Kojic acid

Kojic acid is a fungus-derived tyrosinase inhibitor with metal-chelating activity (IC₅₀=182.7μM). Kojic acid inhibits the conversion of L-tyrosine to L-DOPA to reduce melanin production and exerts antibacterial effects by enhancing antioxidant activity. Kojic acid can be used for research on pigmentation disorders such as melasma, skin whitening, food anti-browning, and antibacterial preservation^[1-4].

In vitro, treatment of A375 cells with 8μg/mL Kojic acid for 24h downregulated tumor suppressor-related genes including APOBEC1, ARHGEF16, CD22, FGFR3, GALNT1, UNC5C, and ZNF146^[5]. Treatment of corneal endothelial cells with 1mM Kojic acid for 7 days enhanced cell migration and downregulated galectin 8 and laminin α1 expression^[6]. Treatment of HaCaT and SCC-13 cells transfected with pNF-κB-SEAP-NPT plasmid with 10mM Kojic acid inhibited NF-κB activation in the cells^[7].

In vivo, intra-articular injection of 10μL 20μM Kojic acid into the knee joint twice weekly for 8 weeks in a mouse model of arthritis reduced cartilage destruction and osteophyte formation, reversed decreases in subchondral bone BV/TV and Tb.Th, increased aggrecan expression, decreased MMP13 expression, and lowered OARSI scores^[8]. Subcutaneous injection of 75mg/kg or 300mg/kg Kojic acid 27h before 8Gy (lethal dose) gamma irradiation increased survival rates and promoted recovery of white blood cells, red blood cells, hemoglobin, hematocrit, and platelets in C57BL/6 mice^[9]. Oral administration of 50mg/kg/day Kojic acid every other day for 3 weeks in LPS-induced C57BL/6N mice decreased expression of TLR4, Iba-1, GFAP, p-JNK, p-NF-κB, TNF-α, and IL-1β in the brain, reduced LPO and ROS levels, increased Nrf2 and HO-1, and reduced neuronal shrinkage in the cortex and hippocampal DG, CA1, and CA3 regions^[10].

References:
[1] Saeedi M, Eslamifar M, Khezri K. Kojic acid applications in cosmetic and pharmaceutical preparations. Biomed Pharmacother. 2019 Feb;110:582-593.
[2] Suryadi H, Irianti MI, Septiarini TH. Methods of Random Mutagenesis of Aspergillus Strain for Increasing Kojic Acid Production. Curr Pharm Biotechnol. 2022;23(4):486-494.
[3] Sharma S, Singh S, Sarma SJ. Challenges and advancements in bioprocess intensification of fungal secondary metabolite: kojic acid. World J Microbiol Biotechnol. 2023 Mar 30;39(6):140.
[4] Zilles JC, Dos Santos FL, Kulkamp-Guerreiro IC, et al. Biological activities and safety data of kojic acid and its derivatives: A review. Exp Dermatol. 2022 Oct;31(10):1500-1521.
[5] Cheng S-L, Liu R H, Sheu J-N, et al. Toxicogenomics of Kojic Acid on Gene Expression Profiling of A375 Human Malignant Melanoma Cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
[6] Wei X, Luo D, Yan Y, et al. Kojic acid inhibits senescence of human corneal endothelial cells via NF-κB and p21 signaling pathways. Exp Eye Res. 2019;180:174-183.
[7] Li J, Yu G, He Z, et al. Kojic acid alleviates osteoarthritis by attenuating inflammation and restoring impaired autophagy through regulating NF-kB and PI3K/AKT/mTOR signaling pathways: An in vivo and in vitro study. Int Immunopharmacol. 2025;147:114022.
[8] Zhong C-C, Xu Z, Gan J, et al. Acute Ongoing Nociception Delays Recovery of Consciousness from Sevoflurane Anesthesia via a Midbrain Circuit. J Neurosci. 2024 Aug 21;44(34):e0740242024.
[9] Wang K, Liu C, Di C, et al. Kojic Acid Protects C57BL/6 Mice from Gamma-irradiation Induced Damage. Asian Pac J Cancer Prev. 2014;15(1):291-297.
[10] Ali W, Choe K, Park JS, et al. Kojic acid reverses LPS-induced neuroinflammation and cognitive impairment by regulating the TLR4/NF-kB signaling pathway. Front Pharmacol. 2024 Aug 9;15:1443552.