Protective effect of a novel metal-phenolic network composite against ultraviolet-induced skin damage by modulating MAPK/AP-1/NF-κB signaling pathways and attenuating oxidative stress in human keratinocytes

Ultraviolet irradiation is a major inducer of oxidative stress, inflammation, and extracellular matrix degradation in skin, which contribute to photoaging. Melamax®, a novel metal-phenolic network (MPN)-based composite hair dye, was primarily developed as an eco-friendly alternative to conventional oxidative dyes. We hypothesized that Melamax® could exert photoprotective effects against ultraviolet-induced oxidative stress, extracellular matrix degradation, and barrier dysfunction. To confirm this, we investigated the protective effects of Melamax® against ultraviolet-induced cellular damage. Transcriptomic profiling using a three-dimensional skin model revealed that Melamax® pretreatment mitigated ultraviolet-induced gene expression changes by suppressing pathways related to matrix degradation, inflammation, and oxidative stress, and enhanced antioxidant defense and hydration-associated genes. Consistently, in HaCaT keratinocytes, Melamax® significantly reduced hydrogen peroxide and ultraviolet-induced reactive oxygen species; downregulated MMP-1, MMP-3, and p16; and restored TIMP-1 expression. Inflammatory cytokines, including IL-6, IL-1β, IL-8, and TNF-α, were markedly attenuated. Antioxidant and protective factors, such as Nrf2, catalase, SOD2, and HAS2 were upregulated. Mechanistic studies further showed that Melamax® inhibited phosphorylation of MAPKs, including ERK, JNK, and p38, and suppressed the activation of AP-1 and NF-κB signaling. Collectively, these findings demonstrate that Melamax®, originally developed as an eco-friendly hair dye material, also confers potent protection against ultraviolet-induced oxidative and inflammatory damage in keratinocytes, highlighting its potential as a dual-purpose agent for both cosmetic coloration and skin photoprotection.