Chrysoeriol Alleviates Psoriasis Inflammation and Keratinocyte Hyperproliferation Possibly Through Inhibiting AKT/NF-κB Signaling Activation.

PURPOSE: Chrysoeriol (CHR), a naturally derived and non-toxic compound, exhibits potent immunomodulatory and anti-inflammatory activities. This investigation assessed CHR's anti-inflammatory effects and elucidated the mechanism. METHODS: For assessing CHR's anti-psoriatic efficacy, imiquimod (IMQ)-induced murine models and LPS-treated HaCaT cells were used. The anti-inflammatory characteristics of CHR were analyzed using the Psoriasis Area Severity Index (PASI), immunohistochemistry, immunofluorescence, and flow cytometry. Furthermore, transcriptome sequencing, immunoblotting, and qRT-PCR were applied to investigate how CHR regulates psoriasis at the molecular level. RESULTS: In our research, we found that topical CHR administration significantly alleviated IMQ-induced psoriatic manifestations in mice, demonstrating reduced erythema, decreased epidermal thickening, and diminished scaling. Histopathological improvements correlated with lower PASI scores and reduced splenomegaly. CHR restrained excessive activation of Th1/Th17 cells, inhibited keratinocyte hyperproliferation and blunted inflammatory responses, accompanied by decreased phosphorylation of AKT and p65. CONCLUSION: CHR exerts robust anti-psoriatic effects by suppressing keratinocyte over-proliferation and restoring Th1/Th17 immune homeostasis. Our data reveal a correlation between CHR intervention and suppressed AKT/NF-κB signaling activation, suggesting CHR may serve as a potential candidate for psoriasis treatment.