Identification of potentially cytotoxic phenolics present in pomegranates (Punica granatum L.)

Abstract Recent research into the benefits of feeding pomegranate ( Punica granatum L.) peels or extracts to dairy cattle has suggested these supplements may increase the health and productivity of these animals. However, in Victoria, Australia, several cattle died after consuming large amounts of pomegranate fruit, causing suspicion about the safety of pomegranates to cattle. An in vitro bioassay mediated approach was used to purify and identify metabolites from a crude extract of pomegranate fruit obtained from the affected farm. The metabolites that are most likely to cause cytotoxicity to bovine kidney epithelial cells (MDBK) were identified as gallic acid (IC 50 41.2 ± 19.0 µg/mL), ellagic acid, and punicalagin (IC 50 314.1 ± 110.7 µg/mL). Although only small concentrations of gallic acid (8 µg/mg dried extract) were detected in the pomegranate fruit extract, microbial metabolism of punicalagin (276.2 µg/mg dried extract) in the rumen could result in the formation of substantial amounts of gallic acid, potentially contributing to significant toxicity.