Arctiin attenuates the development of psoriasis-like dermatitis and modulates EGFR-associated ERK signaling

Background Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by keratinocyte hyperproliferation, immune cell infiltration, and increased dermal angiogenesis. Although current therapies provide symptomatic relief, long-term disease control remains challenging. Arctiin (ARC), a major lignan glycoside of Arctii Fructus from Arctium lappa L., exerts anti-inflammatory and immunomodulatory effects on several inflammatory diseases. However, the effects of ARC on psoriasis-like inflammation and the signaling mechanisms involved remain unclear. Purpose To investigate the effects of ARC in psoriasis-related experimental models and elucidate the signaling pathways involved. Methods The effects of oral ARC administration were evaluated in an imiquimod-induced psoriasis-like dermatitis model. Clinical severity, histopathology, immune cell infiltration, dermal vascular changes, and inflammatory gene expression were assessed. An exploratory network analysis, together with a transcriptomic analysis of publicly available human psoriasis datasets, was used to prioritize signaling nodes for experimental investigation. In primary human keratinocytes, ARC-mediated inflammatory and signaling responses were evaluated using RT‒qPCR and immunoblotting. Results Oral ARC administration attenuated the development of imiquimod-induced psoriasis-like skin lesions; reduced epidermal hyperplasia, immune cell infiltration, and dermal angiogenesis; and downregulated inflammatory mediator expression. The exploratory network analysis recurrently prioritized epidermal growth factor receptor (EGFR) among several candidate signaling nodes, whereas human psoriasis transcriptomic data revealed increased expression of multiple EGFR ligands in lesional skin and supported the relevance of EGFR-associated signaling in epidermal keratinocytes. In keratinocytes, ARC reduced the expression of psoriasis-associated inflammatory mediators and suppressed the phosphorylation of EGFR, ERK, and JNK. EGFR knockdown abolished the additional suppressive effect of ARC on ERK phosphorylation, whereas the suppression of JNK phosphorylation persisted. EGFR knockdown also attenuated the inhibitory effects of ARC on the expression of several psoriasis-related inflammatory mediators. Consistent with the cellular findings, ARC administration was associated with reduced EGFR, ERK, and JNK phosphorylation in imiquimod-treated skin. Conclusion ARC attenuates the development of psoriasis-like inflammation and is associated with the modulation of EGFR-associated ERK signaling. These findings suggest that ARC may represent a potential candidate treatment for psoriasis.