Mechanisms of antioxidants in the treatment of vitiligo in vivo: a systematic review
DOI:
https://doi.org/10.33448/rsd-v11i16.38060Keywords:
Vitiligo; Antioxidants; Molecular mechanisms of pharmacological action; Biological assay; Systematic review.Abstract
Vitiligo is characterized by skin discoloration in different body regions, and its prevalence in the world population can reach 1%. Its cause is still undefined but possibly related to biochemical, environmental, immunological, and genetic events. In addition, individuals with vitiligo present electrolyte disturbances in the melanocytes, and it has been one of the targets of studies for treating this pathology. This systematic review aimed to gather and evaluate in vivo studies that described the mechanism of action of antioxidants in vitiligo. PubMed, Web of Science, Embase, Science Direct, LILACS, Open Grey and Google Scholar were used as research sources. The search included all articles up to October 16, 2021, with no start date restrictions. The search yielded 390 articles, and 7 of these were selected according to the inclusion criteria. The compounds studied in the articles selected for this review were curcumin, Cold Atmospheric Plasma, butin, galangin, 2',3,4,4'-tetrahydrochalcone and its derivatives, 6-benzylaminopurine, piperine, chrysin, kaempferol, scopoletin, vitamin D3, caffeic acid, and luteolin. The results showed that the main mechanisms of action of antioxidants in the treatment of vitiligo are the increase in tyrosinase activity by increasing the synthesis of TYR and TRP-1, the positive regulation of the number of epidermal cells, the redox balance, activation and regulation of MITF, and malondialdehyde and cholinesterase/acetylcholinesterase content. Thus, these pathways can be considered targets for evaluating different antioxidant compounds to act in treating vitiligo.
References
Abuduaini, A., Lu, X., Zang, D., Wu, T., & Aisa, H. A. (2021). Effects of a Traditional Caraway Formulation on Experimental Models of Vitiligo and Mechanisms of Melanogenesis. Evidence-Based Complementary and Alternative Medicine, 2021, 1-17. doi:10.1155/2021/6675657
Arican, O., & Kurutas, E. B. (2008). Oxidative stress in the blood of patients with active localized vitiligo. Acta Dermatovenerologica Alpina, Pannonica et Adriatica, 17(1), 12–16. Retrieved from http://s3-eu-west-1.amazonaws.com/thejournalhub/10.15570/archive/acta-apa-08-1/2.pdf
Bergqvist, C., & Ezzedine, K. (2020). Vitiligo: A Review. Dermatology, 236 (6), 1–22. doi: 10.1159/000506103
Brasil (2012). Ministério da Saúde. Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Departamento de Ciência e Tecnologia. Diretrizes metodológicas: elaboração de revisão sistemática e metanálise de ensaios clínicos randomizados. Brasília: Editora do Ministério da Saúde. 92 p. ISBN 978-85-334-1951-3
Cordero, R. J. B., & Casadevall, A. (1997). Melanin. Current Biology, 30(4), 142–143. doi: 10.1016/j.cub.2019.12.042
Daniel, B. S., & Wittal, R. (2015). Vitiligo treatment update. Australasian Journal of Dermatology, 56(2), 85–92. doi:10.1111/ajd.12256
De Luca Canto. (2020) Revisões sistemáticas da literatura: guia prático. 1.ed., Curitiba: Brazil Publishing. ISBN 978-65-5016-352-5
Ding, Q., Luo, L., Yu, L., Huang, S. lu, Wang, X. qin, & Zhang, B. (2021). The critical role of glutathione redox homeostasis towards oxidation in ermanin-induced melanogenesis. Free Radical Biology and Medicine, 176(8), 392–405. doi:10.1016/j.freeradbiomed.2021.09.017
Ezzedine, K., Eleftheriadou, V., Whitton, M., & Van Geel, N. (2015). Vitiligo. The Lancet, 386(9988), 74–84. doi:10.1016/S0140-6736(14)60763-7
Glassman, S. J. (2011). Vitiligo, reactive oxygen species and T-cells. Clinical Science, 120(3), 99–120. doi:10.1042/CS20090603
Gonzalez, G. A., & Montminy, M. R. (1989). Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell, 59(4), 675–680. doi:10.1016/0092-8674(89)90013-5
