Neuroprotective effect of cocoa flavonids on in vitro oxidative stress
- 499 Downloads
Cocoa is a rich source of flavonoids that, among other functions, can act as antioxidants. In living systems, the production of reactive oxygen species (ROS) activate an array of intracellular cascades, including mitogen-activated protein kinases (MAPK), that are closely associated with cell death or survival pathways.
Aim of the study
To ascertain the role of a cocoa extract and its main flavonoid, (-)-epicatechin, in an in vitro model of oxidative stress induced in a neuronal cell line.
We analyzed ROS production by fluorometry (dichlorofluorescein assay), and activation of MAPK pathways including extracellular signal-regulated kinases 1/2 (ERK 1/2), c-Jun N-terminal kinase (JNK), and p-38, by Western blot analysis.
Cells incubated with cocoa extract or (-)-epicatechin, reduced ROS production in a dose-dependent manner, reaching 35% inhibition. pJNK and p38, involved in apoptosis, were down-modulated by cocoa extract and (-)-epicatechin with p38 inhibition reaching up to 70%.
Our results show that cocoa extract and (-)-epicatechin may exert a neuroprotective action by reducing ROS production and modulating MAPK activation.
Keywordscocoa c-JNK MAPK neuronal damage oxidative stress
Analysis of variance
- ERK 1/2
Extracellular signal-regulated kinases 1/2
Glutathione-S-transferase enzyme-class Pi
c-Jun N-terminal kinase
Mitogen-activated protein kinases
Oxygen radical absorbance capacity
Reactive oxygen species
Tris buffered saline solution
TBS with 0.1% Tween 20
E.R. is the recipient of fellowships from the Generalitat de Catalunya (2003FI 00578 and 2005BE 00709).
- 1.Andrés-Lacueva C, Lamuela-Raventós RM, Jáuregui O (2000) An LC method for the analysis of cocoa phenolics. LC-GC Eur 12:902–905Google Scholar
- 4.Cho ES, Lee KW, Lee HJ (2008) Cocoa procyanidins protect PC12 cells from hydrogen-peroxide-induced apoptosis by inhibiting activation of p38 MAPK and JNK. Mutat Res 640:123–130Google Scholar
- 6.Cooper KA, Campos-Giménez E, Jiménez Alvarez D, Nagy K, Donovan JL, Williamson G (2007) Rapid reversed phase ultra-performance liquid chromatography analysis of the major cocoa polyphenols and inter-relationships of their concentrations in chocolate. J Agric Food Chem 55:2841–2847CrossRefGoogle Scholar
- 8.Crews WD Jr, Harrison DW, Wright JW (2008) A double-blind, placebo-controlled, randomized trial of the effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health: clinical findings from a sample of healthy, cognitively intact older adults. Am J Clin Nutr 87:872–880Google Scholar
- 10.Datla KP, Zbarsky V, Rai D, Parkar S, Osakabe N, Aruoma OI, Dexter DT (2007) Short-term supplementation with plant extracts rich in flavonoids protect nigrostriatal dopaminergic neurons in a rat model of Parkinson’s disease. J Am Coll Nutr 26:341–349Google Scholar
- 11.de Boer VC, Dihal AA, van der Woude H, Arts IC, Wolffram S, Alink GM, Rietjens IM, Keijer J, Hollman PC (2005) Tissue distribution of quercetin in rats and pigs. J Nutr 135:1718–1725Google Scholar
- 13.Granado-Serrano AB, Martin MA, Bravo L, Goya L, Ramos S (2006) Quercetin induces apoptosis via caspase activation, regulation of bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2). J Nutr 136:2715–2721Google Scholar
- 22.Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, Van Norren K, Van Leeuwen PAM (2001) Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 74:418–425Google Scholar
- 24.Pereda J, Sabater L, Cassinello N, Gómez-Cambronero L, Closa D, Folch-Puy E, Aparisi L, Calvete J, Cerda M, Lledo S, Vina J, Sastre J (2004) Effect of simultaneous inhibition of TNF-alpha production and xanthine oxidase in experimental acute pancreatitis: the role of mitogen activated protein kinases. Ann Surg 240:108–116CrossRefGoogle Scholar
- 31.Raza H, John A (2005) Green tea polyphenol epigallocatechin-3-gallate differentially modulates oxidative stress in PC12 cell compartments. Toxicol Appl Pharmacol 207:212–220Google Scholar
- 35.Smith MA, Hirai K, Hsiao K, Pappolla MA, Harris PL, Siedlak SL, Tabaton M, Perry G (1998) Amyloid-beta deposition in Alzheimer transgenic mice is associated with oxidative stress. J Neurochem 70:2212–2215Google Scholar
- 37.Tomas-Barberan FA, Cienfuegos-Jovellanos E, Marín A, Muguerza B, Gil-Izquierdo A, Cerda B, Zafrilla P, Morillas J, Mulero J, Ibarra A, Pasamar MA, Ramón D, Espín JC (2007) A new process to develop a cocoa powder with higher flavonoid monomer content and enhanced bioavailability in healthy humans. J Agric Food Chem 55:3926–3935CrossRefGoogle Scholar
- 39.Waetzig V, Herdegen T (2005) Context-specific inhibition of JNKs: overcoming the dilemma of protection and damage. Trends Pharmacol Sci 26:455–461Google Scholar