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

Area of Science:

• Dermatology
• Biochemistry
• Cosmetic Science

Background:

• Hyperpigmentation is a common skin concern.
• Oxidative stress and glycation significantly worsen hyperpigmentation.
• Current treatments often target single pathways, limiting efficacy.

Purpose of the Study:

• To develop and evaluate a novel dual-effect composition (DEC) for hyperpigmentation management.
• DEC integrates antioxidant and antiglycation agents to target key pathways.
• Assess DEC efficacy using in vitro, 3D skin models, and clinical trials.

Main Methods:

• In vitro studies on A875 melanoma cells assessed reactive oxygen species (ROS), Nrf2, superoxide dismutase (SOD), advanced glycation end-product (AGE)-RAGE signaling, tyrosinase (TYR), and melanin.
• A 3D pigmented skin model (MelaFulKutis™) evaluated melanin deposition and gene expression (microphthalmia-associated transcription factor (MITF), TYR) under UV and methylglyoxal exposure.
• A 56-day clinical trial on 34 Asian participants measured skin lightness, sallowness, and skin autofluorescence (SAF).

Main Results:

• In vitro: DEC reduced ROS, enhanced Nrf2/SOD, suppressed AGE-RAGE signaling, and decreased TYR/melanin.
• 3D model: DEC serum reduced melanin deposition and downregulated MITF/TYR expression.
• Clinical trial: DEC serum significantly improved skin lightness, reduced sallowness and SAF, with 97% participant satisfaction.

Conclusions:

• DEC effectively targets both oxidative stress and glycation pathways to inhibit melanogenesis.
• The dual-targeting approach of DEC demonstrates significant potential for hyperpigmentation treatment.
• DEC offers a novel and effective solution for managing hyperpigmentation.