Efficacy of Xiao-Feng Powder-loaded thermosensitive composite hydrogel alleviates allergic contact dermatitis by targeting Complement factor B

Background Allergic contact dermatitis (ACD) is an immunological disorder elicited by antigen exposure, which activates the immune system and leads to T cell-mediated inflammation. Purpose This study aimed to investigate the role of TCM-loaded thermosensitive composite hydrogel in alleviating ACD and elucidated its underlying mechanisms in HaCaT cell induced by TNFα/IFNγ. Methods SADBE-induced ACD mouse and TNFα/IFNγ-induced damage to HaCaT cells were established. CFB expression was knocked down in HaCaT cells via shRNA plasmid transfection. UPLC-MS was employed to analyze the chemical composition of the TCM compound XFP. The composite F127-PEG200/XFP@SA-GEL-PVP was prepared by encapsulating XFP in microspheres via a blend of sodium alginate (SA), gelatin (GEL), and polyvinylpyrrolidone (PVP), followed by their integration into a hydrogel matrix of Pluronic F127 (F127) and PEG200. Scratching behavior, skin fold thickness, spleen-thymus index, histological analysis, photoacoustic imaging system was used to evaluated the effect of F127-PEG200/XFP@SA-GEL-PVP. Finally, expression levels of CFB, RANKL, IL4, IL13, TSLP, and IL25 were analyzed by immunohistochemistry and western blot. Results CFB regulates Th2-type cytokine expression via C3 in the TNFα/IFNγ-induced HaCaT cells. F127-PEG200/XFP@SA-GEL-PVP exhibited stable physicochemical properties and favorable biocompatibility. Treatment with F127-PEG200/XFP@SA-GEL-PVP significantly reduced scratching behavior, skin fold thickening, and inflammatory infiltration in ACD mice, inhibited mast cell degranulation, restored vascular morphology and local blood flow in skin and spleen tissues, and downregulated the expression levels of Th2-type cytokines (IL4, IL13, TSLP) and pro-inflammatory mediators (CFB, RANKL, IL25). Conclusion These findings demonstrate that F127-PEG200/XFP@SA-GEL-PVP exerts protective effects in ACD. Silencing CFB restored HaCaT cell viability after TNFα/IFNγ treatment and the modulation of the C3 pathway reduced Th2-type cytokine expression.