Ursolic Acid-Based Oleolite for Hyperpigmentary Disorders: Molecular Mechanisms and Clinical Efficacy

Skin-lightening molecules have gained widespread attention for their relevance in both cosmetic applications and the treatment of dermatological disorders. Hyperpigmentation and skin spots can be counteracted by suppressing oxidative stress, inhibiting tyrosinase activity, or regulating the expression of tyrosinase-related proteins (TYRP-1 and TYRP-2) and the microphthalmia-associated transcription factor (MITF). Among natural compounds, ursolic acid (UA), a triterpene primarily found in apple peel was investigated for its potential depigmenting properties. In this study, UA was extracted in oil form from Annurca apple (AAO) to formulate a standardized oleolite (784.40 ± 7.58 mg/mL) and evaluate its efficacy through in vitro and clinical models. AAO exhibited tyrosinase inhibitory activity and significantly reduced melanin content in A375 melanoma cells, accompanied by decreased expression of TYRP-1, TYRP-2, and MITF, as well as modulation of oxidative stress markers. These effects were confirmed in a randomized, double-blind, placebo-controlled clinical trial, in which a topical formulation containing 2.5% AAO significantly improved skin hyperpigmentation compared to placebo. Overall, the results highlight AAO as a promising natural agent for managing skin hyperpigmentation through multiple mechanisms, suggesting its potential utility in both cosmetic and dermatological settings.