Hazelnut and Defatted Hazelnut Pulp Extracts as Natural Iron Chelators: Iron-Chelating, Antioxidant, and Anti-Inflammatory Properties in Iron Overload

Iron overload induces oxidative stress, lipid peroxidation, and inflammatory responses, collectively contributing to cellular and tissue injury. Although synthetic iron chelators are widely used in clinical practice, their associated adverse effects and treatment-related costs highlight the need to investigate naturally derived compounds as potential alternative therapeutic agents. This study comprehensively evaluated the iron-chelating, antioxidant, and anti-inflammatory properties of hazelnut samples encompassing Giresun-quality (Beşikdüzü, Vakfıkebir, and Çarşıbaşı), Levant-quality (Araklı, Arsin, and Yomra), and Pikola-type varieties, alongside extracts derived from defatted hazelnut pulp. Following qualitative and quantitative phytochemical characterization, antioxidant capacity was assessed using DPPH, CUPRAC, FRAP, and TOAC assays, while iron-binding capacity was evaluated under simulated gastric (pH 2) and intestinal (pH 6) conditions using atomic absorption spectroscopy and the ferrozine assay. To investigate hepatic protection, the iron-chelating potential of the extracts was examined in Hep3B cells exposed to iron overload. Extract C (80% ethanolic extract of ground hazelnuts) exhibited the most pronounced iron-chelating activity, achieving iron-binding efficiencies of 77–88% under simulated gastrointestinal conditions and 90% in the ferrozine assay, while decreasing intracellular iron accumulation in Hep3B cells by approximately 83–84%. Furthermore, Extract C effectively mitigated iron-induced oxidative stress, as evidenced by reduced malondialdehyde (MDA) levels and the restoration of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, the extracts additionally suppressed nitrite accumulation and decreased prostaglandin E2 (PGE2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. Our findings highlight the potential of hazelnut-based extracts as therapeutic candidates for the management of iron overload owing to their iron-chelating, antioxidant, and anti-inflammatory properties.