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Effect of botulinum toxin A on tyrosinase and melanin: A literature review

  • Liowina Adlin Hokky ,
  • Made Ratna Saraswati ,
  • Ni Putu Sriwidyani ,
  • I Gusti Ayu Artini ,
  • I Putu Eka Widyadharma ,
  • Ketut Kwartantaya Winaya ,

Abstract

Background: Melanogenesis is the process of forming melanin pigment initiated by the amino acid L-tyrosine; the main enzyme is tyrosinase. Tyrosinase acts as a catalyst for the hydroxylation reaction of L-tyrosine to L-DOPA and the oxidation of o-diphenol to dopaquinone. Under physiological conditions, the above process can be protective for the skin. However, if it occurs chronically and the melanogenesis process is uncontrolled, the above process can cause hyperpigmentation. One modality that is being researched for its usefulness in the world of anti-aging as anti-hyperpigmentation agent is botulinum toxin A.

Literature review: Botulinum toxin A can inhibit the release of acetylcholine in nerve cells. Melanocytes originate from ectodermal tissue such as nervous tissue; it is hypothesized that this modality can also influence melanosomes directly on keratinized cells to form cross-dendritic connections. This was proven by SH-SY5Y neuroblastoma cells which had increased levels of botulinum toxin A, but not human dermal fibroblast cells. Botulinum toxin A is also hypothesized to indirectly impact the melanogenesis process by inhibiting pro-inflammatory cytokines mediated by the interaction of melanocytes, keratinocytes, and fibroblasts. Inhibition of pro-inflammatory cytokine production inhibits the melanin biosynthesis process. This assumption was proven by a decrease in three pro-inflammatory cytokines such as basic fibroblast growth factor (bFGF), interleukin (IL)-1a, and prostaglandin E2 in keratinocytes

Conclusion: Intradermal injection of the botulinum toxin A has the potential to modulate tyrosinase enzyme and melanin synthesis. Botulinum toxin A can modulate melanin synthesis by directly inhibiting melanin synthesis in melanocytes and indirectly by modulating the interaction between melanocytes, keratinocytes, and fibroblasts.

