Different behavior of polyphenols in energy metabolism of lipopolysaccharide-stimulated cells.

Energy metabolism is one of the main sources of reactive oxygen species leading to oxidation and inflammation in pathophysiological processes. Lipopolysaccharide (LPS)-activated mouse embryonic fibroblast (MEF) cell lines from knock-out mice for paraoxonase-1 and from transgenic mice overexpressing monocyte chemoattractant protein-1 were obtained as model of pro-oxidant and pro-inflammatory scenarios. Theobroma cacao and Lippia citriodora (worldwide consumed and common ingredient of many food products) were tested in these cell models to assess the action of polyphenols in the energy management. Our metabolomics experiments show a different behavior of polyphenols: T. cacao extract partially reverts the effect of LPS in a pro-oxidant scenario through the antioxidant properties of theobromine, flavonols and procyanidins, while L. citriodora seems to act mainly in a pro-inflammatory cell model through the action of verbascoside decreasing the production of pro-inflammatory cytokines and MCP-1. Nevertheless, the action of polyphenols cannot be attributed only to a mechanism of action but the sum of different modulations in biological pathways. The capacity of both plant extracts to decrease α-ketoglutarate levels merits special attention due to the implications in future medicine. The action of polyphenols modulating oxidative stress, cytokine production and epigenetic changes make an interesting source of bioactive compounds for nutraceutical or functional food purposes.