The immunomodulatory potential of a medicinal plant-derived exosome-like nanovesicles and their applications in inflammatory skin disorders 2258926

Introduction Chronic immune-mediated skin disorders such as psoriasis and atopic dermatitis are characterized by epidermal hyperproliferation, barrier dysfunction, and cytokine-driven inflammation. Dysregulated production of proinflammatory cytokines perpetuates keratinocyte and immune cell activation. Current therapies, including biologics, are accompanied by side effects, which necessitate safer, more accessible, and non-immunosuppressive alternatives. Plant-derived exosome-like nanovesicles (PDENs) are emerging as biocompatible nanotherapeutics with the capacity to serve as immunomodulatory natural delivery vehicles. This project aimed to explore the immunomodulatory potential of PDENs derived from Dendrobium fimbriatum Hook (DF) stems, a traditional Chinese medicinal herb, in suppressing inflammatory responses in immune-mediated skin diseases. Methods PDENs were isolated from DF stems via differential ultracentrifugation and sucrose-density gradient ultracentrifugation (DF-PDENs). Nanoparticle tracking analysis was used to evaluate size distribution and particle yield. Human keratinocyte models were stimulated with TNF-α and IL-17 to simulate skin inflammation, and murine T-cell models were stimulated with IL-17 and IFN-γ to investigate molecular mechanisms and pathways. Cytokine secretion (IL-6, IL-8) was measured via ELISA, and Western blotting was used to elucidate the intersection with key molecular inflammation pathways. Results DF-PDENs exhibited high purity and stability, as confirmed by nanoparticle tracking analysis. Treatment with DF-PDENs significantly reduced IL-6 and IL-8 production in TNF-α- and IL-17-stimulated keratinocytes. Preliminary signalling analyses revealed attenuation of inflammation-associated molecular pathways. Conclusion DF-PDENs demonstrated anti-inflammatory activity in vitro, supporting their potential as a novel nanotherapeutic for treating immune-mediated skin diseases, such as psoriasis.