P4–260: Neuroprotective effects of pomegranate juice extracts on quinolinic acid–induced excitotoxicity in human neurons

Abstract

Background: Quinolinic acid (QUIN) excitotoxicity is mediated by elevated intracellular Ca2+ levels, and nitric oxide (NO•) mediated oxidative stress resulting in DNA damage, PARP activation, NAD+ depletion and cell death. Methods:We evaluated the effect of a series of pomegranate juice extracts (i.e. helow, malasi, qusum, and hamedh) with antioxidant properties on QUIN induced excitotoxicity on primary cultures of human neurons. Results: We showed that helow and malasi can attenuate QUIN-induced excitotoxicity to a greater extent than qusum and hamedh. Similarly, both helow and malasi were able to attenuate QUIN-induced Ca2+ influx and nNOS activity to a greater extent compared to qusum, and hamedh. All extracts reduced the oxidative effects of increased NO• production thereby reducing the formation of 3-nitrotyrosine and PARP activity, and hence preventing NAD+ depletion and cell death. Conclusions: In addition to the well-known antioxidant properties of these natural phytochemicals, the inhibitory effect of some of these compounds on specific excitotoxic processes such as calcium influx provides additional evidence for the beneficial health effects of pomegranate juice extracts in excitable tissue, particularly within the CNS.