free Radic Biol Med 2018;117:238-46. https://doi.org/10.1016/j.freeradbiomed.2018.02.001
  20. Kim M, Moon A. A curcumin analog CA-5f inhibits urokinase-type plasminogen activator and invasive phenotype of triple-negative breast cancer cells. Toxicol Res 2022;38:19-26. https://doi.org/10.1007/s43188-021-00112-2
  21. Noh Y, Ahn JH, Lee JW, Hong J, Lee TK, Kim B, Kim SS, Won MH. Brain factor-7 improves learning and memory deficits and attenuates ischemic brain damage by reduction of ROS generation in stroke in vivo and in vitro. Lab Anim Res 2020;36:24.
  22. Choi MJ, Mukherjee S, Yun JW. Loss of ADAMTS15 promotes browning in 3T3-L1 white adipocytes via activation of b3-adrenergic receptor. Biotechnol Bioprocess Eng 2021;26:188-200.
  23. Lee H, Kim DH, Kim JH, Park SK, Jeong JW, Kim MY, Hong SH, Song KS, Kim GY, Hyun JW, et al. Urban aerosol particulate matter promotes necrosis and autophagy via reactive oxygen species-mediated cellular disorders that are accompanied by cell cycle arrest in retinal pigment epithelial cells. Antioxidants (Basel) 2021;10:149.
  24. Volobaev VP, Serdyukova ES, Kalyuzhnaya EE, Schetnikova EA, Korotkova AD, Naik AA, Bach SN, Prosekov AY, Larionov AV. Investigation of the genotoxic effects of fluoride on a bone tissue model. Toxicol Res 2020;36:337-42. https://doi.org/10.1007/s43188-020-00039-0
  25. Liu Z, Ouyang G, Lu W, Zhang H. Long non-coding RNA HOTAIR promotes hepatocellular carcinoma progression by regulating miR-526b-3p/DHX33 axis. Genes Genomics 2021;43:857-68. https://doi.org/10.1007/s13258-021-01098-9
  26. Choi YH. Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of platycodin D against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts. Gen Physiol Biophys 2020;39:519-30. https://doi.org/10.4149/gpb_2020030
  27. Kang S, Siddiqi MH, Yoon SJ, Ahn S, Noh HY, Kumar NS, Kim YJ, Yang DC. Therapeutic potential of compound K as an IKK inhibitor with implications for osteoarthritis prevention: an in silico and in vitro study. Vitro Cell Dev Biol Anim 2016;52:895-905. https://doi.org/10.1007/s11626-016-0062-9
  28. Li X, Huang Q, Wang M, Yan X, Song X, Ma R, Jiang R, Zhao D, Sun L. Compound K inhibits autophagy-mediated apoptosis through activation of the PI3K-Akt signaling pathway thus protecting against ischemia/reperfusion injury. Cell Physiol Biochem 2018;47:2589-601. https://doi.org/10.1159/000491655
  29. Duan H, Zhang Q, Liu J, Li R, Wang D, Peng W, Wu C. Suppression of apoptosis in vascular endothelial cell, the promising way for natural medicines to treat atherosclerosis. Pharmacol Res 2021;168:105599.
  30. Huang Q, Lou T, Wang M, Xue L, Lu J, Zhang H, Zhang Z, Wang H, Jing C, Zhao D, et al. Compound K inhibits autophagy-mediated apoptosis induced by oxygen and glucose deprivation/reperfusion via regulating AMPK-mTOR pathway in neurons. Life Sci 2020;254:117793. https://doi.org/10.1016/j.lfs.2019.116816
  31. Cai BX, Luo D, Lin XF, Gao J. Compound K suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair in human keratinocytes. Arch Pharm Res 2008;31:1483-8. https://doi.org/10.1007/s12272-001-2134-x
  32. Hong Y, Liang YP, Chen WQ, You LX, Ni QF, Gao XY, Lin XR. Protective effects of upregulated HO-1 gene against the apoptosis of human retinal pigment epithelial cells in vitro. Int J Ophthalmol 2021;14:649-55. https://doi.org/10.18240/ijo.2021.05.03
  33. Senichkin VV, Pervushin NV, Zuev AP, Zhivotovsky B, Kopeina GS. Targeting Bcl-2 family proteins: what, where, when? Biochemistry (Mosc) 2020;85:1210-26. https://doi.org/10.1134/S0006297920100090
  34. Ulasov AV, Rosenkranz AA, Georgiev GP, Sobolev AS. Nrf2/Keap1/ARE signaling: towards specific regulation. Life Sci 2022;291:120111.
  35. Tavakkoli A, Iranshahi M, Hasheminezhad SH, Hayes AW, Karimi G. The neuroprotective activities of natural products through the Nrf2 upregulation. Phytother Res 2019;33:2256-73.  https://doi.org/10.1002/ptr.6427