Edible plant-derived nanovesicles from Abelmoschus manihot exhibit dual functions in inhibiting melanogenesis and promoting IL-6-mediated cytoprotection

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Excessive oxidative stress and dysregulated melanogenesis accelerate skin aging and contribute to pathological skin alterations. Here, we investigated plant-derived nanovesicles from Abelmoschus manihot (AM-PDNVs), an edible plant widely used in functional foods, as bioactive nanomaterials for skinrotection. In α-melanocyte-stimulating hormone (α-MSH)-stimulated melanocytes, AM-PDNVs attenuated melanogenesis via extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) signaling. Concurrently, AM-PDNVs promoted cell proliferation and enhanced antioxidant capacity while reducing reactive oxygen species (ROS). In staurosporine (STS)-induced keratinocytes, AM-PDNVs inhibited apoptosis by modulating PI3K/AKT and suppressing mitochondrial apoptotic markers, including Bax and cleaved caspases-3/−9. Notably, while AM-PDNVs reduced pro-inflammatory cytokines such as IL-1β and IL-8, they markedly upregulated IL-6. Functional assays using recombinant IL-6 and neutralizing antibodies demonstrated IL-6 as a key mediator of AM-PDNV-induced cytoprotection. Collectively, these findings suggest AM-PDNVs as promising food-derived nanomaterials for alleviating hyperpigmentation and oxidative injury, highlighting a novel cytoprotective role for IL-6.