Inhibitory Effect of Avenanthramides (Avn) on Tyrosinase Activity and Melanogenesis in α-MSH-Activated SK-MEL-2 Cells: In Vitro and In Silico Analysis

Melanin causes melasma, freckles, age spots, and chloasma. Anti-melanogenic agents can prevent disease-related hyperpigmentation. In the present study, the dose-dependent tyrosinase inhibitory activity of Avenanthramide (Avn)-A-B-C was demonstrated, and 100 mu M Avn-A-B-C produced the strongest competitive inhibition against inter-cellular tyrosinase and melanin synthesis. Avn-A-B-C inhibits the expression of melanogenesis-related proteins, such as TRP1 and 2. Molecular docking simulation revealed that AvnC (-7.6 kcal/mol) had a higher binding affinity for tyrosinase than AvnA (-7.3 kcal/mol) and AvnB (-6.8 kcal/mol). AvnC was predicted to interact with tyrosinase through two hydrogen bonds at Ser360 (distance: 2.7 angstrom) and Asn364 (distance: 2.6 angstrom). In addition, AvnB and AvnC were predicted to be skin non-sensitizers in mammals by the Derek Nexus Quantitative Structure-Activity Relationship system.

Automated summary

Melanin-related pigmentation disorders can be prevented by anti-melanogenic agents like Avenanthramide (Avn)-A-B-C, which demonstrated dose-dependent tyrosinase inhibitory activity, with Avn-A-B-C showing the strongest competitive inhibition against intracellular tyrosinase and melanin synthesis. AvnC was found to have a higher binding affinity for tyrosinase than AvnA and AvnB, and was predicted to interact with tyrosinase through two hydrogen bonds at specific amino acid residues. Additionally, AvnB and AvnC were predicted to be non-sensitizers in mammals.