Lenabasum Reduces Porphyromonas gingivalis –Driven Inflammation

The aim of this study was to evaluate the potential anti-inflammatory and anti-resorptive effects of lenabasum in the context of Porphyromonas gingivalis ( Pg )–induced inflammation. Lenabasum or ajulemic acid (1′,1′-dimethylheptyl-THC-11-oic-acid), a synthetic analog of THC‐11‐oic acid, has already demonstrated anti-inflammatory properties for the treatment of several inflammatory diseases. In vitro , the cytocompatibility of lenabasum was evaluated in human oral epithelial cells (EC), oral fibroblasts and osteoblasts by metabolic activity assay. The effect of lenabasum (5 µM) treatment of Pg -LPS- and P. gingivalis –infected EC on the pro- and anti-inflammatory markers was studied through RTqPCR. In vivo , lenabasum was injected subcutaneously in a P. gingivalis –induced calvarial abscess mouse model to assess its pro-healing effect. Concentrations of lenabasum up to 5 µM were cytocompatible in all cell types. Treatment of Pg -LPS and Pg -infected EC with lenabasum (5 µM; 6 h) reduced the gene expression of TNF-α, COX-2, NF-κB, and RANKL, whereas it increased the expression of IL-10 and resolvin E1 receptor respectively ( p < 0.05). In vivo , the Pg -elicited inflammatory lesions’ clinical size was significantly reduced by lenabasum injection (30 µM) vs untreated controls (45%) ( p < 0.05). Histomorphometric analysis exhibited improved quantity and quality of bone (with reduced lacunae) and significantly reduced calvarial soft tissue inflammatory score in mice treated with lenabasum ( p < 0.05). Tartrate-resistant acid phosphatase activity assay (TRAP) also demonstrated decreased osteoclastic activity in the treatment group compared to that in the controls. Lenabasum showed promising anti-inflammatory and pro-resolutive properties in the management of Pg -elicited inflammation, and thus, its potential as adjuvant periodontal treatment should be further investigated.