Abstract

Oxidative stress response is closely related to neurodegenerative diseases. This study aimed to investigate the cytoprotective effects of luteolin on glutamate-induced oxidative stress injury in PC12 cells. GC-MS combined with multivariate statistical approaches was used to perform metabolomics studies to assess the possible mechanisms. Our results identified 23 metabolites as differential expressed metabolites in the glutamate group, including cysteine content in cells that decreased drastically. This suggests that glutathione synthesis, which balances the redox state of cells, was affected. Luteolin inhibits the reduction in viability in glutamate-induced PC12 cells and regulates 13 differential expressed metabolites in glutamate-induced cell damage. These metabolites associated with luteolin included glycine, serine, and threonine metabolism; glyoxylate and dicarboxylate metabolism; aminoacyl-tRNA biosynthesis; cysteine and methionine metabolism; inositol phosphate metabolism; and starch and sucrose metabolism. In summary, the systemic antioxidant capacity of luteolin in PC12 cells is related to its regulation of amino acid, glucose, and nucleotide metabolism pathways.

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