Bomidin prevents inflammatory responses in macrophages by inhibiting toll-like receptor 4/nuclear factor-κB activation and blocking metabolic reprogramming to alleviate periodontal inflammation.

Macrophages play an important role in the pathogenesis and prognosis of periodontitis, a complex immune-inflammatory disease that causes gingival inflammation and alveolar bone loss. Bomidin, a novel recombinant antimicrobial peptide known for its potent antibacterial properties, holds promising potential in the field of anti-inflammation. Hence, the research aimed to investigate the anti-inflammatory properties of bomidin in RAW 264.7 cells and related underlying mechanisms. Herein, bomidin and Porphyromonas gingivalis (Pg)-lipopolysaccharide (LPS) were administered both simultaneously and separately to RAW 264.7 cells. Notably, bomidin neutralized LPS in vitro, effectively reducing pro-inflammatory cytokines release in LPS-activated macrophages. Additionally, bomidin could bind to toll-like receptor (TLR)4 and suppress the activation of TLR4/nuclear factor-κB pathway. Consequently, this inhibition results in a reduction in both the expression and secretion of pro-inflammatory mediators, as well as a decrease in nitric oxide production and the occurrence of late-stage apoptosis in macrophages. Furthermore, bomidin induced the pro-to-anti-inflammatory phenotype switch via hypoxia-inducible factor-1α and downregulated the glycolysis level. In vivo, bomidin markedly alleviated periodontal inflammation symptoms, inhibited activated macrophages, improved inflammatory cell infiltration, and enhanced the healing of mucosa in mice. Altogether, the findings of this study identify bomidin as a highly promising therapeutic approach for managing periodontal inflammation and effectively improving its inflammatory manifestations.