A COMPREHENSIVE REVIEW ON A SKIN-BRIGHTENING AGENT KOJIC ACID AND ITS APPLICATIONS

Main Article Content

Prantika Mondal
Dr. Vijay Bhalla
Reena Tyagi

Keywords

hyperpigmentation, tyrosinase inhibitor, food industry, de-pigmentation, kojic acid, melasma

Abstract

This article reviews the Kojic Acid (KA) as a skin-brightening agent which produced industrially by Aspergillus species in aerobic fermentation and its application in the cosmetics industry. In 1907, Saito discovered KA, a natural product; it has since become one of the most investigated skin-brightening agents. The KA plays an important role in determining certain chemical and physical properties it possesses. KA has different applications in various fields. These days kojic acid performs a vital function, prevention of UV radiation it extensively utilized in whitening creams and lotions because of its anti-tyrosinase activity. It shows other utilization as an anti-inflammatory and analgesic agent in the medical field, an anti-bacterial agent in food industry, and an anti-browning agent for agriculture products. It also has some drawbacks, such as the KA is highly unstable upon exposure air and sunlight it changes its color and the other drawback is cytotoxicity which may be overcome by way of the formation of kojic acid peptides which are more stable. It was shown to be helpful in the treatment of hyper pigmentary disorders, such as freckles, age spots, post-inflammatory hyperpigmentation, and melasma, which has been proven clinically.

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References

1. Beélik, A. in Advances in carbohydrate chemistry Vol. 11 145-183 (Elsevier, 1956).
2. Rosfarizan M, Mohamed MS, Nurashikin S, Saleh MM, Ariff AB. Kojic acid: Applications and development of fermentation for production. Biotechnology and Molecular Biology. 2010;5(2):24-37.
3. El-Aziz ABA. Improvement of kojic acid production by a mutant strain of Aspergillus Flavus. Journal of Natural Sciences Research. 2013;3(4):31-41.
4. Brtko J, Rondahl L, Fickova M, Hudecova D, Eybl V, Uher M. Kojic acid and its derivatives: History and present state of art. Central European Journal of Public Health. 2004;12:16-18.
5. Burdock, G. A., Soni, M. G., & Carabin, I. G. (2001). Evaluation of health aspects of kojic acid in food. Regulatory Toxicology and Pharmacology, 33(1), 80Y101. doi:10.1006/rtph.2000.1442
6. Gonc¸alez, M. L., Correˆa, M. A., & Chorilli, M. (2013). Skin delivery of kojic acid-loaded nanotechnology-based drug delivery systems for the treatment of skin aging. BioMed Research International, 2013, 271276. doi:10.1155/2013/271276
7. Monteiro, R. C., Kishore, B. N., Bhat, R. M., Sukumar D., Martis, J., & Ganesh, H. K. (2013). A comparative study of the efficacy of 4% hydroquinone vs 0.75% kojic acid cream in the treatment of facial melasma. Indian Journal of Dermatology, 58(2), 157. doi:10.4103/ 0019-5154.108070
8. Lim, J. T. (1999). Treatment of melasma using kojic acid in a gel containing hydroquinone and glycolic acid. Dermatologic Surgery, 25(4), 282Y284.
9. Bentley, R. From miso, sake and shoyu to cosmetics: a century of science for kojic acid. Nat. Prod. Rep. 23, 1046-1062 (2006).
10. Brtko, J. et al. Kojic acid and its derivatives: history and present state of art. Central european journal of public health 12, S16-S17 (2004).
11. Chaudhary, J. Production Technology and Applications of Kojic Acid. Annu. Res. Rev. Biol. 2014, 4, 3165–3196. [CrossRef]
12. Saeedi, M.; Eslamifar, M.; Khezri, K. Kojic acid applications in cosmetic and pharmaceutical preparations. Biomed. Pharmacother. 2019, 110, 582–593. [CrossRef] [PubMed]
13. Chib, S.; Dogra, A.; Nandi, U.; Saran, S. Consistent production of kojic acid from Aspergillus sojae SSC-3 isolated from rice husk. Mol. Biol. Rep. 2019, 46, 5995–6002. [CrossRef] [PubMed]
14. Masse, M.O.; Duvallet, V.; Borremans, M.; Goeyens, L. Identification and quantitative analysis of kojic acid and abrotine in skin-whitening cosmetics. Int. J. Cosmet. Sci. 2001, 23, 219–232. [CrossRef] [PubMed]
15. Rosfarizan, M.; Mohamed, M.S.; Suhaili, N.; Salleh, M.M.; Ariff, A.B. Kojic acid: Applications and development of fermentation process for production. Biotechnol. Mol. Biol. Rev. 2010, 5, 24–37.