Section

References

  1. Pangkahila W, Wong LP. Evidence-Based Anti-Aging Medicine Hormone Replacement Therapy. 2015;TLC Publication: 51.
  2. Pangkahila W. Anti-Aging Tetap Muda dan Sehat. 2019. Jakarta: Kompas Media Nusantara: 7-94.
  3. Chaudhary M, Khan A, Gupta M. Skin ageing: Pathophysiology and current market treatment approaches. Curr Aging Sci. 2020;13(1);22-30.
  4. Ganceviciene R, Liakou AI, Theodoridis A, Makrantonaki E, Zouboulis CC. Skin anti-aging strategies. Dermato-endocrinology. 2012;4(3):308-319.
  5. Gupta A, Avci P, Dai T, Huang Y-Y, Hamblin MR. Ultraviolet radiation in wound care: sterilization and stimulation. Adv Wound Care. 2013;2(8):422-437.
  6. Guan LL, Lim HW, Mohammad TF. Sunscreens and photoaging: A review of current literature. Am J Clin Dermatol. 2021;22(6):819-828.
  7. Costin GE, Hearing VJ. Human skin pigmentation: Melanocytes modulate skin color in response to stress. FASEB J. 2007;21:976-994.
  8. Kumari S, Thng STG, Verma NK, Gautam HK. Melanogenesis Inhibitors. Acta Derm Venereol. 2018;98(10):924-931.
  9. Cordero RJB, Casadevall A. Melanin. Curr Biol. 2020;30(4):R142-R143.
  10. Guo L, et al. Recent Advances and Progress on Melanin: From Source to Application. Int J Mol Sci. 2023;24(5):4360.
  11. Solano F. Photoprotection and skin pigmentation: Melanin-related molecules and some other new agents obtained from natural sources. Molecules. 2020;25(7):1537.
  12. Putri WE, Kurniawati Y, Djauhari T. Depigmenting Agent Melanotoksik Pada Pengobatan Melasma. Med Health Sci J. 2018;2(2).
  13. Videira IF, dos S, Moura DFL, Magina S. Mechanisms regulating melanogenesis. Anais Brasileiros Dermatologia. 2013;88:76-83.
  14. D’Mello SAN, Finlay GJ, Baguley BC, Askarian-Amiri ME. Signaling pathways in melanogenesis. Int J Mol Sci. 2016;17(7):1144.
  15. Suryaningsih BE. Melanogenesis and its associated signalings. Bali Med J. 2020;9(1):327-331.
  16. Vittorio S, Dank C, Ielo L. Heterocyclic Compounds as Synthetic Tyrosinase Inhibitors: Recent Advances. Int J Mol Sci. 2023;24(10):9097.
  17. Awad SS, Moftah NH, Rashed LA, Touni AA, Telep RAA. Evaluation of the effect of narrow band‐ultraviolet B on the expression of tyrosinase, TYRP‐1, and TYRP‐2 mRNA in vitiligo skin and their correlations with clinical improvement: a retrospective study. Dermatol Ther. 2021;34(1):e14649.
  18. Lai X, Wichers HJ, Soler-Lopez M, Dijkstra BW. Structure and function of human tyrosinase and tyrosinase‐related proteins. Chemistry. 2018;24(1):47-55.
  19. Kang HY, Lee JW, Papaccio F, Bellei B, Picardo M. Alterations of the pigmentation system in the aging process. Pigment Cell Melanoma Res. 2021;34(4):800-813.
  20. Kooltheat N, Tedasen A, Yamasaki K, Chatatikun M. Melanogenesis Inhibitory Activity, Chemical Components and Molecular Docking Studies of Prunus cerasoides Buch.-Ham. D. Don. Flowers. J Evid Based Integrative Med. 2023;28:2515690X231152928.
  21. Chen H-W, Chou Y-S, Young T-H, Cheng N-C. Inhibition of melanin synthesis and melanosome transfer by chitosan biomaterials. J Biomed Materials Res Part B. 2020;108(4):1239-1250.
  22. Choi H, Kim K, Han J, Choi H, Jin SH, Lee EK, et al. Kojic acid-induced IL-6 production in human keratinocytes plays a role in its anti-melanogenic activity in skin. J Dermatol Sci. 2012;66(3):207-215.
  23. Satooka H, Kubo I. Resveratrol as a kcat type inhibitor for tyrosinase: potentiated melanogenesis inhibitor. Bioorganic Med Chem. 2012;20(2):1090-1099.
  24. Kim DH, Kim SJ, Ullah S, Yun HW, Chun P, Moon HR. Design, synthesis, and antimelanogenic effects of (2-substituted phenyl-1, 3-dithiolan-4-yl) methanol derivatives. Drug Design Development Ther. 2017;827-836.
  25. Taraz M, Niknam S, Ehsani AH. Tranexamic acid in treatment of melasma: A comprehensive review of clinical studies. Dermatol Ther. 2017;30(3):e12465.
  26. Nakao S, Nakagawa A, Oguchi Y, Mitsuda D, Kato N, Nakagawa Y, et al. Web-Based Cognitive Behavioral Therapy Blended With Face-to-Face Sessions for Major Depression: Randomized Controlled Trial. J Med Internet Res. 2018;20(9):e10743-e10743.
  27. Choudhury S, Baker MR, Chatterjee S, Kumar H. Botulinum toxin: an update on pharmacology and newer products in development. Toxins. 2021;13(1):58.
