Cinnamaldehyde protects against ligature-induced periodontitis through the inhibition of microbial accumulation and inflammatory responses of host immune cells

Cinnamaldehyde (CA), the main active ingredient in cinnamon, has been proved to be a potential candidate for controlling inflammation; however, there has been little evidence demonstrating its role in alleviating periodontitis. The aim of this study was to investigate the effect of orally administered CA on ligature-induced periodontitis in mice and the administration of CA on the Porphyromonas gingivalis (Pg) supernatant-induced inflammatory responses of murine macrophages and human periodontal ligament cells (HPDLCs). In vivo experiments showed that the oral administration of CA significantly inhibited bone resorption, the accumulation of anaerobic bacteria and host immuno-inflammatory responses in ligature-induced periodontitis in mice. In vitro, CA inhibited the expression of Pg supernatant-induced IL6, IL8, TNFA and IL1B and reactive oxygen species in RAW 264.7 and HPDLCs, involving the inactivation of the NFKB signaling pathway, which was activated by the Pg supernatant. Also, the expression of adherent and chemotactic-related cytokines was inhibited by CA, accompanied with a reduction in adherent HPDLCs. Moreover, CA ameliorated the cellular senescence of HPDLCs induced by H₂O₂, together with a decrease in senescence-associated-β-galactosidase positive cells and decrease in the expression of P53, P21 and P16. Furthermore, CA promoted the osteogenic differentiation of HPDLCs with an increase in alkaline phosphatase expression and activity, formation of more mineralization nodules, and increased the expression of bone sialoprotein and osteopontin. Conclusions: Daily diet-added CA may be beneficial for oral health care, especially for the control of periodontic disease by suppressing the dysbiosis of biofilms and inhibiting the immunoinflammatory responses of migrated macrophages and local resident periodontal ligament cells to specific pathogen irritations.