Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Hesperidin Attenuates Ultraviolet B-Induced Apoptosis by Mitigating Oxidative Stress in Human Keratinocytes

  • Hewage, Susara Ruwan Kumara Madduma (School of Medicine, Jeju National University) ;
  • Piao, Mei Jing (School of Medicine, Jeju National University) ;
  • Kang, Kyoung Ah (School of Medicine, Jeju National University) ;
  • Ryu, Yea Seong (School of Medicine, Jeju National University) ;
  • Han, Xia (School of Medicine, Jeju National University) ;
  • Oh, Min Chang (School of Medicine, Jeju National University) ;
  • Jung, Uhee (Radiation Biotechnology Research Division, Korea Atomic Energy Research Institute) ;
  • Kim, In Gyu (Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute) ;
  • Hyun, Jin Won (School of Medicine, Jeju National University)
  • Received : 2015.08.31
  • Accepted : 2015.10.26
  • Published : 2016.05.01
Download PDF
⟨ Previous Next ⟩

Abstract

Human skin cells undergo pathophysiological processes via generation of reactive oxygen species (ROS) upon excessive exposure to ultraviolet B (UVB) radiation. This study investigated the ability of hesperidin ($C_{28}H_{34}O_{15}$) to prevent apoptosis due to oxidative stress generated through UVB-induced ROS. Hesperidin significantly scavenged ROS generated by UVB radiation, attenuated the oxidation of cellular macromolecules, established mitochondrial membrane polarization, and prevented the release of cytochrome c into the cytosol. Hesperidin downregulated expression of caspase-9, caspase-3, and Bcl-2-associated X protein, and upregulated expression of B-cell lymphoma 2. Hesperidin absorbed wavelengths of light within the UVB range. In summary, hesperidin shielded human keratinocytes from UVB radiation-induced damage and apoptosis via its antioxidant and UVB absorption properties.

