Lobetyolin alleviates IMQ‑induced psoriasis‑like skin inflammation by maintaining the homeostasis of the skin and inhibiting the inflammatory cytokines in dendritic cells.

Psoriasis, the most common inflammatory skin disease, is marked by excessive proliferation of keratinocytes and infiltration of immune cells into the epidermis. Current treatments, particularly biologics targeting the IL‑23/IL‑17 axis, demonstrate excellent efficacy, but issues of recurrence and side effects persist. Therefore, it is essential to identify safer and more effective alternatives. Lobetyolin (LBT), a key component of polyacetylenes in Codonopsis pilosula, exhibits potent antioxidant and antitumor properties, yet its potential for treating psoriasis remains unexplored. In the present study, it was found that topical treatment with LBT significantly inhibits psoriasis in mice and maintains skin homeostasis during disease progression by regulating genes associated with keratinocyte proliferation and differentiation, enhancing the PPAR signaling pathway, and upregulating genes and metabolites involved in linoleic acid metabolism. Additionally, LBT suppressed gene expression linked to cytokine activity as well as the Il17, Tnf and MAPK signaling pathways in IMQ‑treated dendritic cells (DCs). These findings underscored LBT's efficacy in reducing IMQ‑induced psoriasis‑like skin inflammation by preserving skin homeostasis and inhibiting inflammatory cytokines in DCs. The present results suggested that topically applied LBT could serve as a promising drug candidate for psoriasis treatment or as an adjunct to biologic therapies to prevent disease relapse.