4‑Hydroxyacetophenone is an Antipigmentation Reagent via Inhibiting Tryrosinase Activity

This study investigates the skin-whitening potential of 4-Hydroxyacetophenone (4-HAP), a compound commonly used as a preservative in cosmetics. Despite its widespread use, its whitening activity has not been extensively reported. Our preliminary research identified several commercial cosmetic formulations exhibiting whitening effects without known whitening agents. We hypothesized that 4-HAP might be a key ingredient. To test this, we employed a mushroom tyrosinase model, B16 mouse melanoma cells, and zebrafish to systematically evaluate the whitening activity of 4-HAP. Our findings demonstrate that 4-HAP is a potent tyrosinase inhibitor, significantly reducing melanin content in vitro and in vivo. Additionally, molecular docking and dynamics analyses revealed that the stable binding of 4-HAP to tyrosinase is crucial for its whitening effect. In formulations containing 2% 4-HAP, human skin models showed nearly complete recovery from UV-induced pigmentation after 4 weeks, while control groups exhibited persistent UV marks. These results confirm the efficacy of 4-HAP as a stable whitening agent in cosmetic formulations, highlighting its potential for further development in skin lightening products. This study has confirmed that 4-HAP holding the potential to become an effective whitening ingredient in the cosmetics field.