Comparative Efficacy of Skin-Lightening Formulations in Suppressing Ultraviolet B (UVB)-Induced Arachidonic Acid, Alpha-Melanocyte-Stimulating Hormone (α-MSH), and Melanin Expression: An In Vitro Keratinocyte-Melanocyte Co-culture Study

Background: Melasma is a chronic hyperpigmentary disorder exacerbated by sun exposure, characterized by asymptomatic hyperpigmented macules and patches. Its pathogenesis involves ultraviolet B (UVB)-induced activation of melanogenesis pathways, including arachidonic acid (AA) metabolism, alpha-melanocyte-stimulating hormone (α-MSH) secretion, and melanin synthesis. This study aimed to evaluate the efficacy of a multi-ingredient skin-lightening formulation (3% tranexamic acid, 2% ascorbyl glucoside, 2.5% arbutin, and 5% niacinamide) compared to a 10% vitamin C preparation and 4% hydroquinone (HQ) in suppressing UVB-induced AA, α-MSH, and melanin production in a keratinocyte-melanocyte co-culture model. Methods: Keratinocyte-melanocyte co-cultures were pretreated with the multi-ingredient formulation, 10% vitamin C, or 4% HQ before UVB irradiation (150 mJ/cm2). Distilled water served as the negative control. Biomarkers (AA, α-MSH, and melanin) were quantified using enzyme-linked immunosorbent assay (ELISA) and fluorometric assay. Results: UVB irradiation significantly increased AA (4.3-fold), α-MSH (3.7-fold), and melanin (2.6-fold) levels compared to unirradiated cells (all p < 0.001). All tested formulations reduced AA levels compared to the negative control (p < 0.001), with the multi-ingredient formulation demonstrating superior efficacy over both 10% vitamin C and 4% HQ (p < 0.001). Only the multi-ingredient formulation significantly suppressed α-MSH levels (p < 0.001). Regarding melanin reduction, the multi-ingredient formulation achieved comparable efficacy to 4% HQ but outperformed 10% vitamin C (p < 0.05). Conclusion: The multi-ingredient formulation demonstrated superior efficacy in reducing UVB-induced AA and α-MSH levels while achieving comparable melanin reduction to 4% HQ. These results are consistent with the prevailing consensus that effective melasma management necessitates a multifaceted approach that concurrently targets multiple mechanisms.