Naringenin ameliorates swine pulpitis by modulating immune response

Preserving dental pulp vitality is crucial for maintaining the physiological function of the tooth. Naringenin (Nar), known for its immunomodulatory properties, has shown pharmacological effects on various inflammatory diseases. This study aimed to investigate the therapeutic potential of Nar in treating Porphyromonas gingivalis lipopolysaccharide (P.g-LPS)-induced pulpitis in a swine model and to elucidate the mechanisms underlying its therapeutic efficacy. Swine premolars with P.g-LPS-induced pulpitis were divided into four groups: sham, hydrogel, iRoot BP PLUS, and Nar hydrogel. Treatment outcomes were evaluated by assessing neutrophil infiltration, dentin-like tissue regeneration, and coronal pulp tissue preservation using histological and immunohistochemical techniques. To further examine potential cellular responses, the effects of Nar were studied in human dental pulp fibroblasts (hDPFs), human peripheral blood-derived neutrophils (hNeu.), and differentiated HL-60 cells (dHL-60). Surface markers were analyzed using fluorescence-activated cell sorting (FACS), cytokine levels were measured by ELISA, and mineralization was assessed using alkaline phosphatase and Alizarin Red S staining. Neutrophil phagocytosis, bactericidal activity, intracellular reactive oxygen species (ROS) levels, and translocation of transcription factor EB (TFEB)-mediated lysosomal activity were evaluated. Statistical analyses included Shapiro-Wilk test and one-way ANOVA or Kruskal-Wallis test with appropriate post hoc comparisons. The sham group showed severe pulp tissue necrosis and an intense inflammatory response. Hydrogel alone exhibited limited therapeutic effects. Both Nar hydrogel and iRoot BP PLUS promoted dentin-like tissue formation; however, Nar hydrogel reduced inflammatory infiltration and preserved a greater proportion of coronal pulp tissue. In vitro, Nar reduced inflammatory cytokine secretion from hDPFs and neutrophils and improved P.g-LPS-impaired mineralization capacity in hDPFs. Nar also enhanced the phagocytic and bactericidal activities of dHL-60 cells, accompanied by controlled ROS elevation and increased TFEB-mediated lysosomal activity. Nar demonstrates therapeutic potential for pulpitis management by modulating inflammation and promoting dentin-like tissue regeneration. Its efficacy likely stems from the fine-tuning of inflammatory responses. These findings suggest that Nar may represent a potential biological alternative to conventional pulp capping materials for vital pulp therapy.