Impact of nano-chitosan solution on psoriasis-like thin skin lesion induced by imiquimod in Wistar rats: Exploring novel epigenetic role targeting miR-155, JAK2/STAT3/RORC/IL-17A, and MyD88/NF-κB pathways.

BACKGROUND: Psoriasis is a chronic, relapsing, immune-mediated skin disorder manifested by keratinocyte hyperproliferation. Current therapies provide symptomatic relief but carry the risk of severe side effects. Chitosan, a natural biopolymer, has wound-healing and anti-inflammatory properties in various dermatological applications. AIM: This study aimed to assess the impact of chitosan solution on psoriasis-like skin lesions induced by imiquimod (IMQ) in a Wistar rat model. METHODS: An IMQ-induced psoriatic skin lesion was induced in Wistar rats; 35 rats were divided equally into: Control, IMQ, IMQ + acetic acid, IMQ + chitosan (5 g/L), and IMQ + chitosan (10 g/L) groups. Macroscopic, histopathological, immunohistochemical, biochemical, and molecular analyses were conducted to assess morphological and structural alterations, inflammatory responses, oxidative stress markers, and gene expression profiles. RESULTS: Application of IMQ resulted in psoriatic-like morphological and histopathological skin alterations. Chitosan application ameliorated these alterations and significantly reduced the erythema, desquamation, and skin thickening. Histological evaluation revealed that chitosan solution reduced epidermal acanthosis, hyperkeratosis, and inflammatory infiltrates while improving dermal architecture. It also suppressed PCNA and S100 expression, markers for keratinocyte proliferation and inflammation, respectively. Biochemically, it reduced IL-6, p-JAK2, p-STAT3, IL-17A, MyD88, and NF-κB levels, while restoring redox balance by decreasing MDA and enhancing catalase activity. Furthermore, qRT-PCR analysis demonstrated chitosan-mediated downregulation of miR-155 and RORC, highlighting its immunomodulatory effect. CONCLUSION: Nano-Chitosan solution effectively mitigated IMQ-induced psoriasis-like skin lesions, with better efficacy for the higher dose, through cytoprotective, anti-inflammatory, antioxidant, and immunoregulatory mechanisms. It has the ability to target the JAK2/STAT3/RORC/IL-17A and MyD88/NF-κB pathways via downregulating miR-155, which reveals a novel molecular mechanism for chitosan's beneficial effects and suggests its potential as an alternative therapeutic strategy for psoriasis.