Kojic acid (5-hydroxy-2-hydroxymethyl-4H-pyrane-4-one, KA) (8), a naturally occurring hydrophilic fungal derivative evolved from certain species of Acetobacter, Asperigillus and Penicillium, is used in the treatment of hyperpigmentation disorders (9). Its molecular formula is C6H6O4 5, and its molecular weight is 142.1. It also eliminates free radicals, strengthens the activity of cells and keeps the food fresh.
The depigmetation action of kojic acid is attributed to the chelating ability (10), even if an interference with different steps of melanin synthesis (11) and inhibition of nuclear factor-kappa B (NF-kappa B) activation in keratinocytes, contrasting with the hyperpigmentation associated with inflammatory response (12). It is a kind of specialized inhibitor for melanin for preventing the tyrosinase activity through synthesizing with copper ion in the cells after it enters skin cells. KA and its derivative have better inhibitory effect on tyrosinase than any other skin whitening agents. At present it is assigned into various kinds of cosmetics for curing freckles, age spots, pigmentation, and acne. It has been used alone in concentration 2-4% and it has also been combined with HQ 2% in an AHA gel base (13).
KA dipalmitate is a modified kojic acid derivative, which not only overcomes the instability to light, heat, and metallic ion, but also keeps the inhibitory tyrosinase activity
and prevents the forming of melanin. As fat-soluble skin whitening agent, it is more easily absorbed by skin. Kojic acid has the potential for causing contact dermatitis and erythema (14). The heterozygous p53-deficient CBA mice were fed a diet containing 0%, 1.5%, and 3% KA for 26 weeks. KA induced diffuse hypertrophy and hyperplasia of the thyroid follicular epithelial cells and tumorigenic potential in the liver (15).