The agri-food industrial by-products olive leaves and myrtle pomace exhibit strong protective power against oxidative cellular damage. An in vitro NMR study

Neurodegenerative diseases are associated with oxidative cellular stress. This study investigates the neuroprotective effects of polyphenol-rich extracts from the agri-food industrial by-products myrtle pomace and olive leaves. This in vitro study employs PC12 cells exposed to 6-hydroxydopamine (6-OHDA) as a model of oxidative neurotoxicity. H NMR metabolomics was applied to analyze the cellular exo- and endometabolome. Exposure to 6-OHDA caused profound metabolic disturbances, including reduced glucose uptake, altered TCA cycle intermediates, and a significant increase in AMP, acetate, taurine, and branched-chain amino acids (BCAAs) (p < 0.001), consistent with mitochondrial dysfunction and redox imbalance. Moreover, lipidomic profiling revealed enhanced lipid peroxidation, membrane fragmentation, and cholesterol depletion. Pre-treatment with ME or OLE (10 and 100 μg/mL) effectively restored normal metabolic profiles, normalized AMP, taurine, and BCAA levels (p < 0.001), and counteracted lipid peroxidation and phospholipid degradation, indicating improved mitochondrial function and membrane preservation. Both extracts elicited comparable metabolic responses, suggesting a shared antioxidant mechanism linked to their polyphenolic composition. Overall, this study provides comprehensive metabolomic evidence that myrtle and olive by-products mitigate oxidative neurotoxicity through energy and redox homeostasis restoration. These findings highlight the theoretical significance of targeting metabolic resilience in oxidative stress models and the practical potential of upcycling agri-food residues into sustainable neuroprotective nutraceuticals.