Annurca Apple-Derived Polyphenols, Bioactive Fractions and By-Products as Context-Dependent Redox Modulators: Molecular Mechanisms and Nutraceutical Perspectives—A Narrative Review

Annurca apple (Malus domestica cv. Annurca) is a traditional Southern Italian cultivar increasingly recognized as a polyphenol-rich food matrix with functional and nutraceutical relevance. Its distinctive post-harvest reddening process, together with tissue-specific differences among flesh, peel and core, influences its phytochemical profile, antioxidant capacity and biological activity. In addition, Annurca apple by-products, including peel and core fractions, are emerging as sustainable sources of food-derived bioactives. This review critically summarizes current evidence on Annurca apple-derived polyphenols, bioactive fractions and by-products, focusing on their molecular mechanisms, context-dependent redox behavior and translational potential. Available studies indicate that Annurca-derived compounds and matrices should not be interpreted merely as antioxidant sources but rather as modulators of redox-sensitive cellular pathways whose effects depend on fruit fraction, ripening stage, extract composition, dose, biological model and cellular context. In normal cellular models, Annurca-derived extracts and fractions have shown cytoprotective effects against oxidative damage, mercury-induced erythrocyte alterations, phosphatidylserine externalization, advanced glycation end product (AGE)-induced cytotoxicity and oxidative stress-induced senescence. These effects involve mechanisms related to ROS modulation, erythrocyte membrane homeostasis, calcium-dependent PLSCR1 regulation, antiglycative activity, endothelial protection and senescence-associated pathways. Conversely, in cancer cell models, Annurca polyphenols may exert pro-oxidant and pro-apoptotic effects, mainly involving ROS/JNK signaling, inhibition of cell survival, modulation of epithelial–mesenchymal plasticity and reduced migration. Additional evidence on lipid metabolism, skin and hair biology, neuroprotective targets and by-product valorization supports broader functional and nutraceutical applications. However, most evidence remains preclinical and often relies on concentrated extracts or specific formulations. Future studies should address extract standardization, phytochemical fingerprinting, bioaccessibility, gut microbiota metabolism, circulating metabolites, dose relevance and clinical validation to clarify whether Annurca-derived bioactives can be developed as evidence-based functional ingredients or nutraceutical candidates.