16. Gomes, C.; Silva, A.C.; Marques, A.C.; Lobo, S.; Amaral, M.H. Biotechnology Applied to Cosmetics and Aesthetic Medicines. Cosmetics 2020, 7, 33. [CrossRef]
17. Kim, J.H. Enhancement of commercial antifungal agents by Kojic acid. Int. J. Mol. Sci. 2012, 13, 13867–13880. [CrossRef]
18. Ola, A.R.B. Single production of Kojic acid by Aspergillus flavus and the revision of flufuran. Molecules 2019, 24, 4200. [CrossRef]
19. Velliou, E.G. In vitro Studies. Model. Optim. Control Biomed. Syst. 2017, 233–264. [CrossRef]
20. Yabuta T. The constitution of kojic acid: A d-pyrone derivative formed by Aspergillus flavus from carbohydrates. Journal of Chemical Society Transaction. 1924;125:575- 587.
21. Uchino K, Nagawa M, Tonosaki Y, Oda M, Fukuchi A. Kojic acid as an anti-spec agent. Agricultural and Biological Chemistry. 1988;52(10):2609-2670.
22. Arnstein HRV., Bentley R. The biosynthesis of kojic acid: the incorporation of labeled small molecules into kojic acid. Biochemistry. 1953;54:517-522.
23. Kitada M, Ueyama H, Fukimbara T. Studies on kojic acid fermentation: Cultural condition in submerged culture. Journal of Fermentation Technology. 1967;45:1101- 1107.
24. Kitada M, Kenaeda J, Miyazaki K, Fukimbara T, Studies on Kojic Acid (VI) production and recovery of kojic acid on industrial scale. Journal of Fermentation Technology. 1971;49(2):343-349.
25. Crueger W, Crueger A. A Textbook of Industrial Microbiology. 2nd ed. London: Sinauer Associates Inc; 1984.
26. Nakajima N, Ishihara K, Hamada H. Functional glucosylation of kojic acid and daidzein with the Eucalyptus membrane-associated UDP-glucosyltransferase reaction system. Journal of Bioscience & Bioengineering. 2001;92:469–471.
27. Beelik A. Kojic acid. Advance in Carbohydrate Chemistry. 1956;11:145-183.
28. Feng, W.; Liang, J.; Wang, B.; Chen, J. Improvement of kojic acid production in Aspergillus oryzae AR-47 mutant strain by combined mutagenesis. Bioprocess Biosyst. Eng. 2019, 42, 753–761. [CrossRef] [PubMed]
29. Couteau, C.; Coiffard, L. Overview of Skin Whitening Agents: Drugs and Cosmetic Products. Cosmetics 2016, 3, 27. [CrossRef]
30. Khezri, K.; Saeedi, M.; Morteza-Semnani, K.; Akbari, J.; Hedayatizadeh-Omran, A. A promising and effective platform for delivering hydrophilic depigmenting agents in the treatment of cutaneous hyperpigmentation: Kojic acid nanostructured lipid carrier. Artif. Cells Nanomed. Biotechnol. 2021, 49, 38–47. [CrossRef]
31. Davis, E. C. & Callender, V. D. Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color. The Journal of clinical and aesthetic dermatology 3, 20 (2010).
32. Draelos, Z. D. Skin lightening preparations and the hydroquinone controversy. Dermatologic Therapy 20, 308-313 (2007).
