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.