DOI QR코드

DOI QR Code

Protective effects of red orange (Citrus sinensis [L.] Osbeck [Rutaceae]) extract against UVA-B radiation-induced photoaging in Skh:HR-2 mice

  • Yoon Hee Kim (Technology Development Center, BTC Corporation) ;
  • Cho Young Lim (Technology Development Center, BTC Corporation) ;
  • Jae In Jung (Industry Coupled Cooperation Center for Bio Healthcare Materials, Hallym University) ;
  • Tae Young Kim (Technology Development Center, BTC Corporation) ;
  • Eun Ji Kim (Industry Coupled Cooperation Center for Bio Healthcare Materials, Hallym University)
  • Received : 2022.11.15
  • Accepted : 2023.01.30
  • Published : 2023.08.01

Abstract

BACKGROUND/OBJECTIVES: The skin is the outermost organ of the human body and plays a protective role against external environmental damages, such as sunlight and pollution, which affect anti-oxidant defenses and skin inflammation, resulting in erythema or skin reddening, immunosuppression, and epidermal DNA damage. MATERIALS/METHODS: The present study aimed to investigate the potential protective effects of red orange complex H extract (ROC) against ultraviolet (UV)-induced skin photoaging in Skh:HR-2 mice. ROC was orally administered at doses of 20, 40, and 80 mg/kg/day for 13 weeks, along with UV irradiation of the mice for 10 weeks. RESULTS: ROC improved UV-induced skin barrier parameters, including erythema, melanin production, transepidermal water loss, elasticity, and wrinkle formation. Notably, ROC inhibited the mRNA expression of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor α) and melanogenesis. In addition, ROC recovered the UV-induced decrease in the hyaluronic acid and collagen levels by enhancing genes expression. Furthermore, ROC significantly downregulated the protein and mRNA expression of matrix metalloproteinases responsible for collagen degradation. These protective effects of ROC against photoaging are associated with the suppression of UV-induced phosphorylation of c-Jun NH2-terminal kinase and activator protein 1 activation. CONCLUSIONS: Altogether, our findings suggest that the oral administration of ROC exerts potential protective activities against photoaging in UV-irradiated hairless mice.

Keywords

Acknowledgement

The authors would like to express their gratitude to Bionap S.r.l for providing the red orange standardized extract.

