Journal of Microbiology and Biotechnology

  • 제34권3호
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  • Pages.596-605
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  • 2024
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  • 1017-7825(pISSN)
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  • 1738-8872(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
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Anthocyanins Inhibits Oxidative Injury in Human Retinal Pigment Epithelial ARPE-19 Cells via Activating Heme Oxygenase-1

  • Cheol Park (Division of Basic Sciences, College of Liberal Studies, Dong-eui University) ;
  • Hyun Hwangbo (Anti-Aging Research Center, Dong-eui University) ;
  • Sung Ok Kim (Department of Food Science and Biotechnology, College of Engineering, Kyungsung University) ;
  • Jeong Sook Noh (Department of Food Science & Nutrition, Tongmyong University) ;
  • Shin-Hyung Park (Department of Pathology, Dong-eui University College of Korean Medicine) ;
  • Su Hyun Hong (Anti-Aging Research Center, Dong-eui University) ;
  • Sang Hoon Hong (Department of Internal Medicine, Dong-eui University College of Korean Medicine) ;
  • Gi-Young Kim (Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University) ;
  • Yung Hyun Choi (Anti-Aging Research Center, Dong-eui University)
  • 투고 : 2023.10.10
  • 심사 : 2023.11.02
  • 발행 : 2024.03.28
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초록

Anthocyanins belong to phenolic pigments and are known to have various pharmacological activities. This study aimed to investigate whether anthocyanins could inhibit hydrogen peroxide (H2O2)-induced oxidative damage in human retinal pigment epithelial ARPE-19 cells. Our results indicated that anthocyanins suppressed H2O2-induced genotoxicity, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione. Anthocyanins also suppressed H2O2-induced apoptosis by reversing the Bcl-2/Bax ratio and inhibiting caspase-3 activation. Additionally, anthocyanins attenuated the release of cytochrome c into the cytosol, which was achieved by interfering with mitochondrial membrane disruption. Moreover, anthocyanins increased the expression of heme oxygenase-1 (HO-1) as well as its activity, which was correlated with the phosphorylation and nuclear translocation of nuclear factor-erythroid-2 related factor 2 (Nrf2). However, the cytoprotective and anti-apoptotic effects of anthocyanins were significantly attenuated by the HO-1 inhibitor, demonstrating that anthocyanins promoted Nrf2-induced HO-1 activity to prevent ARPE-19 cells from oxidative stress. Therefore, our findings suggest that anthocyanins, as Nrf2 activators, have potent ROS scavenging activity and may have the potential to protect ocular injury caused by oxidative stress.

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과제정보

This research was funded by Basic Science Research Program through the National Research Foundation of Korea (NRF) grant funded by the Korea government (2021R1A2C2009549) and Korea Basic Science Institute grant (NRF-2020R1A6C101A201).

