BACKGROUND

Psoriasis is a common chronic immune-inflammatory skin disease that remains a challenge to treat. Benzoylpaeoniflorin (BPF) is a monoterpenoid glycoside derived from the roots of Paeonia albiflora Pall., a plant in the peony family (Paeoniaceae). It has shown promising anti-inflammatory effects. However, its therapeutic efficacy in psoriasis has not yet been investigated. This study aims to evaluate the therapeutic effects of BPF in Imiquimod (IMQ)-induced psoriasis-like lesions and to elucidate its underlying mechanisms.

METHODS

The psoriasis-like model was established in SKH-1 mice using IMQ to evaluate the in vivo efficacy of BPF. Flow cytometry was employed to analyze the proportions of immune cells in the spleen and peripheral blood of the mice. RNA-sequencing was used to screen the differentially expressed genes and key signaling pathways in BPF-treated mice. Molecular docking was used to simulate the binding mode of BPF and potential targets. The human keratinocytes cells (HaCaT) and bone marrow-derived dendritic cells (BMDCs) were used to assess the inhibitory effects of BPF on cell proliferation, cell maturation and the activation of the TNF-α/NF-κB signaling pathway.

RESULTS

BPF improved the clinical symptoms and histological features of psoriasis-like lesions in IMQ-treated SKH-1 mice. BPF reduced the proportions of lymphocytes and dendritic cells (DCs), modulated the ratio of Th17/Treg cells and promoted immune balance restoration. RNA-sequencing analysis showed that BPF ameliorated psoriasis by modulating multiple immune-related and cytokine-associated signaling pathways, including the NF-κB, TNF-α, and IL-17 signaling pathways. Molecular docking demonstrated that BPF may play an anti-psoriasis role by interfering with the formation of TNF-α trimer and binding TNF-α to TNF-R. BPF inhibited TNF-α-induced proliferation of HaCaT cells and maturation of DCs, as well as TNF-α-induced activation of NF-κB and secretion of inflammatory cytokines.

CONCLUSIONS

BPF alleviates psoriasis-like inflammation through multiple mechanisms, offering new insights into potential therapeutic strategies.