Protective Effects of 5-(3,4-Dihydroxylphenyl)-γ-valerolactone, a major Metabolite of Cocoa Procyanidins, on Hydrogen Peroxide-induced Apoptosis in Primary Cortical Neurons

Abstract

Procyanidins are the most abundant phytochemicals in the dietary food and responsible for the health effects of cocoa. However due to low absorption of procyanidins, recently researchers are focusing on the simple metabolites of cocoa that are catalyzed by intestinal microbiota and exert health effects. The aim of this study is to figure out the neuroprotective effect of 5-(3,4-Dihydroxyphenyl)-γ-valerolactone (DHPV), a min metabolite of cocoa procyanidins, against hydrogen peroxide-induced oxidative stress in primary cortical neurons. Oxidative stress is strongly associated with many diseases such as neurodegenerative disorders, cancers and cardiovascular diseases and oxidative stress is induced by reactive oxygen species such as hydrogen peroxide (H2O2). In this study, I identified the protective effects of DHPV on oxidative neuronal death. Results showed that H2O2-induced nuclear condensation in apoptotic neurons was inhibited by pre-treatment with DHPV. Pre-treatment with DHPV prevented the H2O2-induced decrease of anti-apoptotic protein, Bcl-2 and inhibited H2O2-induced cleavage of caspase-3 and poly(ADP-ribose) polymerase. I also found that DHPV induced the expression of NADPH:quinone oxidoreductase 1 (NQO1) and enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), a principal antioxidant transcription factor in neuronal cells, demonstrating that DHPV protects neurons from H2O2-induced apoptosis by up-regulation of phaseⅡ antioxidant enzymes.