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Seaweed Gracilaria vermiculophylla Papenfuss, commonly called as ‘Worm wart weed’, is a red alga widely distributed in the coastal areas of several countries. Though G. vermiculophylla has been reported to have antioxidant and anti-inflammatory effects, such effects on periodontal diseases remain unclear. In this study, we investigated the anti-inflammatory effects of G. vermiculophylla on the production of inflammatory cytokines in Porphyromonas gingivalis induced RAW 264.7 cells. Gracilaria vermiculophylla on that RAW 264.7 cells had no cytotoxic effect on cell viability compared with untreated controls. In P. gingivalis stimulated RAW 264.7 cells, G. vermiculophylla treatment reduced nitric oxide (NO) levels in a concentration-dependent manner by downregulating inducible nitric oxide synthase (iNOS) proteins. Reverse transcription-quantitative (RT-q) PCR inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α mRNA. Western blot analysis found that both inhibitor of kappa B alpha (IκBα) kinase (IKK) phosphorylation and IκBα degradation in P. gingivalis stimulated RAW 264.7 cells was inhibited by G. vermiculophylla in a dose-dependent manner. In addition, G. vermiculophylla treatment reduced the nuclear translocation of nuclear factor (NF)-κB p65, suggesting that the anti-inflammatory effect of G. vermiculophylla is associated with the inhibition of NF-κB signaling pathways. Overall, the findings indicate that the red alga Gracilaria vermiculophylla extract may have anti-inflammatory effects on periodontitis and can serve as a potent therapeutic agent to prevent periodontal disease. [ABSTRACT FROM AUTHOR]