Fractionation of polyphenol-enriched apple juice extracts to identify constituents with cancer chemopreventive potential

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Apples and apple juices are widely consumed and rich sources of phytochemicals. The aim of the present study was to determine which apple constituents contribute to potential chemopreventive activities, using a bioactivity-directed approach. A polyphenol-enriched apple juice extract was fractionated by various techniques. Extract and fractions were tested in a series of test systems indicative of cancer preventive potential. These test systems measured antioxidant effects, modulation of carcinogen metabolism, anti-inflammatory and antihormonal activities, and antiproliferative potential. Regression analyses indicated that 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging potential correlated with the sum of low molecular weight (LMW) antioxidants (including chlorogenic acid, flavan-3-ols, and flavonols) and procyanidins, whereas peroxyl radicals were more effectively scavenged by LMW compounds than by procyanidins. Quercetin aglycone was identified as a potent Cyp1A inhibitor, whereas phloretin and (-)-epicatechin were the most potent cyclooxygenase 1 (Cox-1) inhibitors. Aromatase and Cyp1A inhibitory potential and cytotoxicity toward HCT116 colon cancer cells increased with increasing content in procyanidins. Overall, apple juice constituents belonging to different structural classes have distinct profiles of biological activity in these in vitro test systems. Since carcinogenesis is a complex process, combination of compounds with complementary activities may lead to enhanced preventive effects.

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