Abstract
AIM: This study evaluates the therapeutic potential of Pterostilbene (PTN), a natural stilbenoid, in an imiquimod (IMQ)-induced psoriasis model. Due to PTN's poor solubility and bioavailability, a pterostilbene nano-emulsion gel (PTN-NEG) formulation (0.1% and 0.2% w/w) was developed to enhance its therapeutic efficacy. METHODS: Psoriasis was induced in C57BL/6J mice by applying IMQ (62.5 mg/day) on a 5 cm(2) shaved dorsal skin area for 7 days. PTN-NEG was topically applied, and its effects on oxidative stress, inflammatory cytokines (IL-17, TNF-α, IL-22), NF-κB pathway activation, and keratinocyte proliferation markers (Ki-67, Bcl-xL) were assessed. The expression of dual-specificity phosphatase-1 (DUSP-1) and its role in modulating mitogen-activated protein kinase (MAPK) signaling were evaluated. Additionally, DNA methyltransferase-1 (DNMT-1) inhibition was examined to explore PTN's epigenetic impact. RESULTS: PTN-NEG restored antioxidant balance, reduced pro-inflammatory cytokines, inhibited NF-κB activation, and suppressed keratinocyte proliferation. It unregulated DUSP-1, modulating MAPK signaling and preventing psoriasis progression. PTN-NEG also improved epidermal structure, reduced hyperplasia, and prevented splenomegaly. Notably, PTN inhibited DNMT-1, suggesting a novel epigenetic mechanism for psoriasis. CONCLUSION: To our knowledge, this study is the first to demonstrate that PTN-NEG mitigates psoriasis through anti-inflammatory, antioxidant, and epigenetic regulatory mechanisms, highlighting its therapeutic potential in psoriasis management.