Corylus avellana cultivar “Tonda di Giffoni”, source of antioxidant diarylheptanoids: Biological evaluation and molecular docking analysis

Hazelnut “Tonda di Giffoni” (Corylus avellana L.) is a PGI (Protected Geographical Indication) product of the Campania region, Southern Italy, marked for its processing quality which guarantees origin, typical features, high physicochemical quality, and organoleptic properties. Previous investigations on hazelnut and its byproducts revealed the presence of diarylheptanoid derivatives, natural compounds with antioxidant properties. With the aim of exploring the nutraceutical properties of hazelnut diarylheptanoids, the antioxidant properties of giffonins E (1), H (2), and J (3), three cyclic diaryletherheptanoids, and carpinontriol B (4), a cyclic diarylheptanoid, were investigated. Tested compounds showed significant protection against hydrogen peroxide (H2O2)-induced cytotoxic damage in human neuroblastoma and embryonic kidney cell lines. Compounds 1–4 were also able to prevent oxidative stress by decreasing reactive oxygen species (ROS) production and levels of lipid peroxidation, and attenuating cell apoptosis (caspase-3 activity). Moreover, considering that the nuclear factor erythroid 2-related factor 2 (Nrf2) is responsible for regulating an extensive panel of antioxidant enzymes, the capability of these natural products to disrupt the interaction between Kelch-like ECH-associated protein 1 (Keap1), thereby activating the Nrf2-mediated pathway, was evaluated by molecular docking experiments and in vitro tests. The Western blot analysis revealed that giffonin H and carpinontriol B had an indirect antioxidant action, as evidenced by a significant rise in the translocated protein following their administration.