Abstract
Rosa damascena exhibits diverse biological activities, including antimicrobial, antioxidant, anti-inflammatory, cardioprotective, neuroprotective, and skin-protective effects, largely attributed through its rich phytochemical composition. In parallel, plant-derived nanovesicles (PD-NVs) have emerged as natural nanocarriers that transport bioactive cargos capable of modulating recipient cell functions across kingdoms. In this study, Rosa damascena derived nanovesicles (RD-NVs) were isolated by ultracentrifugation and characterized by Transmission electron microscopy, nanoparticle tracking analysis, zeta potential measurement, and SDS-PAGE to confirm their vesicular nature, size distribution, and protein cargo profile. LC‒MS/MS-based proteomics, followed by annotation against NCBI and UniProt, and comparative BLASTP mapping to plant and human proteins, revealed 75 proteins shared with plant, Arabidopsis and human orthologs, which were further analyzed using interaction networks and hub detection together with GO and KEGG enrichment. RD-NVs (size, 40-100 nm; surface charge, -25 to -40 mV) carry proteins involved mainly in plastid transcription, ribosomal function, and photosynthetic electron transport in plants, whereas human mapped orthologs were enriched in oxidative phosphorylation, mitochondrial function, arginine-proline, taurine, and hypotaurine metabolism, suggesting that RD-NV hub proteins may interfere with metabolic pathways associated with obesity, insulin resistance, fatty liver, type 2 diabetes, and related inflammatory and neuroinflammatory disorders. Moreover, the peptides of the RD-NVs revealed similarities with multiple reported antimicrobial peptides therefore, might actively participate in plant and human defense system. Overall, this study reveals that the RD-NV proteome contains conserved pathways that may support metabolic and immune-related functions in cross-kingdom contexts. To validate cross-kingdom interaction in vitro, the RD-NVs were treated with the RAW264.7 macrophage which showed significant biocompatibility with a particle range of up to 8.94 × 108 and cellular internalization.