33. Goldstein, B. G., Goldstein, A. O. & Callender, V. D. Learn how UpToDate can help you.
34. Deri, B. The unravelling of the complex pattern of tyrosinase inhibition. Sci. Rep. 2016, 6, 34993. [CrossRef] [PubMed]
35. Lai, X.; Wichers, H.J.; Dijkstra, B.W. Structure and Function of Human Tyrosinase and Tyrosinase- Related Proteins. Chem. A Eur. J. 2018, 24, 47–55. [CrossRef] [PubMed]
36. Chang, T.S. An updated review of tyrosinase inhibitors. Int. J. Mol. Sci. 2009, 10, 2440–2475. [CrossRef]
37. Kim, H., Choi, H. R., Kim, D. S., & Park, K. C. (2012). Topical hypopigmenting agents for pigmentary disorders and their mechanisms of action. Annals of Dermatology, 24(1), 1Y6. doi:10.5021/ad. 2012.24.1.1
38. Deo, K. S., Dash, K. N., Sharma, Y. K., Virmani, N. C., & Oberai, C. (2013). Kojic acid vis-a-vis its combinations with hydroquinone and betamethasone valerate in melasma: A randomized, single blind, comparative study of efficacy and safety. Indian Journal of Dermatology, 58(4), 281Y285. doi:10.4103/0019-5154.113940
39. Burnett, C.L. Final report of the safety assessment of kojic acid as used in cosmetics. Int. J. Toxicol. 2010, 29. [CrossRef] [PubMed]
40. Mann, T. Inhibition of Human Tyrosinase Requires Molecular Motifs Distinctively Different from Mushroom Tyrosinase. J. Invest. Dermatol. 2018, 138, 1601–1608. [CrossRef] [PubMed]
41. Chambers, C. Opinion on kojic acid. Sci. Committees Consum. Prod. 2008, 1–79.
42. Goldstein, B. G., Goldstein, A. O., & Callender, V. D. (2014). Melasma. In R. P. Dellavalle & R. C. Corona (Eds.), UpToDate. Retrieved from http://www.uptodate.com/contents/melasma
43. García‐Gavín, J., González‐Vilas, D., Fernández‐Redondo, V. & Toribio, J. Pigmented contact dermatitis due to kojic acid. A paradoxical side effect of a skin lightener. Contact Dermatitis 62, 63-64 (2010).
44. Aytemir MD, Karakaya G. Kojic acid derivatives. Medicinal chemistry and drug design. 1 sted. Rijeka: Intech; 2012.
45. Kwak, S.Y.; Choi, H.R.; Park, K.C.; Lee, Y.S. Kojic acid-amino acid amide metal complexes and their melanogenesis inhibitory activities. J. Pept. Sci. 2011, 17, 791–797. [CrossRef]
46. Seyedeh Mahdieh Hashemi, S.E. Kojic acid-derived tyrosinase inhibitors: Synthesis and bioactivity. Pharm. Biomed. Res. 2015, 1, 1–17. Available online: http://pbr.mazums.ac.ir (accessed on 10 May 2022).
47. Hariri, R.; Saeedi, M.; Akbarzadeh, T. Naturally occurring and synthetic peptides: Efficient tyrosinase inhibitors. J. Pept. Sci. 2021, 27, 1–10. [CrossRef]
48. Pillaiyar, T.; Namasivayam, V.; Manickam, M.; Jung, S. H Inhibitors of Melanogenesis: An Updated Review. J. Med. Chem. 2018, 61, 7395–7418. [CrossRef]
49. Beelik A, Purves CB. Some new reactions and derivatives of kojic acid. Canadian Journal of Chemistry. 1955;33(8):1361-1374.
50. Reddy BVS, Reddy MR, Madan C, Kumar KP, Rao MS. Indium (III) chloride catalyzed three component coupling reaction: Novel synthesis of 2- substituted aryl (indolyl) kojic acid derivatives as potent antifungal and antibacterial agents. Bioorganic and medicinal chemistry letters. 2010;20(24):7507-7511.
51. Sadeghi B, Shahedi MR. A clean simple and efficient synthesis of 2-substituted aryl (indolyl) kojic acid derivatives by kaolin/Ag nano-composites as a reusable catalyst: A green protocol, Journal of Chemistry. 2013;7.
52. Nurchi VM, Lachowicz JI, Crisponi G, Murgia S, Arca M, Pintus A, Gans P, Gutierrez JN, Martin AD, Castineiras A, Remelli M, Szewczuk Z, Lis T. Kojic acid derivatives as powerful chelators for iron (III) and aluminium (III). International journal of inorganic, organo-metallic and bioinorganic chemistry. 2011;22:5984-5998.
