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Bioavailable constituents/metabolites of pomegranate (Punica granatum L) preferentially inhibit COX2 activity ex vivo and IL-1beta-induced PGE2 production in human chondrocytes in vitro

Meenakshi Shukla1, Kalpana Gupta1, Zafar Rasheed1*, Khursheed A Khan2 and Tariq M Haqqi13*

Author Affiliations

1 Division of Rheumatic Diseases, Department of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA

2 Department of Kulliyat, Faculty of Unani Medicine, Aligarh Muslim University, Aligarh 202 002, India

3 Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, 6439 Garners Ferry Road, Columbia, SC 29209, USA

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Journal of Inflammation 2008, 5:9  doi:10.1186/1476-9255-5-9

Published: 13 June 2008


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.