Abstract
OBJECTIVE: Although consumption of dietary supplements containing pomegranate extract (POMx) by patients with arthritis is on the rise, the efficacy of such preparations in suppressing joint inflammation and damage is not known. The present study was designed to evaluate a standardized preparation of POMx using collagen-induced arthritis (CIA) in mice, a widely used animal model of rheumatoid arthritis. METHODS: CIA-susceptible DBA/1 mice were fed POMx by gavage before and after immunization with chicken type II collagen. Severity of clinical arthritis was scored using a visual scoring system. Arthritic joints were analyzed by histopathology and graded. Lysates were generated from mouse joints and levels of anti-type II collagen immunoglobulin G and inflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha were quantified by enzyme-linked immunosorbent assay. The effect of POMx on lipopolysaccharide-induced nitric oxide production was determined by Griess reaction and mitogen-activated protein kinase activation was studied by western immunoblotting in mouse macrophages. RESULTS: Consumption of POMx potently delayed the onset and reduced the incidence of CIA in mice. Severity of arthritis was also significantly lower in POMx-fed animals. Histopathology of the arthritic joints from POMx-fed mice demonstrated reduced joint infiltration by the inflammatory cells, and the destruction of bone and cartilage were alleviated. Levels of IL-6 were significantly decreased in the joints of POMx-fed mice with CIA. In mouse macrophages, POMx abrogated multiple signal transduction pathways and downstream mediators implicated in the pathogenesis of rheumatoid arthritis. CONCLUSION: Our studies suggest that inhibition of a spectrum of signal transduction pathways and the downstream pathogenic cellular response by POMx or compounds derived from it may be a useful approach for the prevention of the onset and severity of inflammatory arthritis.