Development of perilla essential oil-based nanoemulsions as anti-psoriatic and dermal delivery platforms for topical therapy.

Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation, immune dysregulation, and impaired barrier regeneration, highlighting the need for safe and effective topical therapies. Perilla essential oil (PO) contains a rich profile of long-chain fatty acids and lipid-related metabolites with reported anti-inflammatory and barrier-modulating activities. However, its clinical utility is limited by its volatility and poor stability. In this study, we developed PO-based nanoemulsions (PO-NEs) to preserve bioactive components while enabling dermal delivery. GC-MS analysis confirmed that the oil was dominated by fatty acids and related lipid metabolites relevant to cutaneous inflammation and epidermal repair. PO-NEs significantly inhibited keratinocyte proliferation in vitro, reduced the expression of key proinflammatory cytokines, and lowered intracellular ROS accumulation. In a mouse model of imiquimod-induced psoriasis, topical application of 5% PO-NEs markedly improved erythema, scaling scores, epidermal hyperplasia, and inflammatory cell infiltration. RNA sequencing demonstrated that PO-NEs broadly reprogrammed lesional gene expression, with enrichment of pathways related to extracellular matrix organization, epidermal differentiation, and immune regulation and pronounced suppression of aberrantly activated Wnt/β-catenin signaling, which was further supported by targeted qRT-PCR validation. Building on this bioactive carrier, we next encapsulated curcumin into PO-NEs (Cur@PO-NEs) and compared with curcumin suspensions and curcumin-loaded medium-chain triglycerides (MCT) nanoemulsions. Cur@PO-NEs exhibited superior skin permeation and intradermal deposition, and produced the most pronounced improvements in clinical scores, histopathology, and inflammatory readouts. Comprehensive local and systemic safety evaluations indicate good tolerability and biocompatibility. Together, these findings identify PO-NEs as a natural bioactive nanoemulsion capable of modulating epidermal signaling and the psoriatic microenvironment and establish Cur@PO-NEs as a synergistic and safe topical strategy for psoriasis therapy that combines carrier-mediated bioactivity with enhanced curcumin delivery.