Tanshinone I Ameliorates Psoriasis-Like Dermatitis by Suppressing Inflammation and Regulating Keratinocyte Differentiation.

Background: Psoriasis is an immune-related inflammatory systemic condition characterized by dysregulated keratinocyte proliferation and chronic inflammation. Tanshinone I (Tan-I) has recently been discovered to have immunomodulatory properties, but its role and mechanisms in treating psoriasis remain unclear. Objective: To evaluate the efficacy of Tan-I in the treatment of psoriasis and to determine the mechanisms involved. Methods: An imiquimod (IMQ)-induced psoriasis-like mouse model was treated topically with Tan-I (7.5 mg/kg/d) or a vehicle. Disease severity was evaluated using the Psoriasis Area and Severity Index (PASI), and histological changes were assessed via H&E staining and Ki67 immunofluorescence. TNF-α-stimulated HaCaT keratinocytes were used for in vitro analyses, including apoptosis, cell cycle progression, and inflammatory gene expression via RT-qPCR. RNA sequencing (RNA-seq) was performed to investigate Tan-I's mechanisms in vivo and in vitro, while keratin expression was analyzed by immunofluorescence and Western blot. Results: Tan-I treatment significantly alleviated psoriasis-like lesions in the IMQ mouse model, improving skin pathology and reducing Ki67-positive cells. RNA-seq revealed that Tan-I modulated immune pathways, keratinocyte differentiation, and barrier function. In TNF-α-stimulated HaCaT cells, Tan-I induced G1-phase cell cycle arrest, reduced apoptosis, and suppressed inflammatory gene expression. RNA-seq further showed that Tan-I normalized cell cycle signaling and apoptosis pathways disrupted by TNF-α. Additionally, Tan-I restored keratin expression patterns, increasing K1 and decreasing K6 and K17 levels in both mouse skin and HaCaT cells. Conclusion: Tan-I is a promising therapeutic candidate for psoriasis, effectively mitigating inflammation, normalizing keratinocyte differentiation, and inhibiting abnormal keratinocyte apoptosis.