Natural plant-derived nanovesicles for effective psoriasis therapy via dual modulation of IL-17 and NRF2 pathway

Psoriasis is an inflammatory skin disease with aberrant epidermal differentiation and chronic inflammation. Plant-derived exosome-like nanovesicles (PDNVs) are exosome-mimetic structures isolated from plants with enhanced bioavailability and solubility. Herein, we investigated the therapeutic efficacy of PDNVs for psoriasis treatment. In our initial phenotype-driven screen, PDNVs from apple, garlic, and shallot displayed both pro-differentiation and anti-inflammatory activity in vitro. In imiquimod (IMQ)-induced psoriasis-like murine model, topical application of either shallot or garlic PDNV hydrogels led to complete recovery of normal skin phenotype. In porcine skin ex vivo assay, both shallot and garlic PDNVs displayed percutaneous penetration up to the suprabasal epidermis. Using next generation sequencing and quantitative mRNA profiling in keratinocytes and murine skin, we elucidated a suppressive effect of shallot and garlic PDNVs on IL-17 signaling via modulation of upstream nuclear factor erythroid-2-related factor 2 (NRF2) pathway. Since PDNVs are economical to produce, shallot and garlic PDNVs could be natural and cost-effective topical alternative for psoriasis.