NYMC Faculty Publications

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

Journal Title

Infection and Immunity

First Page

e00356-18

Document Type

Article

Publication Date

September 2018

Department

Pharmacology

Abstract

Rheumatoid arthritis (RA) is an inflammatory disease that has been linked to several risk factors including periodontitis. Identification of new anti-inflammatory compounds to treat arthritis is needed. We had previously demonstrated the beneficial effect of Kava-241, a kavain derived compound, in the management of Porphyromonas gingivalis induced periodontitis. The present study evaluated systemic and articular effects of Kava-241 in an infective arthritis murine model triggered by P.gingivalis bacterial inoculation and primed with collagen antibody cocktail (CIA) to induce joint inflammation and tissular destruction. Clinical inflammation score and radiological analysis of the paws were performed continuously while histological assessment was obtained at sacrifice. Mice exposed to P.gingivalis, CIA cocktail and treated concomitantly with Kava-241 exhibited reduced clinical inflammatory score and decreased number of inflammatory cells and osteoclasts within joint. Kava-241 treatment also decreased significantly TNF-alpha in serum from mice injected with a TLR 2/4 ligand, P.gingivalis.-lipopolysaccharide (LPS). Finally, bone-marrow derived macrophages infected with P.gingivalis and exposed to Kava-241 displayed reduced TLR-2/4, reduced MAPKs related signal elements and reduced LITAF all explaining the observed reduction of TNF-alpha secretion. Taken together, these results emphasized the novel properties of Kava-241 in the management of inflammatory conditions especially TNF-alpha related diseases such as infective RA.

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