Kojic AcidvsTranexamic Acid

Kojic acid (5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) inhibits tyrosinase through copper chelation—tyrosinase is a type-3 copper enzyme requiring two copper ions to catalyze tyrosine to L-DOPA and L-DOPA to dopaquinone. By sequestering copper, kojic acid renders tyrosinase inactive. May also inhibit tyrosinase-related protein-1 (TRP-1). Exhibits direct antioxidant activity, scavenging superoxide and hydroxyl radicals. Relatively unstable—oxidizes with air and light, forming brown degradation products that lose activity; opaque, airtight packaging and low pH improve stability. Kojic dipalmitate is a more stable ester but requires enzymatic cleavage, reducing potency. Contact sensitization can develop with prolonged use.

Tranexamic acid (TXA) is a lysine analogue that competitively inhibits plasminogen activation—binding lysine-binding sites and preventing conversion to plasmin by tPA and uPA. Plasmin normally activates multiple pathways: converts latent TGF-beta to active form, stimulates keratinocyte release of arachidonic acid and prostaglandins (PGE2, PGF2-alpha), and increases SCF and bFGF—all stimulating melanocyte proliferation and melanogenesis. By blocking plasmin, TXA interrupts this paracrine cascade, reducing melanin through a mechanism independent of tyrosinase. TXA also inhibits VEGF and reduces angiogenesis—addressing melasma's vascular component. May reduce UV-induced plasmin in keratinocytes. This unique mechanism makes TXA synergistic with tyrosinase inhibitors for stubborn melasma.