Milk Protein-Derived Antioxidant Tetrapeptides as Potential Hypopigmenting Agents

Excessive accumulation of melanin can cause skin pigmentation disorders, which may be accompanied by significant psychological stress. Although many natural and synthetic products have been developed for the regulation of melanogenesis biochemistry, the management of unwanted skin pigmentation remains challenging. Herein, we investigated the potential hypopigmenting properties of peptide sequences that originated from milk proteins such as kappa-casein and beta-lactoglobulin. These proteins are known to inhibit melanogenesis and their hydrolysates are reported as antioxidant peptides. We synthesize tetrapeptide fragments of the milk protein hydrolysates and investigate the amino acids that are essential for designing peptides with tyrosinase inhibitory and antioxidant activities. We found that the peptide methionine-histidine-isoleucine-arginine amide sufficiently inhibits mushroom tyrosinase activity, shows potent antioxidant activity and effectively impedes melanogenesis in cultured melanocytes via cooperative biological activities. Our findings demonstrate the potential utility of the bioactive tetrapeptide from milk proteins as a chemical alternative to hypopigmenting agents.