Abstract
Background/Objectives: Voglibose, an α-glucosidase inhibitor commonly prescribed to manage postprandial hyperglycemia in diabetes mellitus, demonstrates potential for repurposing as an anti-melanogenic agent. This study aims to explore the inhibitory effects of voglibose on melanogenesis and elucidate its molecular mechanisms, highlighting its possible applications in treating hyperpigmentation disorders. Methods: The anti-melanogenic effects of voglibose were investigated using B16F10 melanoma cells. Cell viability, melanin content, and tyrosinase activity were assessed following voglibose treatment. Western blot analysis was performed to examine changes in melanogenic proteins and transcription factors. The role of signaling pathways, including PKA/CREB, MAPK, PI3K/AKT, and GSK3β/β-Catenin, was analyzed. Primary human skin irritation tests were conducted to evaluate the topical safety of voglibose. Results: Voglibose significantly reduced melanin synthesis and tyrosinase activity in B16F10 cells in a dose-dependent manner. Western blot analysis revealed decreased expression of MITF, TRP-1, and TRP-2, indicating the inhibition of melanogenesis. Voglibose modulated key signaling pathways, including the suppression of PKA/CREB, MAPK, and AKT activation, while restoring GSK3β activity to inhibit β-catenin stabilization. Human skin irritation tests confirmed voglibose's safety for topical application, showing no adverse reactions at 50 and 100 μM concentrations. Conclusions: Voglibose demonstrates anti-melanogenic properties through the modulation of multiple signaling pathways and the inhibition of melanin biosynthesis. Its safety profile and efficacy suggest its potential as a repurposed drug for managing hyperpigmentation and advancing cosmeceutical applications.