Epigenetic-based antioxidant effect of an ethanolic extract of Corylus avellana L . on THLE-2 human primary hepatocytes.

The ethanolic extract of Corylus avellana L hazelnut, prepared in our laboratories, has been previously characterized by liquid chromatography coupled to high resolution mass spectrometry. We here aimed at testing the antioxidant effect of such extract in H 2 O 2 -challenged THLE-2 human primary hepatocytes and verified whether it might be based on microRNA-34b/c expression changes. We here demonstrate that miR-34b/miR-34c undergo significant stimulation (≥2-fold change, p  < 0.05) in THLE-2 when treated for 72h with not-toxic hazelnut concentrations (0.04-0.4 mg/ml), when compared with 0.06% ethanol control. When administered with H 2 O 2 (1000-2000 µM, 24h), THLE-2 are significantly protected from oxidative stress if pre-treated with hazelnut, the H 2 O 2 -driven cytotoxicity and reactive oxygen species generation being recovered by hazelnut extract, through miR-34b/c stimulation. Although preliminary, our findings pave the way for further preclinical studies aimed at validating the possible health-related application of hazelnut matrix, and/or its metabolites, as powerful epigenetic-based drugs, food supplements or nutraceuticals.