Phytochemicals from Stellera chamaejasme alleviate psoriasis by modulating the immune microenvironment via the JAK2/PI3K/AKT pathway

Stellera chamaejasme L., a traditional Chinese medicinal herb used for treating skin disorders such as psoriasis, was investigated to identify its bioactive antipsoriatic components and elucidate its underlying mechanisms of action. In an imiquimod (IMQ)-induced psoriasis-like skin lesion mouse model, the ethyl acetate (Et) fraction exhibited the most significant therapeutic effect among various solvent-partitioned extracts, as demonstrated by hematoxylin-eosin (H&E), immunohistochemistry (IHC), and immunofluorescence (IF) analyses. The bioassay-guided fractionation of the Et extract led to the isolation of eleven compounds (1-11), whose structures were characterized using nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography. Among them, wikstroelide J (WJ, compound 11) exhibited the most potent activity, inhibiting M5-induced hyperproliferation of HaCaT keratinocytes (IC₅₀ = 9.4 μM) and alleviating psoriasis-like skin lesions in vivo. Mechanistically, WJ modulated T-cell subsets and downregulated the JAK2/PI3K/AKT signaling pathway, with pathway involvement further supported by the use of the JAK2 inhibitor AG490. These findings highlight WJ as a promising antipsoriatic agent that targets the JAK2/PI3K/AKT pathway. Future studies will aim to improve its pharmacological properties and assess its efficacy in clinical settings, although current limitations, such as a lack of pharmacokinetic and clinical data, remain to be addressed.