Investigation of the abilities of cannabinoids to alter biomarker production involved in inflammation and periodontal tissue regeneration

Periodontitis is a self-destructive, long-standing inflammation condition which has serious repercussions on general health and oral health, in particular. Periodontitis is caused by an immune response of periodontal cells with the noxious gram-negative bacteria. The chronic interaction between the immune cells, periodontal cells and bacterial virulence factors results in expression of cytokine cascade. It can result in destruction of periodontal apparatus which, includes the gingival recession and alveolar bone destruction: leading to periodontal pocket formation and could eventually lead to loss of tooth. Various treatment methods are available but still there is a need for robust treatment for periodontitis due to limitations and side effects of the available treatment methods. Cannabinoids have been proven to possess anti-inflammatory potential and antimicrobial capacity and hence could be found promising to address chronic diseases such as periodontitis. The aim of the present study is to evaluate the role of cannabinoids such as CBD and CBG to limit the over expression of self-destructive inflammatory cytokines in an in-vitro periodontitis model. This in-vitro periodontitis model comprises cells (Cell lines and primary cells) and inflammatory agents (LPS and Flagellin). In order to evaluate the efficacy of cannabinoids for their anti-inflammatory potential, Cell lines and primary cells were pre-treated with cannabinoids before presenting them with inflammatory stimulus such as LPS and Flagellin. The methods used include using different concentrations of CBD, CBG, A-251 and O-1602 therefore, the toxicity of these compounds was evaluated on the cells used in the study. The efficacy of the cannabinoids to modulate the release of cytokines such as IL-8, IL-6, IL-1β and TNF-α was evaluated both at mRNA level and protein level. The results obtained showed that CBD was cytotoxic at concentration 100 µM but not cytotoxic at concentrations below 10 µM on the cells used in this project. CBG, A-251 and O-1602 were not found to be cytotoxic for the concentration well above that used in the project. CBD and CBG were shown to modulate the expression and production of pro-inflammatory cytokines induced by LPS/flagellin; pre-exposure with CBD decreased the expression of IL-8 by 325 times at mRNA and by 60-70 % at protein level on TIGK cells. Whereas, pre-exposure with CBD decreased the expression of IL-8 approximately 60 % at m-RNA level and 25 % at protein level on primary periodontal cells. This study demonstrated the ability of cannabinoids to determine immunomodulatory effects suggesting possible therapeutic applications in the field of periodontal research.