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[Display omitted] • Pistacia vera L. shell extract was optimized by a response surface methodology approach. • The HPLC/ESI-MS/MS allowed to identify the main constituents of the optimized extract. • The optimized extract exhibited a significant antioxidant/antiradical activity. • The optimized extract exhibited a notable α-amylase and α-glucosidase inhibitory activity. • Intestinal cell viability (Caco-2, HT29-MTX) was not affected by the optimized extract. Pistacia vera shells, an abundant agricultural by-product, are a rich source of undiscovered bioactive compounds. This study employed a response surface methodology (RSM) approach to optimize the microwave-assisted extraction of antioxidants. The highest total phenolic content, and antioxidant activity were achieved under the optimized extraction conditions (20 % ethanol, 1000 W, 135 s, and solvent-to-solid ratio of 27 mL/g). The resulting extract (OPVS-E) included gallic acid derivatives, hydrolysable tannins, flavonoids, fatty acids, and anacardic acids. Remarkably, OPVS-E displayed potent inhibitory activity against α-amylase (IC 50 = 2.05 μg/mL) and α-glucosidase (IC 50 = 41.07 μg/mL), by far more powerful than the anti-diabetic drug acarbose, OPVS-E exhibited a strong antiradical capacity against reactive oxygen species (ROS) without causing toxicity in intestinal cells (HT29-MTX and Caco-2). These findings introduce OPVS-E as a potential novel dual-action nutraceutical ingredient, able to mitigate postprandial hyperglycemia and counteract the ROS overproduction occurring in type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Abstract: The growing interest in the substitution of synthetic food antioxidants by natural ones has fostered research on vegetable sources and on the screening of raw materials, for identifying new antioxidants. In the present study, an ethanol:water (4:6) extract from Juglans regia leaves was evaluated for its putative in vitro scavenging effects on reactive oxygen species (ROS) [hydroxyl radical (HO ), superoxide radical , peroxyl radical (ROO ) and hydrogen peroxide (H2O2)] and reactive nitrogen species (RNS) [nitric oxide ( NO) and peroxynitrite anion (ONOO−)]. The extract presented a potent scavenging activity against all the reactive species tested, all the IC50s being found at the μg/mL level. IC50s (mean±SE) for the ROS and H2O2 were 47.6±4.6, 383±17μg/mL, respectively. The oxygen radical absorbance capacity (ORAC) value obtained for ROO was 2.17±0.22μmol Trolox equivalents/mg extract. The IC50s for NO and ONOO− were 1.95±0.29 and 1.66±0.10μg/mL, respectively. The content of total phenolics was 270±3mg of gallic acid equivalents (GAE)/g of lyophilised extract. These results showed that J. regia leaf extracts can be used as an easily accessible source of natural antioxidants. [Copyright &y& Elsevier]