참고문헌

  1. Fang J. 2015. Classification of fruits based on anthocyanin types and relevance to their health effects. Nutrition 31: 1301-1306. 
  2. Sasaki N, Nishizaki Y, Ozeki Y, Miyahara T. 2014. The role of acyl-glucose in anthocyanin modifications. Molecules 19: 18747-18766. 
  3. He J, Ye S, Correia P, Fernandes I, Zhang R, Wu M, et al. 2022. Dietary polyglycosylated anthocyanins, the smart option? A comprehensive review on their health benefits and technological applications. Compr. Rev. Food Sci. Food Saf. 21: 3096-3128. 
  4. Saigo T, Wang T, Watanabe M, Tohge T. 2020. Diversity of anthocyanin and proanthocyanin biosynthesis in land plants. Curr. Opin. Plant Biol. 55: 93-99. 
  5. Vahapoglu B, Erskine E, Gultekin Subasi B, Capanoglu E. 2021. Recent studies on berry bioactives and their health-promoting roles. Molecules 27: 108. 
  6. Panchal SK, John OD, Mathai ML, Brown L. 2022. Anthocyanins in chronic diseases: the power of purple. Nutrients 14: 2161. 
  7. Khoo HE, Ng HS, Yap WS, Goh HJH, Yim HS. 2019. Nutrients for prevention of macular degeneration and eye-related diseases. Antioxidants (Basel) 8: 85. 
  8. Martini D, Marino M, Venturi S, Tucci M, Klimis-Zacas D, Riso P, et al. 2023. Blueberries and their bioactives in the modulation of oxidative stress, inflammation and cardio/vascular function markers: a systematic review of human intervention studies. J. Nutr. Biochem. 111: 109154. 
  9. Bocsan IC, Magureanu DC, Pop RM, Levai AM, Macovei sO, Patrasca IM, et al. 2022. Antioxidant and anti-inflammatory actions of polyphenols from red and white grape pomace in ischemic heart diseases. Biomedicines 10: 2337. 
  10. Perez-Torres I, Castrejon-Tellez V, Soto ME, Rubio-Ruiz ME, Manzano-Pech L, Guarner-Lans V. 2021. Oxidative stress, plant natural antioxidants, and obesity. Int. J. Mol. Sci. 22: 1786. 
  11. Chen J, Meng X. 2022. Aronia melanocarpa anthocyanin extracts improve hepatic structure and function in high-fat diet-/streptozotocin-induced T2DM mice. J. Agric. Food Chem. 70: 11531-11543. 
  12. Wang C, Yu S, Jiang J, Li H, Pan Y, Li W, et al. 2022. Protective effect of anthocyanins on radiation-induced hippocampal injury through activation of SIRT3. Curr. Pharm. Des. 28: 1103-1108. 
  13. Molagoda IMN, Lee KT, Choi YH, Kim GY. 2020. Anthocyanins from Hibiscus syriacus L. inhibit oxidative stress-mediated apoptosis by activating the Nrf2/HO-1 signaling pathway. Antioxidants (Basel) 9: 42. 
  14. Yin L, Fan SJ, Zhang MN. 2022. Protective effects of anthocyanins extracted from Vaccinium uliginosum on 661W cells against microwave-induced retinal damage. Chin. J. Integr. Med. 28: 620-626. 
  15. Thummayot S, Tocharus C, Jumnongprakhon P, Suksamrarn A, Tocharus J. 2018. Cyanidin attenuates Aβ25-35-induced neuroinflammation by suppressing NF-kB activity downstream of TLR4/NOX4 in human neuroblastoma cells. Acta Pharmacol. Sin. 39: 1439-1452. 
  16. Ali T, Kim T, Rehman SU, Khan MS, Amin FU, Khan M, et al. 2018. Natural dietary supplementation of anthocyanins via PI3K/Akt/Nrf2/HO-1 pathways mitigate oxidative stress, neurodegeneration, and memory impairment in a mouse model of Alzheimer's disease. Mol. Neurobiol. 55: 6076-6093. 
  17. Song Y, Huang L, Yu J. 2016. Effects of blueberry anthocyanins on retinal oxidative stress and inflammation in diabetes through Nrf2/HO-1 signaling. J. Neuroimmunol. 301: 1-6. 
