Unveiling the Melanin Inhibition and Photoprotection of Lemon Peel Extracts through Liquid Chromatography-Mass Spectrometry and Molecular Docking Analysis

Ultraviolet (UV) radiation is an important environmental stressor that stimulates melanin accumulation and causes skin damage that may lead to skin cancer. In the present study, focusing on lemon peel ethanol extract (LPEE) and lemon peel water extract (LPWE), the inhibitory effects of these extracts on melanin synthesis and their photoprotective properties against UVB radiation were investigated. Both extracts significantly inhibited tyrosinase activity in a dose-dependent manner. At a concentration of 10 mg/mL, LPEE and LPWE demonstrated inhibition rates of 60.3% and 70.6%, respectively. In particular, LPEE showed a more pronounced inhibitory effect on melanin in B16-F10 cells compared to LPWE. At a concentration of 2.5 mg/mL, LPEE attained a melanin inhibition rate of 44.3%. In addition, both extracts showed strong free radical scavenging activity, particularly against ABTS radicals. At a concentration of 0.05 mg/mL, they can achieve over 84% ABTS radical scavenging effect. When their concentration was 0.625 mg/mL, both can effectively protect cells from UVB damage and maintain cell viability. Comprehensive analysis using liquid chromatography-mass spectrometry (LC-MS/MS) identified 344 metabolites in both extracts, mainly phenolic compounds and carboxylic acids. LPWE and LPEE exhibited 180 distinct compounds, with 139 of these compounds demonstrating an upregulation in LPWE relative to LPEE. Molecular docking was used to predict the interactions of these compounds with proteins involved in melanin synthesis and apoptosis. Brassinolide, N-acetylneuraminic acid, all-trans-retinoic acid, and beta-carotene emerged as potential melanin inhibitors. In addition, hesperidin and kaempferol-3-O-rutinoside showed significant binding affinity for proteins associated with UVB-induced apoptosis. In conclusion, the present study provides valuable insights into the bioactive compounds of lemon peel extracts and highlights their potential as inhibitors of melanin production and UVB-induced apoptosis. These findings open new avenues for the development of cosmetic and dermatological products.