Abstract
Skin hyperpigmentation represents a common aesthetic and dermatological concern, often resulting from excessive melanin synthesis and oxidative stress. Effective skin-lightening strategies target these processes by inhibiting tyrosinase activity, modulating melanogenic regulators, and enhancing antioxidant defenses. Ursolic acid, a natural triterpene abundant in apple peel, has shown potential as a safe and multifunctional skin-brightening molecule. In this study, an apple oil extract rich in ursolic acid (Annurca Apple Oleolite, AAO) was developed and standardized to 784.40 ± 7.58 µg/mL. The extract demonstrated significant tyrosinase inhibition and a marked reduction in melanin content in A375 melanoma cells, accompanied by downregulation of TYRP-1, TYRP-2, and MITF expression and modulation of oxidative stress markers. These molecular effects were confirmed in a randomized, double-blind, placebo-controlled clinical trial involving 42 subjects with hyperpigmented skin. Topical application of a formulation containing 2.5% AAO for 28 days significantly reduced UV and brown spot scores (-6.4% and - 4.1%, respectively; p < 0.001), decreased melanin index (-10.2%, p < 0.001), and improved skin brightness and tone uniformity (ITA° +12.4%; L* +3.1%; both p < 0.001) compared with 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 formulations.