Dual-targeting antioxidant and anti-glycation strategy inhibits melanogenesis through clinical and mechanistic study

Hyperpigmentation constitutes a significant dermatological challenge, exacerbated by oxidative stress and glycation. This study aims to develop and evaluate a novel dual-effect composition (DEC) that integrates antioxidant agents (ergothioneine and tocopheryl glucoside) and antiglycation agents (decarboxy carnosine and naringin) for the management of hyperpigmentation. A multi-model approach was employed to comprehensively assess DEC efficacy. In vitro studies on A875 melanoma cells showed DEC lowered reactive oxygen species (ROS) level, enhanced Nrf2 and superoxide dismutase (SOD) expression, suppressed advanced glycation end-product (AGE)-RAGE signaling, and reduced tyrosinase (TYR) levels and melanin production. Using the MelaFulKutis™ 3D pigmented skin model under UV and methylglyoxal exposure, the DEC-containing serum also reduced melanin deposition and downregulated microphthalmia-associated transcription factor (MITF) and TYR expression by 63.37% and 80.39%, respectively. In a clinical trial involving 34 Asian participants, DEC-containing serum significantly improved skin lightness (ΔL*: +0.98%, P = 0.003), reduced facial sallowness (Δb*: -5.92%, P < 0.001), decreased skin autofluorescence (SAF: -14.23, P < 0.001), and received 97% participant satisfaction after 56 days. In conclusion, DEC effectively targets both oxidative stress and glycation pathways to inhibit melanogenesis, highlighting the potential of dual-targeting approaches in hyperpigmentation treatment.