53. McNail JH, Yuen VG, Hoveyda HR, Orgive C. Bis (Maltolato) oxovanadium (IV) is a potent insulin mimic. Journal of Medicinal Chemistry.1992;35(8):1489-1491.
54. Wei YB, Yang X. Synthesis, characterization and anti-diabetic therapeutic potential of a new benzyl acid-derivatized kojic acid vanadyl complex. Biometals. 2012;25:1261- 1268.
55. Owolabi, J.O.; Fabiyi, O.S.; Adelakin, L.A.; Ekwerike, M.C. Effects of skin lightening cream agents - hydroquinone and kojic acid, on the skin of adult female experimental rats. Clin. Cosmet. Investig. Dermatol. 2020, 13, 283–289. [CrossRef]
56. Wang, X.R. Intercalation assembly of kojic acid into Zn-Ti layered double hydroxide with antibacterial and whitening performances. Chinese Chem. Lett. 2019, 30, 919–923. [CrossRef]
57. Nurunnabi, T. Antimicrobial activity of kojic acid from endophytic fungus Colletotrichum gloeosporioides isolated from Sonneratia apetala, a mangrove plant of the Sundarbans. Asian Pac. J. Trop. Med. 2018, 11, 350–354. [CrossRef]
58. Van Tran, V.; Loi Nguyen, T.; Moon, J.Y.; Lee, Y.C. Core-shell materials, lipid particles and nanoemulsions, for delivery of active anti-oxidants in cosmetics applications: Challenges and development strategies. Chem. Eng. J. 2018, 368, 88–114. [CrossRef]
59. Zhang, J. Kojic acid-mediated damage responses induce mycelial regeneration in the basidiomycete Hypsizygus marmoreus. PLoS ONE 2017, 12, e0187351. [CrossRef]
60. Lajis, A.F.B.; Hamid, M.; Ariff, A.B. Depigmenting effect of kojic acid esters in hyperpigmented B16F1 melanoma cells. J. Biomed. Biotechnol. 2012, 2012, 952452. [CrossRef]
61. Brtko, J.; Rondahl, L.; Ficková, M.; Hudecová, D.; Eybl, V.; Uher, M. Kojic acid and its derivatives: History and present state of art. Cent. Eur. J. Public Health 2004, 12, S16–S17. [CrossRef]
62. Lee, M.; Rho, H.S.; Choi, K. Anti-inflammatory Effects of a P-coumaric Acid and Kojic Acid Derivative in LPS-stimulated RAW264.7 Macrophage Cells. Biotechnol. Bioprocess Eng. 2019, 24, 653–657. [CrossRef]
63. Li, T.; Liang, J.; Liu, L.; Shi, F.; Jia, X.; Li, M. Fitoterapia Novel kojic acid derivatives with anti-inflammatory effects from Aspergillus versicolor. Fitoterapia 2021, 154, 105027. [CrossRef] [PubMed]
64. De, A. Hyperpigmentation Case Kojic Acid in the Management of Melasma: An Effective Therapeutic Weapon. Indian J. Dermatol. 2019, 1–4.
65. Kobayashi M, Nishikawa K, Yamamoto M. Hematopoietic regulatory domain of gata1 gene is positively regulated by GATA1 protein in zebra-fish embryos. Development. 2001;128(12):2341-2350.
66. Gomes, C.; Silva, A.C.; Marques, A.C.; Lobo, S.; Amaral, M.H. Biotechnology Applied to Cosmetics and Aesthetic Medicines. Cosmetics 2020, 7, 33. [CrossRef]
67. Jimbow K, Minamitsuji Y. Topical therapies for melasma and disorder of hyper- pigmentation. Dermatologic Therapy. 2001;14:35-45.
68. Ambrogi V, Perioli L, Nocchetti M, Latterini L, Pagano C, Massetti E, Rossi C. Immobilization of kojic acid on ZnAl-hydrotalcite like compounds. Journal of Physics and Chemistry of Solids. 2012;73(1):94-98.
