The
current study investigated the positive effects of blueberry
anthocyanin-rich extracts (BAE) on either peripheral or hippocampal
antioxidant defensiveness and established the connection of the improved
antioxidant status with the altered fatty acid species and gut microbiota
profile. High-fat diet-induced oxidative stress in C57BL/6 mice was
attenuated by BAE administration, which was reflected by strengthened
antioxidant enzymes, alleviated hepatic steatosis, and improved hippocampal
neuronal status. Serum lipidomics analysis indicated that the fatty
acid species were altered toward the elevated unsaturated/saturated
ratio, along with phospholipid species toward enriched n-3 polyunsaturated fatty acid compositions. The modulated antioxidant
pattern could be attributed to the increased bacteria diversity, stimulated
probiotics (Bifidobacterium and Lactobacillus) and short-chain fatty acid (SCFA) producers (Roseburia, Faecalibaculum, and Parabacteroides) improved by anthocyanins and their metabolites, which improved
the colon environment, characterized by promoted SCFAs, restored colonic
mucosa, and reorganized microbial structure. Thus, anthocyanin-rich
dietary intervention is a promising approach for the defensiveness
in human oxidative damage and neurodegeneration.
As a novel discovered regulated cell death pattern, ferroptosis has been associated with the development of Parkinson’s disease (PD) and has attracted widespread attention. Nevertheless, the relationship between ferroptosis and PD pathogenesis is still unclear. This study aims to investigate the effect of iron overload on dopaminergic (DA) neurons and its correlation with ferroptosis. Here we use nerve growth factor (NGF) induced PC12 cells which are derived from pheochromocytoma of the rat adrenal to establish a classical PD in vitro model. We found significantly decreased cell viability in NGF-PC12 cell under ammonium ferric citrate (FAC) administration. Moreover, excessive intracellular iron ions induced the increase of (reactive oxygen species) ROS release as well as the decrease of mitochondrial membrane potential in PC12-NGF cells. In addition, we also found that overloaded iron can activate cell apoptosis and ferroptosis pathways, which led to cell death. Furthermore, MPP-induced PD cells were characterized by mitochondrial shrinkage, decreased expression of glutathione peroxidase 4 (Gpx4) and ferritin heavy chain (FTH1), and increased divalent metal transporter (DMT1) and transferrin receptor 1 (TfR1) expression level. In contrast, Lip-1 and DFO increased the expression level of GPX4 and FTH1 compared to MPP-induced PD cell. In conclusion, we indicated that overloaded intracellular iron contributes to neurons death via apoptosis and ferroptosis pathways, while DFO, an iron chelator, can inhibit ferroptosis in order to protect the neurons in vitro.
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