  18. Shaw P, Chattopadhyay A. 2020. Nrf2-ARE signaling in cellular protection: mechanism of action and the regulatory mechanisms. J. Cell. Physiol. 235: 3119-3130. 
  19. Jenkins T, Gouge J. 2021. Nrf2 in cancer, detoxifying enzymes and cell death programs. Antioxidants (Basel) 10: 1030. 
  20. Yu ZY, Ma D, He ZC, Liu P, Huang J, Fang Q, et al. 2018. Heme oxygenase-1 protects bone marrow mesenchymal stem cells from iron overload through decreasing reactive oxygen species and promoting IL-10 generation. Exp. Cell Res. 362: 28-42. 
  21. Peng W, Wu Y, Peng Z, Qi W, Liu T, Yang B, et al. 2022. Cyanidin-3-glucoside improves the barrier function of retinal pigment epithelium cells by attenuating endoplasmic reticulum stress-induced apoptosis. Food Res. Int. 157: 111313. 
  22. Ni T, Yang W, Xing Y. 2019. Protective effects of delphinidin against H2O2-induced oxidative injuries in human retinal pigment epithelial cells. Biosci. Rep. 39: BSR20190689. 
  23. Park C, Lee WS, Go SI, Jeong SH, Yoo J, Cha HJ, et al. 2021. Apoptotic effects of anthocyanins from Vitis coignetiae Pulliat are enhanced by augmented enhancer of the rudimentary homolog (ERH) in human gastric carcinoma MKN28 cells. In. J. Mol. Sci. 22: 3030. 
  24. Han MH, Kim HJ, Jeong JW, Park C, Kim BW, Choi YH. 2018. Inhibition of adipocyte differentiation by anthocyanins isolated from the fruit of Vitis coignetiae Pulliat is associated with the activation of AMPK signaling pathway. Toxicol. Res. 34: 13-21. 
  25. Lu JN, Lee WS, Kim MJ, Yun JW, Jung JH, Yi SM, et al. 2014. The inhibitory effect of anthocyanins on Akt on invasion and epithelial-mesenchymal transition is not associated with the anti-EGFR effect of the anthocyanins. Int. J. Oncol. 44: 1756-1766. 
  26. Yun JW, Lee WS, Kim MJ, Lu JN, Kang MH, Kim HG, et al. 2010. Characterization of a profile of the anthocyanins isolated from Vitis coignetiae Pulliat and their anti-invasive activity on HT-29 human colon cancer cells. Food Chem. Toxicol. 48: 903-909. 
  27. Shin DY, Lee WS, Lu JN, Kang MH, Ryu CH, Kim GY, et al. 2009. Induction of apoptosis in human colon cancer HCT-116 cells by anthocyanins through suppression of Akt and activation of p38-MAPK. Int. J. Oncol. 35: 1499-504. 
  28. Park C, Noh JS, Jung Y, Leem SH, Hyun JW, Chang YC, et al. 2022. Fisetin attenuated oxidative stress-induced cellular damage in ARPE-19 human retinal pigment epithelial cells through Nrf2-mediated activation of heme oxygenase-1. Front. Pharmacol. 13: 927898. 
  29. Jeong MJ, Lim DS, Kim SO, Park C, Leem SH, Lee H, et al. 2022. Protection of oxidative stress-induced DNA damage and apoptosis by rosmarinic acid in murine myoblast C2C12 cells. Biotechnol. Bioprocess Eng. 27: 171-182. 
  30. Mukherjee S, Park JP, Yun JW. 2022. Carboxylesterase3 (Ces3) Interacts with bone morphogenetic protein 11 and promotes differentiation of osteoblasts via Smad1/5/9 pathway. Biotechnol. Bioprocess Eng. 27: 1-16. 
  31. Choi YH. 2022. Tacrolimus induces apoptosis in leukemia Jurkat cells through inactivation of the reactive oxygen species-dependent phosphoinositide-3-kinase/Akt signaling pathway. Biotechnol. Bioprocess Eng. 27: 183-192. 
  32. Sukjamnong S, Chen H, Saad S, Santiyanont R. 2022. Fimbristylis ovata and Artemisia vulgaris extracts inhibited AGE-mediated RAGE expression, ROS generation, and inflammation in THP-1 cells. Toxicol. Res. 38: 331-343. 
