Sulforaphene Mitigates Periodontitis by NRF2‐Dependent Regulation of <i>P. gingivalis</i> ‐Induced Inflammatory Response and Bone Homeostasis

Periodontitis is a prevalent chronic inflammatory disease closely associated with various systemic disorders. Conventional therapies, including mechanical debridement and antibiotics, are often insufficient to fully resolve inflammation or restore bone homeostasis. Sulforaphene (LFS) is abundant in radish seed oil and Lai Fu-zi, a traditional Chinese herbal medicine and has been recognized for its anti-inflammatory potential. Here, we show that LFS markedly attenuates the secretion of pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) from human gingival fibroblasts and inhibits osteoclast differentiation even under IL-1β-induced inflammatory conditions, without compromising the osteogenic capacity of periodontal ligament cells (PDLC). Mechanistically, LFS activates the NRF2 pathway and its protective effect against alveolar bone loss was evident in <i>Nrf2</i> ^+/+ mice but not <i>Nrf2</i> ^-/- mice. Notably, LFS was also found to inhibit the growth, virulence, and biofilm formation of <i>P. gingivalis</i> in vitro, and reduced its abundance within the subgingival microbiota in vivo. Together, these findings identify LFS as a potent NRF2-dependent modulator, offering a promising therapeutic strategy for the prevention and treatment of periodontitis.