Melanogenic activity of fish scale-derived peptides FTGML from grass carp:An integrated study of molecular docking, network pharmacology and animal experiments

Abstract

Tyrosinase activity directly determines the amount of melanin synthesis, therefore the search for safe, naturally-derived tyrosinase inhibitors is a challenge for the whitening industries. The grass carp scale-derived peptides FTGML with strong tyrosinase inhibitory activity was obtained in the former study. Within this research, exploring and modeling the interaction mechanism of FTGML with tyrosinase, FTGML exhibited a lower binding energy (−7.2 kcal/mol) than kojic acid, whereas the stable interactions of ligands with proteins within molecular dynamics simulations provided backing for these results. Network pharmacology revealed that the potential targets of FTGML to inhibit melanin deposition were MMP9/GSK3B/MAPK1, etc., and by regulating signaling pathways including PI3K-AKT. In addition, ADMET demonstrated that FTGML remained bioactive, non-toxic, non-harmful and non-sensitizing to the skin after oral administration, and could be used for oral administration and direct application to the skin. Moreover, FTGML increased skin water content, decreased tyrosinase activity in skin and serum, and reduced melanin deposition in mouse skin, which further verified that FTGML could promote skin whitening and repair after UV damage. Collectively, FTGML is expected to be used in the whitening industry as a novel, safe and naturally sourced tyrosinase inhibitor.