Abstract
Caffeoylquinic acid (CQA) derivatives are polyphenolic compounds found in wide variety of plants. Previously, we have demonstrated that di-CQA and tri-CQA may be neuroprotective through their ability to promote intracellular adenosine-5′-triphosphate (ATP) generation and by up-regulation of glycolytic enzyme expression. In the present study we have investigated the effect of di-CQA and tri-CQA on energy metabolism in SH-SY5Y cells using a metabolomic approach. Results indicate that di-CQA treatment of SH-SY5Y cells significantly increases the production of an array of glycolysis metabolites and tricarboxylic acid (TCA) cycle metabolites, including acetyl-CoA, succinic acid, fumaric acid, and malic acid. Tri-CQA treatment was also observed to increase the levels of all glycolysis and TCA cycle metabolites and evoked a stronger effect than that of di-CQA. In addition to their effects on glycolytic metabolites, di-CQA and tri-CQA exposure also induced a significant increase in the production of ATP, ADP, GTP, and GDP. Our results suggest that CQA-induction of intracellular ATP synthesis is mediated by the activation of central metabolic pathways including the activation of glycolysis and the TCA cycle.