Discovery of functional characteristics of plant cell suspension-derived extracellular vesicles on the in vitro cerebrovascular inflammation

Extracellular vesicles (EVs) are essential biomolecule carriers responsible for intercellular communication. They play vital roles in many physiological events. Thanks to their bilayer lipid membrane, biomolecules can be protected from the harsh extracellular environment. One of living organisms in which EVs consistently function is plants. Plant-derived EVs (PDEVs) have a role in physiological events and defense against pathogens. Besides, these nanovesicles showed therapeutic potential in antioxidant, anti-inflammatory, and immunomodulatory activities. On the other hand, cerebrovascular inflammation (CVI) is a chronic inflammatory disorder characterized by cerebrovascular dysfunction, proinflammatory phenotype, and vascular hyperpermeability. Based on their therapeutic activities, PDEVs can become a promising tool for cerebrovascular disorders. Our study aims to investigate the functionality of plant cell suspension extracellular vesicles (PCSEVs) and their therapeutic effects on the in vitro CVI model. To that end, these nanovesicles were purified from the media of Stevia rebaudiana, Vaccaria hispanica and characterized. The CVI pathology was modelled and the effects of PCSEVs were investigated. In the results, first, the PCSEVs were successfully purified and characterized in the sense of physical and molecular properties. Besides, the CVI pathology was successfully modelled in the cells and it exhibited critical features of its pathologies. Lastly, it was observed that PCSEVs led to a protective response in the CVI model, and these effects mainly occurred by modulating adhesion molecule expression via the NRF2 pathway. In addition, further analysis revealed that these effects of PCSEVs were mediated through the phosphorylation of key signaling pathways. However, further studies are needed to transform these in vitro results into clinical applications. Future studies should include in vivo experiments in animal models to confirm the efficacy and safety of the PCSEVs. By demonstrating the therapeutic effects of PCSEVs on cerebrovascular inflammation, our study paves the way for innovative, plant-derived nanomedicine solutions for vascular diseases.