Exosomes isolated from citrus lemon: a promising candidate for the treatment of Alzheimer's disease

<b>Aim:</b> To investigate the efficacy of exosome-like nanovesicles from citrus lemon (EXO-CLs) in combating oxidative stress associated with Alzheimer's disease. <b>Materials &amp; methods:</b> EXO-CLs were isolated through differential ultracentrifugation, characterized for particle size and evaluated for antioxidant activity. <b>Results:</b> EXO-CLs exhibited a mean size of 93.77 ± 12.31 nm, demonstrated permeability across the blood–brain barrier (BBB) and displayed antioxidant activity comparable to ascorbic acid. Additionally, they were found to be non-toxic, with over 80% cell viability observed in SH-SY5Y cells. <b>Conclusion:</b> The study proposes that EXO-CLs could serve as an effective treatment for neurodegenerative diseases. This suggests a promising approach for targeted interventions in brain-related disorders, owing to the antioxidant properties and BBB permeability exhibited by EXO-CLs. Plant exosomes contain bioactive compounds that potentially offer health benefits. Similarly, exosomes isolated from citrus lemons have demonstrated various properties, including antioxidant, anti-inflammatory and anticancer effects. Numerous compounds derived from plants have been studied for their potential neuroprotective effects and their capacity to impact processes linked to Alzheimer's disease. The <i>in vitro</i> PAMPA assay illustrated the capability of EXO-CL to permeate the lipid bilayer, indicating its potential to reach the brain for the treatment of neurological disorders. The <i>in vitro</i> antioxidant study validated the antioxidant capabilities of the formulated EXO-CL. In cell culture studies, EXO-CL exhibited strong cytocompatibility with neuroblastoma cells and demonstrated the ability to mitigate neurodegeneration induced by β-amyloid in SH-SY5Y cells. The outcomes from the Alzheimer's disease treatment using EXO-CL have proven satisfactory. Our findings suggest that EXO-CL could function as a neuroprotective agent, supported by its demonstrated ability to penetrate the blood–brain barrier, its antioxidant activity, compatibility with neuroblastoma cells and its capacity to protect against toxicity induced by β-amyloids. Further, <i>in vivo</i> animal studies are crucial to advancing the development of EXO-CL as a potential neuroprotective agent for neurodegenerative disorders.