Background/Purpose: Gout is caused by the inflammation induced from the precipitation of monosodium urate (MSU) crystals in joints and is the most common inflammatory arthritis in the United States, occurring mostly in males and in up to 4% of the population. Since high levels of systemic uric acid and inflammation are both contributors to this chronic inflammatory condition, the pharmacological armamentarium includes both urate-lowering and anti-inflammatory therapeutic regimens. In adjunct to drugs to reduce inflammation, natural methods including dietary modifications and supplementation with nutraceutical compounds known to reduce inflammation have demonstrated some success in previous studies. In agreement, we have previously shown that cherry juice can reduce the incidence of flares in gout patients and significantly suppress IL-1β secretion in vitro in human cells. The objective of this study was to establish the anti-inflammatory influence of cherry juice in a murine model of gout to create a model experimental platform to use in future work investigating the molecular mechanism suppressing inflammation.

Methods:

Cherry juice concentrate was administered daily by oral gavage (240 µL/kg) to commercially available BALB/C-Tg(NFκB-RE-luc)-Xen mice that harbor a firefly luciferase cDNA reporter under the regulation of 3 NFκB responsive elements. After 14 days, gouty inflammation was induced by intra-articular injection of monosodium urate (MSU) crystals (0.5 mg) into the tibio-tarsal joint (ankle) under anesthesia. NFκB activity was measured locally in the injected ankle using the Xenogen in vivo imaging system (IVIS 200) and decalcified feet/ankles were paraffin-embedded and stained by H&E for histopathological analysis.

Results: Oral administration of cherry juice concentrate significantly reduced NFκB activity in mouse feet/ankles by IVIS analysis relative to control mice treated with PBS. Bioluminescent imaging signals correlating to NFκB activation and measured by total photon counts were inhibited almost 2-fold with the entire foot used as the region of interest in the analysis. Furthermore, histopathology by H&E showed a suppression of infiltrates into the space of the tibio-tarsal joint in mice receiving cherry juice concentrate when compared to PBS-treated control counterparts.

Conclusion:

The results of this study demonstrate a significant inhibition of inflammation, as measured by histology and NFκB activity, in the joint space of mice injected with MSU to induce gout; thereby recapitulating the conclusions of our previous work in human cells and gout patients and establishing a viable mouse model to use in future experiments delineating the molecular mechanism of this immunosuppressive response. Near future experiments include a comprehensive analysis of proinflammatory cytokines in the serum of these mice and long-term work will include in vitro assays investigating the effects of cherry juice concentrate on oxidative burst and IL-1β secretion following inflammasome activation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/orally-administered-cherry-juice-inhibits-localized-nf%ce%bab-activity-and-histopathological-infiltrates-in-a-murine-model-of-gout/