Objective: Environmental factors like ultraviolet (UV) radiation and air pollution accelerate extrinsic skin aging by inducing reactive oxygen species (ROS), leading to oxidative stress and cellular damage. This study investigated the protective potential of Dimethylmethoxy Chromanol (DMMC) and Vignaangularis seed extract, both unpreserved (AZK) and preserved (XPO) forms, individually and in combination, using invitro, exvivo, and clinical evaluations. Methods: Primary human skin cells and pigmented skin equivalents were exposed to UVA/UVB, H2O2, or PM2.5. Assessments included immunofluorescence, protein carbonylation, malondialdehyde (MDA) quantification, comet assays, and LC-MS/MS analysis for oxidative DNA/RNA lesions. Transcriptomic profiling analyzed DMMC-induced gene expression. A 28-day, randomized, double-blind, placebo-controlled clinical hemi-face study (n = 33) assessed wrinkle reduction via PRIMOS 3D imaging. Results: AZK rapidly reduced oxidative DNA/RNA lesions in keratinocytes under combined stressors. DMMC exerted a dual mechanism: direct radical scavenging and transcriptional activation of antioxidant, detoxification, and efflux genes. It protected against pyrene/UVA genotoxicity, UVB-induced protein oxidation, and H2O2 cytotoxicity. In pigmented skin models, co-treatment with XPO and DMMC further elevated loricrin, Ki67, and COL VII levels relative to XPO. monotherapy, while reducing protein carbonylation and lipid peroxidation. Clinically, the combined formulation significantly reduced wrinkle depth at day 28 compared to placebo. Conclusion: DMMC and Vignaangularis Seed Extract provide complementary protection against environmental skin stress. AZK offers rapid antioxidative defense, while DMMC bolsters acute and long-term cellular resilience. Their combination restores epidermal structural integrity in exvivo skin models and relieves facial wrinkling in human clinical testing, supporting their application in anti-photoaging skincare formulations.
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