Kava‐241 reduced periodontal destruction in a collagen antibody primed Porphyromonas gingivalis model of periodontitis

Abstract

Aim The aim of this study was to evaluate the effect of Kava-241, an optimized Piper methysticum Kava compound, on periodontal destruction in a collagen antibody primed oral gavage model of periodontitis. Methods Experimental periodontitis was induced by oral gavage of Porphyromonas gingivalis (P.gingivalis) + type-II collagen antibody (AB) in mice during 15 days. Mice were treated with Kava-241 concomitantly or prior to P.gingivalis gavage and compared to untreated mice. Comprehensive histomorphometric analyses were performed. Results Oral gavage with P.gingivalis induced mild epithelial downgrowth and alveolar bone loss while oral gavage with additional AB priming had greater tissular destruction in comparison to gavage alone (p<0.05). Kava-241 treatment significantly (p<0.05) reduced epithelial downgrowth (72%) and alveolar bone loss (36%) in P.gingivalis+AB group. This Kava-241 effect was associated to a reduction of inflammatory cells counts within soft tissues and an increase of fibroblasts (p<0.05). Conclusion Priming with type-II collagen antibody with oral gavage is a fast and reproducible model of periodontal destruction adequate for the evaluation of novel therapeutics. The effect of Kava-241 shows promise in the prevention and treatment of inflammation and alveolar bone loss associated with periodontitis. Further experiments are required to determine molecular pathways targeted by this therapeutic agent.

Akkermansia muciniphila reduces Porphyromonas gingivalis‐induced inflammation and periodontal bone destruction

“…Periodontitis could be considered the consequence of a host‐mediated disruption of microbial homoeostasis (Bartold & Van Dyke, ). Therefore, new therapeutic strategies aim to control the inflammatory response and restore the balance between pro‐ and anti‐inflammatory cytokines through the use of several drugs or active compounds (Alshammari et al, ; Morand et al, ). However, the risk of side effects alleviates their systemic use and reinforces the need for new therapeutic tools.…”

“…Ligatures were replaced 3 times/week during 3 weeks with fresh P. gingivalis ‐soaked ligatures. On days in between ligature placement, oral gavage with P. gingivalis (5 × 10 8 CFU) was provided as previously described (Alshammari et al, ). After 3 weeks of periodontitis induction, therapeutic inoculation of A. muciniphila (10 9 cells) was administrated by daily gavage concomitantly with P. gingivalis for two additional weeks.…”

“…The palatal bones were treated with 10% bleach for 1 min, washed with PBS three times for 5 min and then dried at 37°C. Bone staining was performed at room temperature with 1% methylene blue (Sigma‐Aldrich) for 1 min, after which specimens were washed and dried 30 min at 37°C (Alshammari et al, ). Bone loss was defined as the distance between cemento‐enamel junction (CEJ) and the most coronal alveolar bone.…”

“…Following euthanasia, the right side of the palatal bone and intact surrounding tissue were fixed with 4% freshly prepared paraformaldehyde (Sigma‐Aldrich) in PBS (pH 7.2) for 24h at 4°C. Following fixation, specimens were decalcified and embedded for cryostat sectioning as previously described (Alshammari et al, ). A minimum of 6 fields from each inter‐dental area (from CEJ to root apex of the second molar) was analysed, and inflammatory scoring and osteoclast scoring were performed (see Appendix ) (Alshammari et al, ).…”

Reduction of Articular and Systemic Inflammation by Kava-241 in a Porphyromonas gingivalis-Induced Arthritis Murine Model

“…Due to its potential toxicity, optimized compounds have been developed with interesting results regarding prevention or management of inflammation (20). Recently, we demonstrated that Kava-241, a synthetic kava analog, reduced TNF-␣ secretion in Escherichia coli lipopolysaccharide (LPS)-stimulated RAW cells but also prevented alveolar bone loss and inflammation associated with P. gingivalis-induced PD in a collagen antibody-primed mouse model (21).…”