  33. Park C, Lee H, Hong SH, Kim JH, Park SK, Jeong JW, et al. 2019. Protective effect of diphlorethohydroxycarmalol against oxidative stress-induced DNA damage and apoptosis in retinal pigment epithelial cells. Cutan. Ocul. Toxicol. 38: 298-308. 
  34. Hernandez M, Recalde S, Gonzalez-Zamora J, Bilbao-Malave V, Saenz de Viteri M, Bezunartea J, et al. 2021. Anti-inflammatory and anti-oxidative synergistic effect of vitamin D and nutritional complex on retinal pigment epithelial and endothelial cell lines against age-related macular degeneration. Nutrients 13: 1423. 
  35. Mahendra CK, Tan LTH, Pusparajah P, Htar TT, Chuah LH, Lee VS, et al. 2020. Detrimental effects of UVB on retinal pigment epithelial cells and its role in age-related macular degeneration. Oxid. Med. Cell. Longev. 2020: 1904178. 
  36. Tong Y, Zhang Z, Wang S. 2022. Role of mitochondria in retinal pigment epithelial aging and degeneration. Front. Aging 3: 926627. 
  37. Cordelli E, Bignami M, Pacchierotti F. 2021. Comet assay: a versatile but complex tool in genotoxicity testing. Toxicol. Res. (Camb.) 10: 68-78. 
  38. Kopp B, Khoury L, Audebert M. 2019. Validation of the γH2AX biomarker for genotoxicity assessment: a review. Arch. Toxicol. 93: 2103-2114. 
  39. Hahm JY, Park J, Jang ES, Chi SW. 2022. 8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification. Exp. Mol. Med. 54: 1626-1642. 
  40. Lou MF. 2022. Glutathione and glutaredoxin in redox regulation and cell signaling of the lens. Antioxidants (Basel) 11: 1973. 
  41. Enns GM, Cowan TM. 2017. Glutathione as a redox biomarker in mitochondrial disease-implications for therapy. J. Clin. Med. 6: 50. 
  42. Wang Y, Zhang D, Liu Y, Wang D, Liu J, Ji B. 2015. The protective effects of berry-derived anthocyanins against visible light-induced damage in human retinal pigment epithelial cells. J. Sci. Food d Agric. 95: 936-944. 
  43. Tiwari S, Dewry RK, Srivastava R, Nath S, Mohanty TK. 2022. Targeted antioxidant delivery modulates mitochondrial functions, ameliorates oxidative stress and preserve sperm quality during cryopreservation. Theriogenology 179: 22-31. 
  44. Bock FJ, Tait SWG. 2020. Mitochondria as multifaceted regulators of cell death. Nat. Rev. Mol. Cell Biol. 21: 85-100. 
  45. Kiraz Y, Adan A, Kartal Yandim M. Baran Y. 2016. Major apoptotic mechanisms and genes involved in apoptosis. Tumor Biol. 37: 8471-8486. 
  46. Clementi ME, Pizzoferrato M, Bianchetti G, Brancato A, Sampaolese B, Maulucci G, et al. 2022. Cytoprotective effect of idebenone through modulation of the intrinsic mitochondrial pathway of apoptosis in human retinal pigment epithelial cells exposed to oxidative stress induced by hydrogen peroxide. Biomedicines 10: 503. 
  47. Dinc E, Ayaz L, Kurt AH. 2017. Protective effect of combined caffeic acid phenethyl ester and bevacizumab against hydrogen peroxide-induced oxidative stress in human RPE cells. Curr. Eye Res. 42: 1659-1666. 
  48. Lalier L, Vallette F, Manon S. 2022. Bcl-2 Family members and the mitochondrial import machineries: the roads to death. Biomolecules 12: 162. 
  49. Du Y, You L, Ni B, Sai N, Wang W, Sun M, et al. 2020. Phillyrin mitigates apoptosis and oxidative stress in hydrogen peroxide-treated RPE cells through activation of the Nrf2 signaling pathway. Oxid. Med. Cell. Longev. 2020: 2684672. 
  50. You L, Peng H, Liu J, Cai M, Wu H, Zhang Z, et al. 2021. Catalpol protects ARPE-19 cells against oxidative stress via activation of the Keap1/Nrf2/ARE pathway. Cells 10: 2635.