Keywords

References

  1. Adrain, C. and Martin, S. J. (2001) The mitochondrial apoptosome: A killer unleashed by the cytochrome seas. Trends Biochem. Sci. 26, 390-397. https://doi.org/10.1016/S0968-0004(01)01844-8
  2. Amado, N. G., Cerqueira, D. M. and Menezes, F. S. (2009) Isoquercitrin isolated from Hyptis fasciculata reduces glioblastoma cell proliferation and changes beta-catenin cellular localization. Anticancer Drugs 20, 543-552. https://doi.org/10.1097/CAD.0b013e32832d1149
  3. Antonsson, B., Conti, F., Ciavatta, A., Montessuit, S., Lewis, S., Martinou, I., Bernasconi, L., Bernard, A., Mermod, J. J., Mazzei, G., Maundrell, K., Gambale, F., Sadoul, R. and Martinou, J. C. (1997) Inhibition of Bax channel-forming activity by Bcl-2. Science 277, 370-372. https://doi.org/10.1126/science.277.5324.370
  4. Arends, M. J., Morris, R. G. and Wyllie, A. H. (1990) Apoptosis. The role of the endonuclease. Am. J. Pathol. 136, 593-608.
  5. Bartoszewski, R., Hering, A., Marszall, M., Stefanowicz Hajduk, J., Bartoszewska, S., Kapoor, N., Kochan, K. and Ochocka, R. (2014) Mangiferin has an additive effect on the apoptotic properties of hesperidin in Cyclopia sp. tea extracts. PLoS One. 3, e92128.
  6. Beauchamp, M. C., Letendre, E. and Renier, G. (2002) Macrophage lipoprotein lipase expression is increased in patients with heterozygous familial hypercholesterolemia. J. Lipid Res. 43, 215-222.
  7. Belli, R., Amerio, P., Brunetti, L., Orlando, G., Toto, P., Proietto, G., Vacca, M. and Tulli, A. (2005) Elevated 8-isoprostane levels in basal cell carcinoma and in UVA irradiated skin. Int. J. Immunopathol. Pharmacol. 18, 497-502. https://doi.org/10.1177/039463200501800309
  8. Black, H. S., de Gruijl, F. R., Forbes, P. D., Cleaver, J. E., Ananthaswamy, H. N., de Fabo, E. C., Ullrich, S. E. and Tyrrell, R. M. (1997) Photocarcinogenesis: an overview. J. Photochem. Photobiol. B 40, 29-47. https://doi.org/10.1016/S1011-1344(97)00021-3
  9. Bolaji, B. and Huan, Z. (2013) Ozone depletion and global warming: Case for the use of natural refrigerant-a review. Renew. Sustain. Energy Rev. 18, 49-54. https://doi.org/10.1016/j.rser.2012.10.008
  10. Caldwell, M. M., Bornman, J. F., Ballare, C. L., Flint, S. D. and Kulandaivelu, G. (2007) Terrestrial ecosystems, increased solar ultraviolet radiation and interactions with other climate change factors. Photochem. Photobiol. Sci. 6, 252-266. https://doi.org/10.1039/b700019g
  11. Campanini, M. Z., Pinho-Ribeiro, F. A., Ivan, A. L., Ferreira, V. S., Vilela, F. M., Vicentini, F. T., Martinez, R. M., Zarpelon, A. C., Fonseca, M. J., Faria, T. J., Baracat, M. M., Verri, W. A., Georgetti, S. R. and Casagrande, R. (2013) Efficacy of topical formulations containing Pimenta pseudocaryophyllusextract against UVB-induced oxidative stress and inflammation in hairless mice. J. Photochem. Photobiol. B 127, 153-160. https://doi.org/10.1016/j.jphotobiol.2013.08.007
  12. Chiba, H., Uehara, M., Wu, J., Wang, X., Masuyama, R., Suzuki, K., Kanazawa, K. and Ishimi, Y. (2003) Hesperidin, a citrus flavonoid, inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice. J. Nutr. 133, 1892-1897. https://doi.org/10.1093/jn/133.6.1892
  13. Cross, C. E., Halliwell, B., Borish, E. T., Pryor, W. A., Ames, B. N., Saul, R .L., McCord, J. M. and Harman, D. (1987) Oxygen radicals and human disease. Ann. Intern. Med. 107, 526-545. https://doi.org/10.7326/0003-4819-107-4-526
  14. Dalle-Donne, I., Rossi, R., Giustarini, D., Milzani, A. and Colombo, R. (2003) Protein carbonyl groups as biomarkers of oxidative stress. Clin. Chim. Acta 329, 23-38. https://doi.org/10.1016/S0009-8981(03)00003-2
  15. Dhumrongvaraporn, A. and Chanvorachote, P. (2013) Kinetics of ultraviolet B irradiation-mediated reactive oxygen species generation in human keratinocytes. J. Cosmet. Sci. 64, 207-217.
  16. Drouin, R. and Therrien, J. P. (1997) UVB-induced cyclobutane pyrimidine dimer frequency correlates with skin cancer mutational hotspots in p53. Photochem. Photobiol. 66, 719-726. https://doi.org/10.1111/j.1751-1097.1997.tb03213.x
  17. Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A. and Nagata, S. (1998) A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 391, 43-50. https://doi.org/10.1038/34112
  18. Gilchrest, B. A. and Yaar, M. (1992) Ageing and photoageing of the skin: observations at the cellular and molecular level. Br. J. Dermatol. 127, 25-30. https://doi.org/10.1111/j.1365-2133.1992.tb16984.x
  19. Karol, M. H. (2009) How environmental agents influence the aging process. Biomol. Ther. (Seoul) 17, 113-124. https://doi.org/10.4062/biomolther.2009.17.2.113