References

  1. Parrado C, Mercado-Saenz S, Perez-Davo A, Gilaberte Y, Gonzalez S, Juarranz A. Environmental stressors on skin aging. Mechanistic insights. Front Pharmacol 2019;10:759.
  2. Gilchrest BA, Yaar M. Ageing and photoageing of the skin: observations at the cellular and molecular level. Br J Dermatol 1992;127 Suppl 41:25-30. https://doi.org/10.1111/j.1365-2133.1992.tb16984.x
  3. Cavinato M, Waltenberger B, Baraldo G, Grade CVC, Stuppner H, Jansen-Durr P. Plant extracts and natural compounds used against UVB-induced photoaging. Biogerontology 2017;18:499-516. https://doi.org/10.1007/s10522-017-9715-7
  4. Chiang HM, Chen HC, Lin TJ, Shih IC, Wen KC. Michelia alba extract attenuates UVB-induced expression of matrix metalloproteinases via MAP kinase pathway in human dermal fibroblasts. Food Chem Toxicol 2012;50:4260-9. https://doi.org/10.1016/j.fct.2012.08.018
  5. Hwang E, Park SY, Lee HJ, Lee TY, Sun ZW, Yi TH. Gallic acid regulates skin photoaging in UVB-exposed fibroblast and hairless mice. Phytother Res 2014;28:1778-88. https://doi.org/10.1002/ptr.5198
  6. Gromkowska-Kepka KJ, Puscion-Jakubik A, Markiewicz-Zukowska R, Socha K. The impact of ultraviolet radiation on skin photoaging - review of in vitro studies. J Cosmet Dermatol 2021;20:3427-31. https://doi.org/10.1111/jocd.14033
  7. Matsumura Y, Ananthaswamy HN. Toxic effects of ultraviolet radiation on the skin. Toxicol Appl Pharmacol 2004;195:298-308. https://doi.org/10.1016/j.taap.2003.08.019
  8. Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol 2002;4:E131-6. https://doi.org/10.1038/ncb0502-e131
  9. Geoffrey K, Mwangi AN, Maru SM. Sunscreen products: rationale for use, formulation development and regulatory considerations. Saudi Pharm J 2019;27:1009-18. https://doi.org/10.1016/j.jsps.2019.08.003
  10. Parrado C, Philips N, Gilaberte Y, Juarranz A, Gonzalez S. Oral photoprotection: effective agents and potential candidates. Front Med (Lausanne) 2018;5:188.
  11. Cimino F, Cristani M, Saija A, Bonina FP, Virgili F. Protective effects of a red orange extract on UVB-induced damage in human keratinocytes. Biofactors 2007;30:129-38. https://doi.org/10.1002/biof.5520300206
  12. Saija A, Tomaino A, Lo Cascio R, Rapisarda P, Dederen JC. In vitro antioxidant activity and in vivo photoprotective effect of a red orange extract. Int J Cosmet Sci 1998;20:331-42. https://doi.org/10.1046/j.1467-2494.1998.177057.x
  13. Vitali F, Pennisi C, Tomaino A, Bonina F, De Pasquale A, Saija A, Tita B. Effect of a standardized extract of red orange juice on proliferation of human prostate cells in vitro. Fitoterapia 2006;77:151-5. https://doi.org/10.1016/j.fitote.2005.10.001
  14. Bonina FP, Puglia C, Frasca G, Cimino F, Trombetta D, Tringali G, Roccazzello A, Insiriello E, Rapisarda P, Saija A. Protective effects of a standardised red orange extract on air pollution-induced oxidative damage in traffic police officers. Nat Prod Res 2008;22:1544-51. https://doi.org/10.1080/14786410701740401
  15. Balestra C, Cimino F, Theunissen S, Snoeck T, Provyn S, Canali R, Bonina A, Virgili F. A red orange extract modulates the vascular response to a recreational dive: a pilot study on the effect of anthocyanins on the physiological consequences of scuba diving. Nat Prod Res 2016;30:2101-6. https://doi.org/10.1080/14786419.2015.1107062
  16. Tomasello B, Malfa GA, Acquaviva R, La Mantia A, Di Giacomo C. Phytocomplex of a standardized extract from red orange (Citrus sinensis L. Osbeck) against photoaging. Cells 2022;11:1447.
  17. Nobile V, Burioli A, Yu S, Zhifeng S, Cestone E, Insolia V, Zaccaria V, Malfa GA. Photoprotective and antiaging effects of a standardized red orange (Citrus sinensis (L.) Osbeck) extract in Asian and Caucasian subjects: a randomized, double-blind, controlled study. Nutrients 2022;14:2241.
  18. Peng LH, Liu S, Xu SY, Chen L, Shan YH, Wei W, Liang WQ, Gao JQ. Inhibitory effects of salidroside and paeonol on tyrosinase activity and melanin synthesis in mouse B16F10 melanoma cells and ultraviolet B-induced pigmentation in guinea pig skin. Phytomedicine 2013;20:1082-7.  https://doi.org/10.1016/j.phymed.2013.04.015
  19. Lee HS, Lim SM, Jung JI, Kim SM, Lee JK, Kim YH, Cha KM, Oh TK, Moon JM, Kim TY, et al. Gynostemma pentaphyllum extract ameliorates high-fat diet-induced obesity in C57BL/6N mice by upregulating SIRT1. Nutrients 2019;11:2475.
  20. Cho HJ, Kim WK, Kim EJ, Jung KC, Park S, Lee HS, Tyner AL, Park JH. Conjugated linoleic acid inhibits cell proliferation and ErbB3 signaling in HT-29 human colon cell line. Am J Physiol Gastrointest Liver Physiol 2003;284:G996-1005. https://doi.org/10.1152/ajpgi.00347.2002
  21. US Food and Drug Administration. Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. Rockville (MD): US Food and Drug Administration; 2005. 
  22. Yoshizumi M, Nakamura T, Kato M, Ishioka T, Kozawa K, Wakamatsu K, Kimura H. Release of cytokines/chemokines and cell death in UVB-irradiated human keratinocytes, HaCaT. Cell Biol Int 2008;32:1405-11. https://doi.org/10.1016/j.cellbi.2008.08.011
