본문 바로가기
KERD
논문KCI 등재

Anthocyanins Inhibits Oxidative Injury in Human Retinal Pigment Epithelial ARPE-19 Cells via Activating Heme Oxygenase-1

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류생물학

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.

Abstract

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.

참고문헌 (50)

  1. Fang J, "Classification of fruits based on anthocyanin types and relevance to their health effects", Nutrition, 31, pp.1301~1306 (2015)
  2. Sasaki N, "The role of acyl-glucose in anthocyanin modifications", Molecules, 19, pp.18747~18766 (2014)
  3. He J, "Dietary polyglycosylated anthocyanins, the smart option? A comprehensive review on their health benefits and technological applications", Compr. Rev. Food Sci. Food Saf, 21, pp.3096~3128 (2022)
  4. Saigo T, "Diversity of anthocyanin and proanthocyanin biosynthesis in land plants", Curr. Opin. Plant Biol, 55, pp.93~99 (2020)
  5. Vahapoglu B, "Recent studies on berry bioactives and their health-promoting roles", Molecules, 27, pp.108~ (2021)
  6. Panchal SK, "Anthocyanins in chronic diseases : the power of purple", Nutrients, 14, pp.2161~ (2022)
  7. Khoo HE, "Nutrients for prevention of macular degeneration and eye-related diseases", Antioxidants(Basel), 8, pp.85~ (2019)
  8. Martini D, "Blueberries and their bioactives in the modulation of oxidative stress, inflammation and cardio", vascular function markers : a systematic review of human intervention studies, 2023, pp.111, 109154~
  9. Bocsan IC, "Antioxidant and anti-inflammatory actions of polyphenols from red and white grape pomace in ischemic heart diseases", Biomedicines, 10, pp.2337~ (2022)
  10. Pérez-Torres I, "Oxidative stress, plant natural antioxidants, and obesity", Int. J. Mol. Sci, 22, pp.1786~ (2021)
  11. Chen J, "Aronia melanocarpa anthocyanin extracts improve hepatic structure and function in high-fat diet-", streptozotocin-induced T2DM mice, 2022, pp.70, 11531~11543
  12. Wang C, "Protective effect of anthocyanins on radiation-induced hippocampal injury through activation of SIRT3", Curr. Pharm. Des, 28, pp.1103~1108 (2022)
  13. Molagoda IMN, "Anthocyanins from Hibiscus syriacus L. inhibit oxidative stress-mediated apoptosis by activating the Nrf2", HO-1 signaling pathway, 2020, pp.9, 42~
  14. Yin L, "Protective effects of anthocyanins extracted from Vaccinium uliginosum on 661W cells against microwave-induced retinal damage", Chin. J. Integr. Med, 28, pp.620~626 (2022)
  15. Thummayot S, "Cyanidin attenuates Aβ25-35-induced neuroinflammation by suppressing NF-kB activity downstream of TLR4", NOX4 in human neuroblastoma cells, 2018, pp.39, 1439~1452
  16. Ali T, "Natural dietary supplementation of anthocyanins via PI3K", Akt, HO-1 pathways mitigate oxidative stress, neurodegeneration, and memory impairment in a mouse model of Alzheimer's disease, pp.Mol. Neurobiol, 2018[DOI]
  17. Song Y, "Effects of blueberry anthocyanins on retinal oxidative stress and inflammation in diabetes through Nrf2", HO-1 signaling, 2016, pp.301, 1~6
  18. Shaw P, "Nrf2-ARE signaling in cellular protection : mechanism of action and the regulatory mechanisms", J. Cell. Physiol, 235, pp.3119~3130 (2020)
  19. Jenkins T, "Nrf2 in cancer, detoxifying enzymes and cell death programs", Antioxidants(Basel), 10, pp.1030~ (2021)
  20. Yu ZY, "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, pp.28~42 (2018)
  21. Peng W, "Cyanidin-3-glucoside improves the barrier function of retinal pigment epithelium cells by attenuating endoplasmic reticulum stress-induced apoptosis", Food Res. Int, 157, pp.111313~ (2022)
  22. Ni T, "Protective effects of delphinidin against H2O2-induced oxidative injuries in human retinal pigment epithelial cells", Biosci. Rep, 39, pp.BSR20190689~ (2019)
  23. Park C, "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, pp.3030~ (2021)
  24. Han MH, "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, pp.13~21 (2018)
  25. Lu JN, "The inhibitory effect of anthocyanins on Akt on invasion and epithelialmesenchymal transition is not associated with the anti-EGFR effect of the anthocyanins", Int. J. Oncol, 44, pp.1756~1766 (2014)
  26. Yun JW, "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, pp.903~909 (2010)
  27. Shin DY, "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, pp.1499~1504 (2009)
  28. Park C, "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, pp.927898~ (2022)
  29. Jeong MJ, "Protection of oxidative stress-induced DNA damage and apoptosis by rosmarinic acid in murine myoblast C2C12 cells", Biotechnol. Bioprocess Eng, 27, pp.171~182 (2022)
  30. Mukherjee S, "Carboxylesterase3(Ces3)Interacts with bone morphogenetic protein 11 and promotes differentiation of osteoblasts via Smad1", 5, Biotechnol. Bioprocess Eng, pp.2022, 27[DOI]
  31. Choi YH, "Tacrolimus induces apoptosis in leukemia Jurkat cells through inactivation of the reactive oxygen species-dependent phosphoinositide-3-kinase", Akt signaling pathway, 2022, pp.27, 183~192
  32. Sukjamnong S, "Fimbristylis ovata and Artemisia vulgaris extracts inhibited AGE-mediated RAGE expression, ROS generation, and inflammation in THP-1 cells", Toxicol. Res, 38, pp.331~343 (2022)
  33. Park C, "Protective effect of diphlorethohydroxycarmalol against oxidative stress-induced DNA damage and apoptosis in retinal pigment epithelial cells", Cutan. Ocul. Toxicol, 38, pp.298~308 (2019)
  34. Hernandez M, "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, pp.1423~ (2021)
  35. Mahendra CK, "Detrimental effects of UVB on retinal pigment epithelial cells and its role in age-related macular degeneration", Oxid. Med. Cell. Longev, 2020, pp.1904178~ (2020)
  36. Tong Y, "Role of mitochondria in retinal pigment epithelial aging and degeneration", Front. Aging, 3, pp.926627~ (2022)
  37. Cordelli E, "Comet assay : a versatile but complex tool in genotoxicity testing", Toxicol. Res. (Camb. ), 10, pp.68~78 (2021)
  38. Kopp B, "Validation of the γH2AX biomarker for genotoxicity assessment : a review", Arch. Toxicol, 93, pp.2103~2114 (2019)
  39. Hahm JY, "8-Oxoguanine : from oxidative damage to epigenetic and epitranscriptional modification", Exp. Mol. Med, 54, pp.1626~1642 (2022)
  40. Lou MF, "Glutathione and glutaredoxin in redox regulation and cell signaling of the lens", Antioxidants(Basel), 11, pp.1973~ (2022)
  41. Enns GM, "Glutathione as a redox biomarker in mitochondrial disease-implications for therapy", J. Clin. Med, 6, pp.50~ (2017)
  42. Wang Y, "The protective effects of berry-derived anthocyanins against visible light-induced damage in human retinal pigment epithelial cells", J. Sci. Food d Agric, 95, pp.936~944 (2015)
  43. Tiwari S, "Targeted antioxidant delivery modulates mitochondrial functions, ameliorates oxidative stress and preserve sperm quality during cryopreservation", Theriogenology, 179, pp.22~31 (2022)
  44. Bock FJ, "Mitochondria as multifaceted regulators of cell death", Nat. Rev. Mol. Cell Biol, 21, pp.85~100 (2020)
  45. Kiraz Y, "Major apoptotic mechanisms and genes involved in apoptosis", Tumor Biol, 37, pp.8471~8486 (2016)
  46. Clementi ME, "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, pp.503~ (2022)
  47. Dinc E, "Protective effect of combined caffeic acid phenethyl ester and bevacizumab against hydrogen peroxide-induced oxidative stress in human RPE cells", Curr. Eye Res, 42, pp.1659~1666 (2017)
  48. Lalier L, "Bcl-2 Family members and the mitochondrial import machineries : the roads to death", Biomolecules, 12, pp.162~ (2022)
  49. Du Y, "Phillyrin mitigates apoptosis and oxidative stress in hydrogen peroxide-treated RPE cells through activation of the Nrf2 signaling pathway", Oxid. Med. Cell. Longev, 2020, pp.2684672~ (2020)
  50. You L, "Catalpol protects ARPE-19 cells against oxidative stress via activation of the Keap1", Nrf2, Cells, pp.2021, 10[DOI]

