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

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 a collagen antibody cocktail (CIA) to induce joint inflammation and tissular destruction. Clinical inflammation score and radiological analyses of the paws were performed continuously, while histological assessment was obtained at sacrifice. Mice exposed to P. gingivalis and a CIA cocktail and treated concomitantly with Kava-241 exhibited a reduced clinical inflammatory score and a decreased number of inflammatory cells and osteoclasts within joint. Kava-241 treatment also decreased significantly tumor necrosis factor alpha (TNF-α) in serum from mice injected with a Toll-like receptor 2 or 4 (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 mitogen-activated protein kinase (MAPK)-related signal elements, and reduced LPS-induced TNF-α factor (LITAF), all explaining the observed reduction of TNF-α secretion. Taken together, these results emphasized the novel properties of Kava-241 in the management of inflammatory conditions, especially TNF-α-related diseases such as infective RA.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Huck O,You J,Han X,Cai B,Panek J,Amar S

doi

10.1128/IAI.00356-18

subject

Has Abstract

pub_date

2018-08-22 00:00:00

issue

9

eissn

0019-9567

issn

1098-5522

pii

IAI.00356-18

journal_volume

86

pub_type

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