  23. Duan X, Wu T, Liu T, Yang H, Ding X, Chen Y, Mu Y. Vicenin-2 ameliorates oxidative damage and photoaging via modulation of MAPKs and MMPs signaling in UVB radiation exposed human skin cells. J Photochem Photobiol B 2019;190:76-85. https://doi.org/10.1016/j.jphotobiol.2018.11.018
  24. Pittayapruek P, Meephansan J, Prapapan O, Komine M, Ohtsuki M. Role of matrix metalloproteinases in photoaging and photocarcinogenesis. Int J Mol Sci 2016;17:868.
  25. Choi SI, Jung TD, Cho BY, Choi SH, Sim WS, Han X, Lee SJ, Kim YC, Lee OH. Anti-photoaging effect of fermented agricultural by-products on ultraviolet B-irradiated hairless mouse skin. Int J Mol Med 2019;44:559-68. https://doi.org/10.3892/ijmm.2019.4242
  26. Young AR. Acute effects of UVR on human eyes and skin. Prog Biophys Mol Biol 2006;92:80-5. https://doi.org/10.1016/j.pbiomolbio.2006.02.005
  27. Saewan N, Jimtaisong A. Natural products as photoprotection. J Cosmet Dermatol 2015;14:47-63. https://doi.org/10.1111/jocd.12123
  28. Yadav T, Mishra S, Das S, Aggarwal S, Rani V. Anticedants and natural prevention of environmental toxicants induced accelerated aging of skin. Environ Toxicol Pharmacol 2015;39:384-91. https://doi.org/10.1016/j.etap.2014.11.003
  29. Grosso G, Galvano F, Mistretta A, Marventano S, Nolfo F, Calabrese G, Buscemi S, Drago F, Veronesi U, Scuderi A. Red orange: experimental models and epidemiological evidence of its benefits on human health. Oxid Med Cell Longev 2013;2013:157240.
  30. de Lima LP, de Paula BA. A review of the lipolytic effects and the reduction of abdominal fat from bioactive compounds and Moro orange extracts. Heliyon 2021;7:e07695.
  31. Ribeiro AP, Pereira AG, Todo MC, Fujimori AS, Dos Santos PP, Dantas D, Fernandes AA, Zanati SG, Hassimotto NM, Zornoff LA, et al. Pera orange (Citrus sinensis) and Moro orange (Citrus sinensis (L.) Osbeck) juices attenuate left ventricular dysfunction and oxidative stress and improve myocardial energy metabolism in acute doxorubicin-induced cardiotoxicity in rats. Nutrition 2021;91-92:111350.
  32. Buscemi S, Rosafio G, Arcoleo G, Mattina A, Canino B, Montana M, Verga S, Rini G. Effects of red orange juice intake on endothelial function and inflammatory markers in adult subjects with increased cardiovascular risk. Am J Clin Nutr 2012;95:1089-95. https://doi.org/10.3945/ajcn.111.031088
  33. Magalhaes ML, de Sousa RV, Miranda JR, Konig IF, Wouters F, Souza FR, Simao SD, da Silva LA, Nelson DL, das Gracas CM. Effects of Moro orange juice (Citrus sinensis (L.) Osbeck) on some metabolic and morphological parameters in obese and diabetic rats. J Sci Food Agric 2021;101:1053-64. https://doi.org/10.1002/jsfa.10714
  34. Jiang SJ, Chu AW, Lu ZF, Pan MH, Che DF, Zhou XJ. Ultraviolet B-induced alterations of the skin barrier and epidermal calcium gradient. Exp Dermatol 2007;16:985-92. https://doi.org/10.1111/j.1600-0625.2007.00619.x
  35. Haratake A, Uchida Y, Schmuth M, Tanno O, Yasuda R, Epstein JH, Elias PM, Holleran WM. UVB-induced alterations in permeability barrier function: roles for epidermal hyperproliferation and thymocyte-mediated response. J Invest Dermatol 1997;108:769-75.  https://doi.org/10.1111/1523-1747.ep12292163
  36. Mojumdar EH, Pham QD, Topgaard D, Sparr E. Skin hydration: interplay between molecular dynamics, structure and water uptake in the stratum corneum. Sci Rep 2017;7:15712.
  37. Dai G, Freudenberger T, Zipper P, Melchior A, Grether-Beck S, Rabausch B, de Groot J, Twarock S, Hanenberg H, Homey B, et al. Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases. Am J Pathol 2007;171:1451-61. https://doi.org/10.2353/ajpath.2007.070136
  38. Yun MS, Kim C, Hwang JK. Agastache rugosa Kuntze attenuates UVB-induced photoaging in hairless mice through the regulation of MAPK/AP-1 and TGF-β/Smad pathways. J Microbiol Biotechnol 2019;29:1349-60. https://doi.org/10.4014/jmb.1908.08020
  39. Razia S, Park H, Shin E, Shim KS, Cho E, Kim SY. Effects of Aloe vera flower extract and its active constituent isoorientin on skin moisturization via regulating involucrin expression: in vitro and molecular docking studies. Molecules 2021;26:2626.
  40. Lee HJ, Im AR, Kim SM, Kang HS, Lee JD, Chae S. The flavonoid hesperidin exerts anti-photoaging effect by downregulating matrix metalloproteinase (MMP)-9 expression via mitogen activated protein kinase (MAPK)-dependent signaling pathways. BMC Complement Altern Med 2018;18:39.
  41. Park JE, Pyun HB, Woo SW, Jeong JH, Hwang JK. The protective effect of Kaempferia parviflora extract on UVB-induced skin photoaging in hairless mice. Photodermatol Photoimmunol Photomed 2014;30:237-45. https://doi.org/10.1111/phpp.12097
  42. Han HS, Shin JS, Myung DB, Ahn HS, Lee SH, Kim HJ, Lee KT. Hydrangea serrata (Thunb.) Ser. extract attenuate UVB-induced photoaging through MAPK/AP-1 inactivation in human skin fibroblasts and hairless mice. Nutrients 2019;11:553.