69. El-Kady, I.A.; Zohri, A.N.A.; Hamed, S.R. Kojic Acid Production from Agro-Industrial By-Products Using Fungi. Biotechnol. Res. Int. 2014, 2014, 642385. [CrossRef]
70. Ozturk G, Erol DD, Uzbay T, Aytemir MD. Synthesis of 4(IH)-Pyridmone derivatives and investigation of analgesic and anti-inflammatory activities. II Farmaco. 2001;56:251-256.
71. Kayahara H, Shibata N, Tadasa K, Maedu H, Kotani T, Inchimoto I. Amino acids and peptide derivatives of kojic acid and their antifungal properties. Agricultural and Biological Chemistry. 1990;54(9):2441-2442.
72. Emami S, Ghafouri E, Faramarzi MA, Samadi N, Irannejad H, Foroumadi A. Mannich bases of 7-piperazinylquinolones and kojic acid derivatives: synthesis, in vitro antibacterial activity and in silico study. European Journal of Medicinal Chemistry. 2013;68:185-191.
73. Lucas SD, Goncalves LM, Carvalho LAR, Correia HF, Da Costa EMR, Guedes RA, Moreira R, Guedes RC. Optimization of O3-Acyl kojic acid derivatives as a potent and selective human neutrophil elastase inhibitor. Journal of Medicinal Chemistry. 2013;56(23):9802-9806.
74. Toso L, Crisponi G, Nurchi VM, Alonso MC, Lachowicz, Mansoori D, Arca M, Santos A, Marques SA, Gano L, Gutierrez JN, Perez JMG, Martin AD, Choquesillo-Lazarte D, Szewczuk Z. A family of hydroxylpyrone ligands designed and synthesized as iron chelators. Journal of Inorganic Biochemistry. 2013;127:220-231.
75. Mohammadpour M, Behjati M, Sadeghi A, Fassihi A. Wound healing by topical application of antioxidant Iron chelators: kojic acid and deferiprone. Research in Pharmaceutical Sciences. 2012;7(5).
76. Son SM, Moon KD, Lee CY. Inhibitory effects of various anti-browning agents on apple slices. Food Chemistry. 2000;73:23-30.
77. Kaatz H, Streffer K, Wollenberger U, Peter MG. Inhibition of mushroom tyrosinase by kojic acid octanoates. Zeitschrift Für Naturforschung B. 1999;54:70-74.
78. Liu X, Xia W, Jiang Q, Xu Y, Yu P. Synthesis, characterization and antimicrobial activity of kojic acid grafted chitosan oligosaccharides. Journal of Agriculture and Food Chemistry. 2014;62(1):297-303.
79. Kwak SY, Noh JM, Park JSH, Byun W, Choi HR, Park KC, Lee YS. Enhanced cell permeability of kojic acid-phenyl alanine amide with metal complex. Bioorganic and Medicinal Chemistry Letters. 2010;20(2):738-741.
80. Novotny L, Rauko P, Abdel-Hamid M, Vachalkova A (1999). Kojic acid - A new leading molecule for a preparation of compounds with an antineoplastic potential. Neoplasma 46: 89-92
81. Buchta K. Organic acids of minor importance. In: Rehm HJ, Reed GH, Editors. Biotechnology: A comprehensive treaties. Weinheim: Verlag Chemie. 1983;3.
82. Wilson BJ (1971). Miscellaneous Aspergillus toxins. In Ciegler A (ed.) Microbes Toxins, Fungal Toxins VI, Academic Press, New York.
83. Tatsumi C, Ichimoto I, Uchida S, Nonomura S. Production of comenic acid from kojic acid by microorganism. Fermentation Technology. 1969;47(3):178-184.
84. Szklarzewicz J, Peciorek P, Zabierowski P, Kurpiwska K, Mikuriya M, Yoshioka D. Synthesis, crystal structures and spectroscopic studies of Mo (Iv) complexes synthesized in reactions with kojic acid, maltol and ethyl maltol. Polyhedron. 2012;37(1):35-41.
85. Nurchi VM, Lachowicz JI, Crisponi G, Murgia S, Arca M, Pintus A, Gans P, Gutierrez JN, Martin AD, Castineiras A, Remelli M, Szewczuk Z, Lis T. Kojic acid derivatives as powerful chelators for iron (III) and aluminium (III). International journal of inorganic, organo-metallic and bioinorganic chemistry. 2011;22:5984-5998.