Daisaikoto restores mitochondrial function and suppresses inflammation induced by periodontal bacteria-derived lipopolysaccharides.

BACKGROUND/PURPOSE: Periodontal disease affects approximately half of the world's population and is the leading cause of tooth loss. This study aimed to identify effective drug candidates for mitigating oral inflammation induced by Porphyromonas gingivalis lipopolysaccharide (P. g LPS), a major virulence factor of periodontal pathogens. We investigated daisaikoto (DST), known for its anti-inflammatory properties in various tissues, and compared its efficacy with shosaikoto (SSK) and hainosankyuto (HNST), both reported to have beneficial effects against periodontitis. MATERIALS AND METHODS: Human periodontal ligament fibroblasts were treated with DST, SSK, HNST, and their active components before and after P. g LPS stimulation. Anti-inflammatory effects were evaluated by quantifying IL-6, COX2, and PGES2 gene expression using qPCR. Mitochondrial function was assessed via measurements of mitochondrial membrane potential (Ψm), Fe2+ content (mtFe2+), and reactive oxygen species (mtROS). In addition, ATP production and glycolytic gene expression were analyzed. RESULTS: DST markedly suppressed IL-6 and PGES2 expression more effectively than SSK and inhibited IL-6 more strongly than HNST. P. g LPS elevated mtROS and mtFe2+ levels while reducing Ψm; these mitochondrial impairments were reversed exclusively by DST. Moreover, DST restored ATP production diminished by P. g LPS exposure. CONCLUSION: DST exhibits superior anti-inflammatory activity compared with SSK and HNST and uniquely reverses mitochondrial dysfunction caused by P. g LPS. Given the association between mitochondrial dysfunction, diabetes, and periodontal disease progression, DST emerges as a promising therapeutic candidate for periodontitis.