Different behavior of polyphenols in energy metabolism of lipopolysaccharide-stimulated cells
Graphical abstract
Introduction
Oxidative stress and inflammation are the basis of the most diseases and their mechanisms are inextricably linked. An increased oxidative stress starts a cascade of pro-inflammatory cytokines that triggers inflammation (Camps et al., 2014). Dysfunctions in mitochondria, as the main organelle producing reactive oxygen species (ROS) (Handy & Loscalzo, 2012), lead to non-communicable diseases (obesity, diabetes, atherosclerosis, cancer, etc.) characterized by oxidation, inflammation and metabolic disorders (Camps & García-Heredia, 2014).
Polyphenols are secondary metabolites naturally synthetized in plants and have demonstrated several biological activities, including antioxidant and anti-inflammatory properties (Li et al., 2014). Theobroma cacao (cocoa) is worldwide consumed and common ingredient of many food products. Cocoa is a valuable source of antioxidant compounds with health benefits mainly attributed to the flavanol content (Andujar, Recio, Giner, & Rios, 2012; Cadiz-Gurrea et al., 2017) and the proanthocyanidins with high-degree of polymerization (Belscak, Komes, Horzic, Ganic, & Karlovic, 2009; Cadiz-Gurrea et al., 2014; Martin & Ramos, 2016; Schinella et al., 2010; Yasmeen, Fukagawa, & Wang, 2017). In the past decades, the bioactive constituents of cocoa have been targeted in multiple research studies confirming its health benefits and, for these reasons, the market has developed new cocoa-based products such as cocoa liquor, cocoa powder, chocolate and other derivatives and has remained stable over the last few years (Ellam & Williamson, 2013).
Lippia citriodora (lemon verbena) is a perennial plant originally from South America which was introduced into Europe at the end of the 17th century and has been widely used in infusions for its antispasmodic, antipyretic, sedative, and digestive properties. Furthermore, this plant is used in the food industry to flavor different products. Lemon verbena infusion contains significant amounts of polyphenols, including phenylpropanoid glycosides (mainly verbascoside) and flavone diglucuronides such as luteolin 7-diglucuronide, with high anti-inflammatory and antioxidant properties (Funes et al., 2009; Quirantes-Piné, Funes, Micol, Segura-Carretero, & Fernández-Gutiérrez, 2009). In the last decade, the potential of L. citriodora extract supplementation as a nutraceutical is under consideration with the aim to find phytotherapies, which contribute to ameliorate diseases with less adverse effects than synthetic drugs (Cádiz-Gurrea et al., 2017).
In this work, antioxidant and anti-inflammatory properties of food polyphenols found in cocoa and lemon verbena were tested on two mouse embryonic fibroblast (MEF) cell lines: 1) knock-out mice for paraoxonaxe-1, an antioxidant endogenous enzyme, as model of oxidation (PON-1 KO cells) and 2) transgenic mice overexpressing the monocyte chemoattractant protein 1 (MCP-1), a proinflammatory cytokine, as model of inflammation (tgMCP-1 cells). To analyze the impact of polyphenols in the energy management in these conditions, a targeted metabolomics approach was performed on gas chromatography coupled to a quadrupole time-of-flight mass spectrometer and an electron impact source.
Section snippets
Chemicals
Methanol, dimethylsulphoxide (DMSO), methoxyamine hydrochloride, pyridine and lipopolysaccharide (LPS) were purchased from Sigma-Aldrich (St. Louis, MO, USA). N-methyl-N-trimethylsilyl-trifluoroacetamide with 1% trimethylchlorosilane (TMS) and RIPA lysis and extraction buffer were purchased from Thermo Fisher Scientific (Waltham, MA, USA). Ultrapure type-1 water was obtained from a Milli Q water system (Merck Millipore, Darmstadt, Germany). DMEM medium, fetal bovine serum (FBS),
Results and discussion
Understanding oxidation and inflammation as the two fronts of a same coin is crucial to assess the mechanisms involved in appearance, progression and resolution (or chronicity) of these pathophysiological conditions and how they are interconnected to metabolism (Griffiths, Gao, & Pararasa, 2017). Inflammation and oxidation are related to several “metabolic diseases”, including obesity, atherosclerosis and cancer (Camps, García-Heredia, Hernández-Aguilera, & Joven, 2016), and mitochondrial
Conclusions
In the present study, we highlight the different behavior of polyphenols as antioxidant and anti-inflammatory molecules. T. cacao extract is responsible to partially return the impairment in the energy management during a pro-oxidant status in PON-1 KO cells probably through the antioxidant properties of theobromine, flavan-3-ol monomers and procyanidins. On the contrary, L. citriodora extract possess a partial effect on the energy metabolism in a pro-inflammatory scenario probably due to the
Acknowledgements
This work was supported by the project AGL2015-6795-C3-1-R and AGL2015-67995-C3-2-R (Spanish Ministry of Science and Innovation), as well as P11-CTS-7625 (Andalusian Regional Government Council of Innovation and Science), PROMETEO/2016/006 and ACIF/2016/230 (Generalitat Valenciana), CIBERobn CB12/03/30038 Fisiopatología de la Obesidad y la Nutrición (Instituto de Salud Carlos III), PI15/00285 (Plan Nacional de I+D+I, Spain, Instituto de Salud Carlos III, co-founded by the European Regional
Conflict of interest
Authors declare no conflicts of interest.
Author contributions
MLCG performed the experiments in cells and analyzed data. VM provides plant extracts and help in the experimental design. JJ and ASC helped to write the manuscript and providing the laboratory facilities. SFA supervised the experiments, the data analysis and wrote the manuscript.
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