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

The ethanolic extract of 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 HO-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,  < 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 HO (1000-2000 µM, 24h), THLE-2 are significantly protected from oxidative stress if pre-treated with hazelnut, the HO-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.