Microbial Antioxidants Reduce ROS In Human Skin Cells Under Oxidative Stress

Abstract Reactive oxygen species (ROS) play a dual role in cellular homeostasis, but excessive levels of ROS lead to oxidative stress, accelerating skin aging. Environmental stressors like UV radiation induce ROS overproduction, overwhelming endogenous antioxidant defenses and causing cellular damage. While the skin possesses an intrinsic antioxidant network that provides moderate protection, excessive oxidative stress can trigger inflammatory responses, thereby necessitating exogenous antioxidant intervention. Microbe-derived antioxidants (MA), produced via probiotic fermentation of sea buckthorn and chestnut rose, have shown promise in mitigating ROS-induced damage. In this study, we evaluated two MA formulations, MA1 and MA2, for their ability to scavenge free radicals and alleviate hydrogen peroxide (H 2 O 2 )-induced oxidative stress in human dermal fibroblasts (HDF) and dermal papilla cells (HDP). Both formulations displayed dose-dependent DPPH radical scavenging activity and enhanced cell viability at low concentrations. Under H 2 O 2 -induced oxidative stress, MA1 and MA2 effectively restored intracellular ROS to baseline levels, demonstrating significant cytoprotective effects. UHPLC–MS/MS profiling identified 12 compounds shared by both formulations, and Gene Ontology Biological Process enrichment analysis revealed that their associated target genes were significantly enriched in antioxidant-related pathways. Five compounds—adenosine, citric acid, 5-hydroxymethylfurfural, myricetin, and phenylalanine—emerged as key contributors to the observed antioxidative effects. Together, these findings highlight the potential of fermented microbial antioxidants to re-establish redox homeostasis in human skin cells and support their further development as therapeutic or cosmetic interventions targeting oxidative stress and skin aging. Given the heightened oxidative sensitivity of aged fibroblasts, MA’s ability to alleviate ROS may offer novel therapeutic strategies against skin aging and related pathologies.