  28. Zargaran D, Zoller F, Zargaran A, Rahman E, Woollard A, Weyrich T, Mosahebi A. Complications of cosmetic botulinum toxin A injections to the upper face: A systematic review and meta-analysis. Aesthet Surg J. 2022;42(5):NP327-NP336.
  29. Rahnama’I MS, Bagheri A, Jahantabi E, Salehi-Pourmehr H, Mostafaei H, Schurch B, et al. Long-term follow-up of intravesical abobotulinumtoxinA (Dysport®) injections in women with idiopathic detrusor overactivity. Asian J Urol. 2022;11(1):93-98.
  30. Chen JJ, Dashtipour K. Abo-, inco-, ona-, and rima-botulinum toxins in clinical therapy: a primer. Pharmacotherapy. 2013;33(3):304-18.
  31. Rupp D, Nicholson G, Canty D, Wang J, Rheaume C, Le L, et al. OnabotulinumtoxinA Displays Greater Biological Activity Compared to IncobotulinumtoxinA, Demonstrating Non-Interchangeability in Both In Vitro and In Vivo Assays. Toxins. 2020;12(6):393.
  32. Camargo CP, Xia J, Costa CS, Gemperli R, Tatini MD, Bulsara MK, Riera R. Botulinum toxin type A for facial wrinkles. Cochrane. Database Sys Rev. 2021;7:011301.
  33. Winayanuwattikun W, Vachiramon V. Botulinum toxin type A for the treatment of skin ulcers: a review article. Toxins. 2022;14(6):406.
  34. Small R. Botulinum toxin injection for facial wrinkles. Am Fam Physician. 2014;90:168-175.
  35. Janes LE, Connor LM, Moradi A, Alghoul M. Current use of cosmetic toxins to improve facial aesthetics. Plast Reconstr Surg. 2021;147:644e-657e.
  36. Phan K, Younessi S, Dubin D, Lin MJ, Khorasani H. Emerging off-label esthetic uses of botulinum toxin in dermatology. Dermatol Ther. 2022;35:e15205.
  37. Hong SO. Cosmetic treatment using botulinum toxin in the oral and maxillofacial area: A narrative review of esthetic techniques. Toxins (Basel). 2023;15(2):82.
  38. Nigam PK, Nigam A. Botulinum toxin. Indian. J. Dermatol. 2010;55(1):8-14.
  39. Halverstam C, Alvarez M. Post-botulinum toxin depigmentation. J Am Acad Dermatol. 2011;AB144-AB144.
  40. Cohen JL, Dayan SH, Cox SE, Yalamanchili R, Tardie G. OnabotulinumtoxinA dose‐ranging study for hyperdynamic perioral lines. Dermatol. Surg. 2012;38(9):1497-1505.
  41. Suksantilap S, Chalermchai T, Paichitrojjana A. Efficacy of intradermal botulinum toxin type A injection technique in the treatment of deep and mixed melasma. Proceed Graduate School Conf. 2022.
  42. Vachiramon V, Anuntrangsee T, Palakornkitti P, Jurairattanaporn N, Harnchoowong S. Incobotulinum Toxin Type A for Treatment of Ultraviolet-B-Induced Hyperpigmentation: A Prospective, Randomized, Controlled Trial. Toxins. 2022;14(6):417.
  43. Jung J-A, Kim B-J, Kim M-S, You H-J, Yoon E-S, Dhong E-S, et al. Protective effect of botulinum toxin against ultraviolet-induced skin pigmentation. Plastic Reconstructive Surg. 2019;144(2):347-356.
  44. Jurairattanaporn N, et al. Study of botulinum toxin type A for the treatment of ultraviolet B‐induced hyperpigmentation: A prospective, randomized, controlled trial. J Cosmetic Dermatol. 2022;21(8):3343-3350.
  45. Wu Q, Xia Y, Dai K, Bai P, Kwan KKL, Guo MSS, et al. Solar light induces the release of acetylcholine from skin keratinocytes affecting melanogenesis. FASEB. J. 2020;34(7):8941-8958.
  46. Enkhtaivan E, Lee C. Role of Amine Neurotransmitters and Their Receptors in Skin Pigmentation: Therapeutic Implication. Int J Mol Sci. 2021;22(15):8071.

How to Cite

Hokky, L. A., Saraswati, M. R. ., Sriwidyani, N. P. ., Artini, I. G. A. ., Widyadharma, I. P. E. ., & Winaya, K. K. . (2024). Effect of botulinum toxin A on tyrosinase and melanin: A literature review. Indonesia Journal of Biomedical Science, 18(1), 110–115. https://doi.org/10.15562/ijbs.v18i1.557

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Liowina Adlin Hokky
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IJBS Journal


Made Ratna Saraswati
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Ni Putu Sriwidyani
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I Gusti Ayu Artini
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I Putu Eka Widyadharma
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Ketut Kwartantaya Winaya
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IJBS Journal