Gowda, V. K., Srinivas, S., & Srinivasan, V. M. (2020). Waardenburg Syndrome Type I. Indian Journal of Pediatrics, 87(3), 244. doi:10.1007/s12098-019-03170-5
Guerra, L., Dellambra, E., Brescia, S., & Raskovic, D. (2010). Vitiligo: Pathogenetic Hypotheses and Targets for Current Therapies. Current Drug Metabolism, 11(5), 451–467. doi:10.2174/138920010791526105
Guo, S., & Zhang, Q. (2021). Paeonol protects melanocytes against hydrogen peroxide-induced oxidative stress through activation of Nrf2 signaling pathway. Drug Development Research, 82(6), 861–869. doi:10.1002/ddr.21793
Heriniaina, R. M., Jing, D., & Kalavagunta, P. K. (2018). Effects of six compounds with different chemical structures on melanogenesis. 16(81874331), 766–773. doi:10.1016/S1875-5364(18)30116-X
Hooijmans, C. R., Rovers, M. M., De Vries, R. B. M., Leenaars, M., Ritskes-Hoitinga, M., & Langendam, M. W. (2014). SYRCLE’s risk of bias tool for animal studies. BMC Medical Research Methodology, 14(1), 1–9. doi:10.1186/1471-2288-14-43
Huo, S. X., Gao, L., Peng, X. M., Zhao, P. P., He, Y., & Yan, M. (2014). The Effects of Galangin on a Mouse Model of Vitiligo Induced by Hydroquinone. Chinese Traditional and Herbal Drugs, 45(16), 2358–2363. doi:10.1002/ptr.5161
Huo, S. X., Wang, Q., Liu, X. M., Ge, C. H., Gao, L., Peng, X. M., & Yan
, M. (2017). The Effect of Butin on the Vitiligo Mouse Model Induced by Hydroquinone. Phytotherapy Research, 31(5), 740–746. doi:10.1002/ptr.5794
Hwang, Y. S., Oh, S. W., Park, S. H., Lee, J., Yoo, J. A., Kwon, K., Park, S. J., Kim, J., Yu, E., Cho, J. Y., & Lee, J. (2019). Melanogenic effects of maclurin are mediated through the activation of cAMP/PKA/CREB and p38 MAPK/CREB signaling pathways. Oxidative Medicine and Cellular Longevity, 2019, 1–12. doi:10.1155/2019/9827519
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999). Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes and Development, 13(1), 76–86. doi: 10.1101/gad.13.1.76
Jung, H. M., Jung, Y. S., Lee, J. H., Kim, G. M., & Bae, J. M. (2018). Antioxidant supplements in combination with phototherapy for vitiligo: A systematic review and metaanalysis of randomized controlled trials. Journal of the American Academy of Dermatology, 85(2), 506–508. doi:10.1016/j.jaad.2018.10.010.
Karagaiah, P., Valle, Y., Sigova, J., Zerbinati, N., Vojvodic, P., Parsad, D., Schwartz, R. A., Grabbe, S., Goldust, M., & Lotti, T. (2020). Emerging drugs for the treatment of vitiligo. Expert Opinion on Emerging Drugs, 25(1), 7–24. doi:10.1080/14728214.2020.1712358
Kemp, E. H., Waterman, E. A., & Weetman, A. P. (2001). Autoimmune aspects of vitiligo. Autoimmunity, 34(1), 65–77. 10.3109/08916930108994127
Kim, H. J., Kim, J. S., Woo, J. T., Lee, I. S., & Cha, B. Y. (2015). Hyperpigmentation mechanism of methyl 3,5-di-caffeoylquinate through activation of p38 and MITF induction of tyrosinase. Acta Biochimica et Biophysica Sinica, 47(7), 548–556. doi:10.1093/abbs/gmv040
Lai, Y., Feng, Q., Zhang, R., Shang, J., & Zhong, H. (2021). The Great Capacity on Promoting Melanogenesis of Three Compatible Components in Vernonia anthelmintica ( L .) Willd . 22(8), 1-18. doi: 10.3390/ijms22084073
Macleod, M. R., O’Collins, T., Howells, D. W., & Donnan, G. A. (2004). Pooling of animal experimental data reveals influence of study design and publication bias. Stroke, 35(5), 1203–1208. doi:10.1161/01.STR.0000125719.25853.20
Mansourpour, H., Ziari, K., Kalantar Motamedi, S., & Hassan Poor, A. (2019). iNOS inhibition for vitiligo Therapeutic effects of iNOS inhibition against vitiligo in an animal model. Eur J Transl Myol, 29(3), 251–260. doi:10.4081/ejtm.2019.8383
Meneghin, R. A. (2021). Quali-quantitative synthesis of the global scenario of patent families about leprosy. Ciência & Saúde Coletiva, 26(11), 5411–5426. doi:10.1590/1413-812320212611.01452021
