Dual-action cosmetic components: Honey- and pollen-derived extracellular vesicles in attenuating melanogenesis and accelerating epidermal regeneration.

The integumentary system functions as a highly regulated primary barrier, defending the host against environmental stressors while preserving hydration and tissue homeostasis. However, chronic exposure to ultraviolet radiation and exogenous insults precipitates excessive reactive oxygen species (ROS) generation, hyperpigmentation, and impaired epidermal repair. While honey and pollen are well-documented apicultural resources endowed with antioxidant and pro-regenerative properties, the transdermal delivery of their macromolecular active constituents remains a formidable clinical challenge. Here, we introduce honey- and pollen-derived extracellular vesicles (HPEVs) as a highly biocompatible, nanoscale vesicular platform for delivering apicultural bioactives to skin cells. Isolated HPEVs exhibited a highly uniform vesicular morphology with a mean diameter of 168.5-216.5 nm and were effectively internalized by murine melanoma cells and human skin-associated cell lines without any discernible cytotoxicity at concentrations up to 10 μg/mL. In α-melanocyte-stimulating (α-MSH)-activated B16F10 cells, HPEV treatment exerted concentration-dependent anti-melanogenic activity, downregulating microphthalmia-associated transcription factor (MITF) and its downstream effectors, tyrosinase and tyrosinase-related protein-2 (TRP2). Furthermore, in vitro scratch wound assays revealed that HPEVs markedly accelerated keratinocyte motility and migration in HaCaT cells; this effect persisted under mitomycin C-mediated proliferation blockade, indicating a direct enhancement of migratory capacity. To validate cosmetic applications, HPEVs were successfully incorporated into a CICA cream, and the resulting formulation demonstrated excellent physicochemical and rheological stability. Collectively, these findings identify HPEVs as a nature-derived vesicular platform with dual anti-melanogenic and pro-migratory activity in skin-related cell models, supporting their further development for cosmetic approaches to hyperpigmentation and epidermal regeneration.