Numerous studies have demonstrated the effectiveness of targeting HMGB1 as an anti-inflammatory strategy, showing that inhibiting HMGB1 can significantly reduce inflammatory responses in myocarditis, sepsis, periodontitis, and other diseases by down-regulating inflammatory cytokines such as IL-1β, TNF-α, and IL-6 (Yang H. et al., 2019; Jiang et al., 2021; Luo et al., 2022; Yang et al., 2022). This evidence concerns the gene TNF and periodontitis.