Efficacy of gigantol, a bibenzyl compound, against Porphyromonas gingivalis

This study aims to investigate the inhibitory effect of gigantol against P. gingivalis. The effect of gigantol against the planktonic culture of P. gingivalis was determined by broth microdilution and CFU assay. In addition, bacterial cell surface hydrophobicity and aggregation were elucidated. Confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) were performed to observe biofilm thickness and the biofilm structure, respectively. The gingipain-related genes were evaluated using qPCR. Moreover, molecular docking analysis has also detected the interaction between gigantol and gingipains. Finally, the cytotoxicity effect of gigantol on human gingival fibroblasts (HGFs) was also observed by MTT assay. The MIC and MBC of gigantol against planktonic P. gingivalis were 0.312 mg/mL. The findings indicated that the effect of gigantol at sub-MIC concentrations can also suppress bacterial growth. Additionally, this compound increased cell surface hydrophobicity and aggregation. CLSM images demonstrated its inhibitory effect on the pre-formed biofilm of P. gingivalis. SEM exhibited that gigantol could affect the bacterial membrane. The downregulation of gingipain-related gene expression was observed. Moreover, molecular docking showed that this compound blocks Kpg and RgpB proteases. Furthermore, the cytotoxicity of gigantol on HGFs exhibited less toxicity than 0.12% CHX. Our findings indicated that gigantol inhibits the P. gingivalis biofilm and establishment, which may lead to a potential therapeutic compound for periodontitis patients.