Nichols, J. A., & Katiyar, S. K. (2010). Skin photoprotection by natural polyphenols: Anti-inflammatory, antioxidant and DNA repair mechanisms. Archives of Dermatological Research, 302(2), 71–83. doi:10.1007/s00403-009-1001-3
Niture, S. K., Khatri, R., & Jaiswal, A. K. (2014). Regulation of Nrf2 - An update. Free Radical Biology and Medicine, 66, 36–44. doi:10.1016/j.freeradbiomed.2013.02.008
Niu, C., & Aisa, H. A. (2017). Upregulation of Melanogenesis and Tyrosinase Activity: Potential Agents for Vitiligo. Molecules, 22(8). doi:10.3390/molecules22081303
Niu, C., Yin, L., & Aisa, H. A. (2018). Novel furocoumarin derivatives stimulate melanogenesis in b16 melanoma cells by up-regulation of mitf and tyr family via Akt/GSK3β/β-catenin signaling pathways. International Journal of Molecular Sciences, 19(3). doi:10.3390/ijms19030746
Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., Chou, R., Glanville, J., Grimshaw, J. M., Hróbjartsson, A., Lalu, M. M., Li, T., Loder, E. W., Mayo-Wilson, E., McDonald, S., … Moher, D. (2021). Declaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas. Revista Española de Cardiología, 74(9), 790–799. doi: 10.1016/j.rec.2021.07.010
Picardo, M., Dell’Anna, M. L., Ezzedine, K., Hamzavi, I., Harris, J. E., Parsad, D., & Taieb, A. (2015). Vitiligo. Nature Reviews Disease Primers, 1. 1-16. doi:10.1038/nrdp.2015.11
Pillaiyar, T., Manickam, M., & Jung, S. H. (2017). Downregulation of melanogenesis: drug discovery and therapeutic options. Drug Discovery Today, 22(2), 282–298. doi:10.1016/j.drudis.2016.09.016
Pizzinat, N., Copin, N., Vindis, C., Parini, A., & Cambon, C. (1999). Reactive oxygen species production by monoamine oxidases in intact cells. Naunyn-Schmiedeberg’s Archives of Pharmacology, 359(5), 428–431. doi:10.1007/pl00005371
Rashighi, M., & Harris, J. E. (2017). Vitiligo Pathogenesis and Emerging Treatments. Dermatologic Clinics, 35(2), 257–265. doi:10.1016/j.det.2016.11.014
Rawls, J. F., & Johnson, S. L. (2000). Zebrafish kit mutation reveals primary and secondary regulation of melanocyte development during fin stripe regeneration. Development, 127(17), 3715–3724. doi:10.1242/dev.127.17.3715
Rezaei, N., Gavalas, N. G., Weetman, A. P., & Kemp, E. H. (2007). Autoimmunity as an aetiological factor in vitiligo. Journal of the European Academy of Dermatology and Venereology, 21(7), 865–876. doi:10.1111/j.1468-3083.2007.02228.x
Rzepka, Z., Buszman, E., Beberok, A., & Wrześniok, D. (2016). From tyrosine to melanin: Signaling pathways and factors regulating melanogenesis. Postepy Higieny i Medycyny Doswiadczalnej, 70, 695–708. doi:10.5604/17322693.1208033
Salzes C, Abadie S, Seneschal J, Whitton M, Meurant JM, Jouary T, Ballanger F, Boralevi F, Taieb A, Taieb C, Ezzedine K.(2015). The Vitiligo Impact Patient Scale (VIPs): Development and Validation of a Vitiligo Burden Assessment Tool. 136(1), 52-8 doi:10.1038/JID.2015.398
Schallreuter, K. U., & Elwary, S. (2007). Hydrogen peroxide regulates the cholinergic signal in a concentration dependent manner. Life Sciences, 80(24–25), 2221–2226. doi:10.1016/j.lfs.2007.01.028
Schallreuter, K. U., Elwary, S. M. A., Gibbons, N. C. J., Rokos, H., & Wood, J. M. (2004). Activation/deactivation of acetylcholinesterase by H2O 2: More evidence for oxidative stress in vitiligo. Biochemical and Biophysical Research Communications, 315(2), 502–508. doi:10.1016/j.bbrc.2004.01.082
Schallreuter, K. U., Moore, J., Wood, J. M., Beazley, W. D., Gaze, D. C., Tobin, D. J., Marshall, H. S., Panske, A., Panzig, E., & Hibberts, N. A. (1999). In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase. Journal of Investigative Dermatology Symposium Proceedings, 4(1), 91–96. doi:10.1038/sj.jidsp.5640189
Seneschal, J., Boniface, K., D’Arino, A., & Picardo, M. (2021). An update on Vitiligo pathogenesis. Pigment Cell and Melanoma Research, 34(2), 236–243. doi:10.1111/pcmr.12949
