Phytochemical Characterization and In Vitro Anti-Tyrosinase Activity of a Traditional Hypericum perforatum L. Olive Oil Macerate for Cosmetic Applications

Hypericum perforatum L. olive-oil macerate is a traditional topical remedy whose wound-healing efficacy is well documented, yet the phytochemical and mechanistic basis of its cosmetic-relevant activity remains poorly defined. This study provides an integrated experimental and in silico characterization of a traditionally prepared macerate of defined origin. The fatty acid composition, oxidative-stability indices, total phenolic and flavonoid contents, naphthodianthrone level, antioxidant capacity, and tyrosinase inhibition were determined, and the principal constituents were examined by molecular docking and in silico skin-permeation and toxicity profiling. The olive-oil matrix was oleic acid-dominated (73.9%) and oxidatively stable (iodine value 86.0; oxidizability index, COX, 1.84), while the macerate showed modest phenolic (36.84 μg pyrocatechol equivalents, PCE/mg) and naphthodianthrone (0.044 mg/mL hypericin equivalents) contents. It showed limited antioxidant activity but moderate tyrosinase inhibition (38.75% at 200 μg/mL). Docking revealed that, despite high affinity scores, the naphthodianthrones lay 7–9 Å from the catalytic copper centre (an artefact of the scoring function), whereas fatty acids accessed the active site more closely, implicating the matrix in the observed activity. In silico profiling indicated that the photoactive naphthodianthrones are largely retained at the skin surface. These findings link this centuries-old preparation to a mechanistically informed understanding of its cosmetic potential.