Paeoniflorin as a potential agent for urticaria treatment: Suppressing mast cell degranulation through HMGB1/TLR4/NF-κB signaling inhibition.

INTRODUCTION

Paeoniflorin (PF) has strong immunomodulatory effects and has been widely used in the treatment of many diseases, but its mechanism of action in urticaria is not clear. The aim of this experiment was to investigate the role and mechanism of paeoniflorin in improving mast cell degranulation in urticaria.

METHODS

The mouse model of urticaria was replicated by ovalbumin+ aluminum hydroxide method, and the mast cell degranulation model was induced by anti-DNP IgE+ Dinitrophenyl- Bovine Serum Albumin (DNP-BSA), and the mice and cells were intervened by different doses of PF. The histopathological changes of the dorsal skin were observed using hematoxylin-eosin (HE) staining, the infiltration of mast cells was observed by Toluidine blue staining, the expression of mast cell tryptase (MCT) was examined by Immunohistochemical staining, the cell viability was detected by CCK8 assay, and Rhod-2/AM flow cytometry assay to determine calcium ion content, enzyme-linked immunosorbent assay (ELISA) detected mast cell degranulation-associated factors, and Western blot analyzed HMGB1/TLR4/NF-κB signaling factors.

RESULTS

PF reduced the number of scratches in mice, ameliorated histopathological damage in dorsal skin, decreased mast cell degranulation rate, reduced the levels of Ca, MCT, β-HEX, HIS, MCP-1, TNF-α, and IL-13, and inhibited the expression of HMGB1, TLR4, MyD88, NF-κB p65 (Nucleus), and p-IκBα. Moreover, Rec-HMGB1 reversed the effect of PF.

CONCLUSION

PF mitigates urticarial mast cell degranulation through the inhibition of the HMGB1/TLR4/NF-κB signaling pathway, suggesting its potential as a therapeutic agent for the treatment of urticaria.