Serre, C., Busuttil, V., & Botto, J. M. (2018). Intrinsic and extrinsic regulation of human skin melanogenesis and pigmentation. International Journal of Cosmetic Science, 40(4), 328–347. doi:10.1111/ics.12466
Speeckaert, R., Dugardin, J., Lambert, J., Lapeere, H., Verhaeghe, E., Speeckaert, M. M., & van Geel, N. (2018). Critical appraisal of the oxidative stress pathway in vitiligo: a systematic review and meta-analysis. Journal of the European Academy of Dermatology and Venereology, 32(7), 1089–1098. doi:10.1111/jdv.14792
Sun, M. C., Xu, X. L., Lou, X. F., & Du, Y. Z. (2020). Recent progress and future directions: The nano-drug delivery system for the treatment of vitiligo. International Journal of Nanomedicine, 15, 3267–3279. doi:10.2147/IJN.S245326
Tipton, K. F. (2018). 90 Years of Monoamine Oxidase: Some Progress and Some Confusion. Journal of Neural Transmission, 125(11), 1519-1551. doi:10.1007/s00702-018-1881-5
Turrens, J. F. (2003). Mitochondrial formation of reactive oxygen species. Journal of Physiology, 552(2), 335–344. doi:10.1113/jphysiol.2003.049478
Van Den Wijngaard, R., Wankowicz-Kalinska, A., Pals, S., Weening, J., & Das, P. (2001). Autoimmune melanocyte destruction in vitiligo. Laboratory Investigation, 81(8), 1061–1067. doi:10.1038/labinvest.3780318
Videira, I. F. D. S., Moura, D. F. L., & Magina, S. (2013). Mechanisms regulating melanogenesis*. Anais Brasileiros de Dermatologia, 88(1), 76–83. doi:10.1590/s0365-05962013000100009
Wang, Y., Li, S., & Li, C. (2019). Perspectives of new advances in the pathogenesis of vitiligo: From oxidative stress to autoimmunity. Medical Science Monitor, 25, 1017–1023. doi:10.12659/MSM.914898
Wu, L. C., Lin, Y. Y., Yang, S. Y., Weng, Y. T., & Tsai, Y. T. (2011). Antimelanogenic effect of c-phycocyanin through modulation of tyrosinase expression by upregulation of ERK and downregulation of p38 MAPK signaling pathways. Journal of Biomedical Science, 18(1), 1–11. doi:10.1186/1423-0127-18-74
Xia, J., Zeng, W., Xia, Y., Wang, B., Xu, D., Liu, D., Kong, M. G., & Dong, Y. (2019). Cold atmospheric plasma induces apoptosis of melanoma cells via Sestrin2-mediated nitric oxide synthase signaling. Journal of Biophotonics, 12(1), 1–20. doi:10.1002/jbio.201800046
Xie, H., Zhou, F., Liu, L., Zhu, G., Li, Q., Li, C., & Gao, T. (2016). Vitiligo: How do oxidative stress-induced autoantigens trigger autoimmunity? Journal of Dermatological Science, 81(1), 3–9. doi:10.1016/j.jdermsci.2015.09.003
Yildirim, M., Baysal, V., Inaloz, H. S., & Can, M. (2004). The role of oxidants and antioxidants in generalized vitiligo at tissue level. Journal of the European Academy of Dermatology and Venereology, 18(6), 683–686. doi:10.1111/j.1468-3083.2004.01080.x
Zang, D., Niu, C., & Aisa, H. A. (2019). Amine derivatives of furocoumarin induce melanogenesis by activating Akt/GSK-3β/ β-catenin signal pathway. Drug Design, Development and Therapy, 13, 623–632. doi:10.2147/DDDT.S180960
Zhai, S., Xu, M., Li, Q., Guo, K., Chen, H., & Kong, M. G. (2021). Successful Treatment of Vitiligo with Cold Atmospheric Plasma ‒ Activated Hydrogel. Journal of Investigative Dermatology, 141(11), 2710-2719. doi:10.1016/j.jid.2021.04.019
Zhang, J., Hu, W., Wang, P., Ding, Y., Wang, H., & Kang, X. (2022). Research Progress on Targeted Antioxidant Therapy and Vitiligo. Oxidative Medicine and Cellular Longevity, 2022, 1–9. doi:10.1155/2022/1821780
Zhong, H., Zhou, J., An, X., Hua, Y., Lai, Y., Zhang, R., Ahmad, O., Zhang, Y., & Shang, J. (2019). Natural product-based design, synthesis and biological evaluation of 2′,3,4,4′-tetrahydrochalcone analogues as antivitiligo agents. 87, 523–533. doi:10.1016/j.bioorg.2019.03.054
Zouboulis, C. C., & Makrantonaki, E. (2011). Clinical aspects and molecular diagnostics of skin aging. Clinics in Dermatology, 29(1), 3–14. doi:10.1016/j.clindermatol.2010.07.001
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