  20. Levine, R. L., Garland, D., Oliver, C. N., Amici, A., Climent, I., Lenz, A. G., Ahn, B. W., Shaltiel, S. and Stadtman, E. R. (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 186, 464-478. https://doi.org/10.1016/0076-6879(90)86141-H
  21. Li, L, Abe, Y., Mashino, T., Mochizuki, M. and Miyata, N. (2003) Signal enhancement in ESR spin-trapping for hydroxyl radicals. Anal. Sci. 19, 1083-1084. https://doi.org/10.2116/analsci.19.1083
  22. Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S. and Wang, X. (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-489. https://doi.org/10.1016/S0092-8674(00)80434-1
  23. Mabruk, M. J., Toh, L. K., Murphy, M., Leader, M., Kay, E. and Murphy, G. M. (2009) Investigation of the effect of UV irradiation on DNA damage: comparison between skin cancer patients and normal volunteers. J. Cutan. Pathol. 36, 760-765. https://doi.org/10.1111/j.1600-0560.2008.01164.x
  24. Maurya, A. K. and Vinayak, M. (2015) Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line. Mol. Biol. Rep. 42, 1419-1429. https://doi.org/10.1007/s11033-015-3921-7
  25. McKenzie, R. L., Aucamp, P. J., Bais, A. F., Bjorn, L. O., Ilyas, M. and Madronich, S. (2011) Ozone depletion and climate change: impacts on UV radiation. Photochem. Photobiol. Sci. 10, 182-198. https://doi.org/10.1039/c0pp90034f
  26. Ohtsuki, K., Abe, A., Mitsuzumi, H., Kondo, M., Uemura, K., Iwasaki, Y. and Kondo, Y. (2003). Glucosyl hesperidin improves serum cholesterol composition and inhibits hypertrophy in vasculature. J. Nutr. Sci. Vitaminol. 49, 447-450. https://doi.org/10.3177/jnsv.49.447
  27. Ravanat, J. L., Douki, T. and Cadet, J. (2001) Direct and indirect effects of UV radiation on DNA and its components. J. Photochem. Photobiol. B 63, 88-102. https://doi.org/10.1016/S1011-1344(01)00206-8
  28. Rosenkranz, A. R., Schmaldienst, S., Stuhlmeier, K. M., Chen, W., Knapp, W. and Zlabinger, G. J. (1992) A microplate assay for the detection of oxidative products using 2',7' dichlorofluorescin-diacetate. J. Immunol. Methods 156, 39-45. https://doi.org/10.1016/0022-1759(92)90008-H
  29. Saiprasad, G., Chitra, P., Manikandan, R. and Sudhandiran, G. (2014) Hesperidin induces apoptosis and triggers autophagic markers through inhibition of Aurora-A mediated phosphoinositide-3-kinase/ Akt/mammalian target of rapamycin and glycogen synthase kinase- 3 beta signalling cascades in experimental colon carcinogenesis. Eur. J. Cancer 50, 2489-2507. https://doi.org/10.1016/j.ejca.2014.06.013
  30. Shindo, Y., Witt, E., Han, D., Epstein, W. and Packer, L. (1994) Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin. J. Invest. Dermatol. 102, 122-124. https://doi.org/10.1111/1523-1747.ep12371744
  31. Singh, N. P. (2000) Microgels for estimation of DNA strand breaks, DNA protein crosslinks and apoptosis. Mutat. Res. 455, 111-127. https://doi.org/10.1016/S0027-5107(00)00075-0
  32. Slee, E. A., Harte, M. T., Kluck, R. M., Wolf, B. B., Casiano, C. A., Newmeyer, D. D., Wang, H. G., Reed, J. C., Nicholson, D. W., Alnemri, E. S., Green, D. R. and Martin, S. J. (1999) Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J. Cell Biol. 144, 281-292. https://doi.org/10.1083/jcb.144.2.281
  33. Svobodova, A. R., Galandakova, A., Sianska, J., Dolezal, D., Lichnovska, R., Ulrichova, J. and Vostalova, J. (2012) DNA damage after acute exposure of mice skin to physiological doses of UVB and UVA light. Arch. Dermatol. Res. 304, 407-412. https://doi.org/10.1007/s00403-012-1212-x
  34. Troiano, L., Ferraresi, R., Lugli, E., Nemes, E., Roat, E., Nasi, M., Pinti, M. and Cossarizza, A. (2007) Multiparametric analysis of cells with different mitochondrial membrane potential during apoptosis by polychromatic flow cytometry. Nat. Protoc. 2, 2719-2727. https://doi.org/10.1038/nprot.2007.405
  35. Turrens, J. F. (2003) Mitochondrial formation of reactive oxygen species. J. Physiol. 552, 335-344. https://doi.org/10.1113/jphysiol.2003.049478
  36. Waster, P. K. and Ollinger, K. M. (2009) Redox-dependent translocation of p53 to mitochondria or nucleus in human melanocytes after UVA- and UVB-induced apoptosis. J. Invest. Dermatol. 129, 1769-1781. https://doi.org/10.1038/jid.2008.421
  37. Wilson, K. P., Black, J. A., Thomson, J. A., Kim, E. E., Griffith, J. P., Navia, M. A., Murcko, M. A., Chambers, S. P., Aldape, R. A., Raybuck, S. A. and David, J. L. (1994) Structure and mechanism of interleukin-1 beta converting enzyme. Nature 370, 270-275. https://doi.org/10.1038/370270a0
  38. Zhang, R., Humphreys, I., Sahu, R. P., Shi, Y. and Srivastava, S. K. (2008) In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis 12, 1465-1478.

