Abstract
Several recent studies have documented that supplementation with pomegranate fruit extract inhibits inflammatory symptoms in vivo. However, the molecular basis of the observed effects has not been fully revealed. Although previous studies have documented the inhibition of nitric oxide and cyclooxygenase (COX) activity in vitro by plant and fruit extracts added directly into the culture medium but whether concentrations of bioactive compounds sufficient enough to exert such inhibitory effects in vivo can be achieved through oral consumption has not been reported. In the present study we determined the effect of rabbit plasma obtained after ingestion of a polyphenol rich extract of pomegranate fruit (PFE) on COX enzyme activity ex vivo and the IL-1β-induced production of NO and PGE2 in chondrocytes in vitro. Plasma samples collected before and 2 hr after supplementation with PFE were tested. Plasma samples collected after oral ingestion of PFE were found to inhibit the IL-1β-induced PGE2 and NO production in chondrocytes. These same plasma samples also inhibited both COX-1 and COX-2 enzyme activity ex vivo but the effect was more pronounced on the enzyme activity of COX-2 enzyme. Taken together these results provide additional evidence of the bioavailability and bioactivity of compounds present in pomegranate fruit after oral ingestion. Furthermore, these studies suggest that PFE-derived bioavailable compounds may exert an anti-inflammatory effect by inhibiting the inflammatory cytokine-induced production of PGE2 and NO in vivo.
Highlights
Pomegranate has been used for centuries to confer health benefits in a number of inflammatory diseases
The HPLC chromatogram of the pomegranate fruit extract (PFE) used in this study showed the presence of several polyphenols including ellagic acid (EA)
For the HPLC analyses ellagic acid was used as a marker since EA has been shown to become bioavailable after oral consumption of pomegranate juice and the presence of EA in blood and urine has been suggested as a reliable marker for assessing compliance in studies involving the consumption of pomegranate fruit [35]
Summary
Pomegranate has been used for centuries to confer health benefits in a number of inflammatory diseases. Several groups have reported that consumption of pomegranate may have cholesterol lowering and cardiovascular and other chronic diseases preventing effects in vivo [8,9,10,11] In these studies the major effect of the pomegranate extract consumption was the reduction of oxidative stress, inhibition of p38-mitogen-activated protein kinase (p38MAPK) pathway and inhibition of the activation of transcription factor NF-κB. Activation of p38-MAPK and NFκB is intimately associated with the increased gene expression of TNF-α, IL-1β, MCP1, iNOS and COX-2-agents that are critical mediators of inflammation and the pathogenesis of inflammatory and degenerative joint diseases [12,13] These and other published studies [[14], reviewed in [15,16]] demonstrate that PFE possesses strong antioxidant and anti-inflammatory properties and its consumption has the potential to prevent diseases in which redox imbalance and inflammatory stimuli plays a decisive role
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