관련 논문AI추천

BlingLife ® -Marigold Extract Alleviates Blue Light-Induced Retinal Mitochondria Oxidative Stress and Senescence by Activating NRF2/HO-1 SignalingLi Sizhen, Xie Kexin, Yang Qingsong, Zheng Pengjie, Zhou Zixiu한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2025 · 제35권 Fisetin Protects C2C12 Mouse Myoblasts from Oxidative Stress-Induced Cytotoxicity through Regulation of the Nrf2/HO-1 Signaling박철, 박신형, 정재훈, 홍수현, Bang EunJin, Cha Hee-Jae, Choi Yung Hyun, Kim Da Hye, Kim Gi-Young, Kwon Chan-Young한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2023 · 제33권 제5호방사선 돌연변이 블랙베리 주성분 Cyanidin-3-glucoside의과산화수소 유발 산화적 손상에 대한 세포 보호 효과소양강, 육홍선, 이창욱, 정일윤, 조병옥, 진창현(사)한국방사선산업학회 · 방사선산업학회지2014 · 제8권 제1호산화스트레스가 유도된 망막색소상피세포에서 폴리페놀 화합물이 보이는 세포보호 효과곽형우, 서경훈, 유승영대한안과학회 · 대한안과학회지2016 · 제57권 제1호Role of heme oxygenase-1 expression by dietary phytoconstituents: A nutritional cytoprotective strategy for human diseases이승은, Yong Seek Park셀메드 세포교정의약학회 · 셀메드2013 · 제3권 제1호Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1강지숙, 김정희, 김철홍, 송춘호, 윤현민, 이유환, 장경전, 최영현대한약침학회 · Journal of Pharmacopuncture2016 · 제19권 제1호

이 간행물의 다른 논문 (24건)