Cited by

  1. Hesperidin, a citrus bioflavonoid, alleviates trichloroethylene-induced oxidative stress in Drosophila melanogaster vol.55, 2017, https://doi.org/10.1016/j.etap.2017.08.038
  2. Exposure to Zinc Oxide Nanoparticles Induces Neurotoxicity and Proinflammatory Response: Amelioration by Hesperidin vol.175, pp.2, 2017, https://doi.org/10.1007/s12011-016-0770-8
  3. Protective Effects of Hesperidin (Citrus Flavonone) on High Glucose Induced Oxidative Stress and Apoptosis in a Cellular Model for Diabetic Retinopathy vol.9, pp.12, 2017, https://doi.org/10.3390/nu9121312
  4. The flavonoid hesperidin exerts anti-photoaging effect by downregulating matrix metalloproteinase (MMP)-9 expression via mitogen activated protein kinase (MAPK)-dependent signaling pathways vol.18, pp.1, 2018, https://doi.org/10.1186/s12906-017-2058-8
  5. Anti-inflammatory and antiradical effects of a 2% diosmin cream in a human skin organ culture as model vol.17, pp.5, 2018, https://doi.org/10.1111/jocd.12778
  6. Hesperidin alleviates zinc oxide nanoparticle induced hepatotoxicity and oxidative stress vol.19, pp.1, 2018, https://doi.org/10.1186/s40360-018-0256-8
  7. Suppression of Hepatitis C Virus Genome Replication and Particle Production by a Novel Diacylglycerol Acyltransferases Inhibitor vol.23, pp.8, 2018, https://doi.org/10.3390/molecules23082083
  8. bark extract and its active constituent hesperidin vol.32, pp.8, 2018, https://doi.org/10.1002/ptr.6092
  9. Antidepressant Flavonoids and Their Relationship with Oxidative Stress vol.2017, pp.None, 2016, https://doi.org/10.1155/2017/5762172
  10. Benefits of Hesperidin for Cutaneous Functions vol.2019, pp.None, 2016, https://doi.org/10.1155/2019/2676307
  11. Ultraviolet A protective potential of plant extracts and phytochemicals vol.164, pp.1, 2016, https://doi.org/10.5507/bp.2020.010
  12. Nutritional Profile and Health Benefits of Kinnow: An Updated Review vol.20, pp.suppl3, 2016, https://doi.org/10.1080/15538362.2020.1792390
  13. Hesperidin Loaded on Gold Nanoparticles as a Drug Delivery System for a Successful Biocompatible, Anti-Cancer, Anti-Inflammatory and Phagocytosis Inducer Model vol.10, pp.None, 2016, https://doi.org/10.1038/s41598-020-66419-6