Published: June 09, 2011 r2011 American Chemical Society 7679 dx.doi.org/10.1021/jf200926t | J. Agric. Food Chem. 2011, 59, 7679–7687 ARTICLE pubs.acs.org/JAFC Metabolic Profiling of Strawberry Grape (Vitis  labruscana cv. ‘Isabella’) Components by Nuclear Magnetic Resonance (NMR) and Evaluation of Their Antioxidant and Antiproliferative Properties Severina Pacifico,* Brigida D’Abrosca, Monica Scognamiglio, Marialuisa Gallicchio, Nicoletta Potenza, Simona Piccolella, Aniello Russo, Pietro Monaco, and Antonio Fiorentino Dipartimento di Scienze della Vita, Laboratorio di Fitochimica, Seconda Universit  a degli Studi di Napoli, via Vivaldi 43, I-81100 Caserta, Italy b S Supporting Information ABSTRACT: In the assessment of the antioxidant properties of edible plants, the widely consumed Vitis  labruscana cv. ‘Isabella’, known in Italy as “fragola” (strawberry) grape, was of interest. Phenol and flavonoid contents of the methanolic extracts of peel, pulp, seed, leaf, and stalk components of the plant were determined. The metabolic profile of the extracts was performed by 1D and 2D NMR. Quantitative analysis, obtained in the presence of 0.01% of internal standard trimethylsilyl propionate, evidenced the presence of catechins in both stalk and seed extracts, whereas caffeic acid and quercetin were the main metabolites of the leaf extract. Furthermore, the extracts were tested for their radical scavenging and reducing capacities by measuring their capacity to scavenge DPPH • and ABTS •+ and to reduce Fe(III) and Mo(VI) salts. The antioxidant efficacy of the extracts in cell-free systems and their antiproliferative activity toward HepG2 and A549 cells were also evaluated. Seed and stalk components are able to reduce by 39.6 and 40.6%, respectively, the amount of the metabolically active HepG2 cells after only 24 h of exposure. KEYWORDS: Vitis  labruscana, ‘Isabella’ grape, metabolic profiling, NMR analysis, radical scavenging capacity, antioxidant activity, antiproliferative activity ’ INTRODUCTION It is well-known that an oxidative stress state is a common denominator in the pathogenesis of several chronic diseases. Even the most modern and complex theories on the role of oxidative stress, in physiological and pathological processes, suggest that a balance between production of oxidizing species and antioxi- dant defenses is essential to preserve human health and longevity. Furthermore, a growing number of studies underscore the exis- tence of a constant association between diets based mainly on vegetables and a reduced incidence of chronic illnesses such as proliferative, neurodegenerative, and cardiovascular diseases. 1 Thus, the wide range of antioxidant compounds present in fruits and vegetables appears to play an important beneficial role, con- firmed by both clinical and epidemiological studies. It is currently believed that the combination of micronutrients and nonessential phytochemicals, present in fruits, can play a synergistic role in promoting human health. Several systematic analyses of the nutritional composition of edible fruits have been already carried out, and they primarily focus on the content of antioxidants, 2 micronutrients, and, more recently, polyphenolic compounds. 3,4 As a result, the improvement of the nutritional quality of fruits has become an important objective for strategic and cross-combined biotechnological approaches, relevant both for improving the taste-sensory properties of fruits and for boosting productivity, resistance, and adaptation of fruit plants. In recent decades, targeted searches have been conducted on specific fruits that show an important nutritional value. 5,6 The grape (Vitis vinifera L.) is one of the most commonly consumed fruits, in both fresh and processed form. The economic impact of commercial wine production makes the grape the most studied fruit, under agronomic, genomic, and nutritional perspectives. The high health benefits of grapes have been related to a high content of phenolic compounds, many of which show high antioxidant properties in vitro. Little is known about the phytochemical composition of strawberry grape (Vitis  labruscana cv. ‘Isabella’), a grape with sweet and small berries that was introduced into Europe from America around the end of 1800 when the phylloxera began to spread and compromise the excellence of Italian vineyards. The grape variety, resistant to the aphid, was used as rootstock to save Italian vineyards from attack of the parasite. Italian law 460 permits strawberry grapes to be grown only for use as table grapes or for making wine used for home consumption, with the obligation to grub up the vineyards that exceed the extension request. Recently, an HPLC-DAD-ESI-MS n study of the most important low molecular weight phenolic compounds in hybrid grape cultivar Isabel (Vitis labrusca  Vitis vinifera) red table wines (anthocyanins, pyranoanthocyanins, flavonols, and hydro- xycinnamic acid derivatives) was performed to look for differ- ences between these and V. vinifera red wines. 7 The assessment of anthocyanins content in ‘Isabel' grape showed that the pigments were low when compared to other fruits. 8 In this study, we investigated the phenols and flavonoids content and antioxidant properties of Vitis  labruscana components Received: March 8, 2011 Revised: June 9, 2011 Accepted: June 9, 2011