Novel therapeutic approach in periodontitis: Sulforaphane attenuates disease progression via Nrf2-mediated antioxidant defense.

Periodontitis, one of the most prevalent global disorders, is characterized by oxidative stress-mediated pathogenesis that leads to progressive tissue destruction and bone loss. Given that nuclear factor erythroid 2-related factor 2 (Nrf2) is essential for cellular antioxidant defense, targeting this pathway may represent a promising therapeutic strategy. Sulforaphane (SFN), a natural isothiocyanate with potent antioxidant properties, has been confirmed to be effective against various oxidative stress-related disorders. This study aimed to investigate whether and how SFN attenuates periodontitis progression through Nrf2-mediated antioxidant defense activation. Our study demonstrated that SFN effectively suppressed inflammatory responses induced by Porphyromonas gingivalis Lipopolysaccharides (P. gingivalis LPS) in human gingival fibroblasts (HGFs) in vitro and attenuated periodontitis progression in an experimental rat model. In HGFs, SFN significantly reduced inflammatory mediator production, decreased intracellular and mitochondrial reactive oxygen species (ROS) accumulation, and restored mitochondrial function. Mechanistically, the anti-inflammatory and antioxidant effects of SFN were Nrf2-dependent, as demonstrated by their abolishment in Nrf2-silenced HGFs and enhancement in Nrf2-overexpressing cells. Additionally, SFN alleviated periodontal tissue damage and reduced inflammation in a periodontitis rat model, accompanied by enhanced antioxidant capacity. These results demonstrate that SFN ameliorates periodontitis by activating Nrf2-dependent antioxidant defense, suggesting its therapeutic potential for periodontal treatment.