Seaweed-Derived Bioactives with Anti-Tyrosinase Activity: A Potential for Skin-Whitening Cosmetics with in silico and in vitro approaches

Seaweed is a promising source of bioactive compounds with potential applications in skincare, particularly for addressing hyperpigmentation. This study investigated the chemical profiles and biological activities of hydrophilic and lipophilic extracts from Sargassum polycystum, Caulerpa lentillifera, and Gracilaria fisheri. LC-MS and GC-MS analyses identified 8 and 112 compounds in hydrophilic and lipophilic extracts, respectively. Among these, G. fisheri lipophilic extracts exhibited the strongest anti-tyrosinase activity. Molecular docking identified eight compounds with low binding affinities comparable to kojic acid and tropolone, while ADMET predictions highlighted stigmasterol for its favorable skin permeability and safety. In vitro cytotoxicity assays confirmed its low toxicity (IC50 = 3.38 ± 0.28 µg/mL) with no adverse effects at 0.006 µg/mL. Trypsin stability assays and molecular docking against serine proteases (trypsin and chymotrypsin) showed no significant off-target interactions. These findings suggest stigmasterol as a safe, selective, and effective natural tyrosinase inhibitor for potential use in skin-whitening formulation.