Polyphenolic extract attenuates fatty acid-induced steatosis and oxidative stress in hepatic and endothelial cells
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Phenolic compounds (PC) of virgin olive oil exert several biochemical and pharmacological beneficial effects. Some dietary PC seem to prevent/improve obesity and metabolic-related disorders such as non-alcoholic fatty liver disease (NAFLD). We investigated the possible effects of PC extracted from olive pomace (PEOP) and of the main single molecules present in the extract (tyrosol, apigenin, oleuropein, p-coumaric and caffeic acid) in protecting hepatocytes and endothelial cells against triglyceride accumulation and oxidative stress.
Rat hepatoma and human endothelial cells were exposed to a mixture of oleate/palmitate to mimic the condition of NAFLD and atherosclerosis, respectively. Then, cells were incubated for 24 h in the absence or in the presence of PC or PEOP. Different parameters were evaluated, such as lipid accumulation and oxidative stress-related markers.
In hepatic cells, expression of peroxisome proliferator-activated receptors (PPARs) and of stearoyl-CoA desaturase 1 (SCD-1) were assessed as index of lipid metabolism. In endothelial cells, expression of intercellular adhesion molecule-1 (ICAM-1), activation of nuclear factor kappa-B (NF-kB), release of nitric oxide (NO), and wound-healing rate were assessed as index of inflammation.
PEOP extract ameliorated hepatic lipid accumulation and lipid-dependent oxidative imbalance thus showing potential applications as therapeutic agent tuning down hepatosteatosis and atherosclerosis.
KeywordsNon-alcoholic fatty liver disease Atherosclerosis Olive pomace Phenolic compound Oxidative stress
This research was supported by grants from MIUR-COFIN (Prot. 20089SRS2X_002), Compagnia San Paolo Torino (Prat. No. 2009.1824-1067/IT/pv), University of Genova (no. 2015), European Joint Programming Initiative “A Healthy Diet for a Healthy Life (JPI HDHL)–National Project Wellness, Nutrition, Sport and Exercise prevention (WISE) 2013–16 (PP).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 9.Rigacci S, Stefani M. Nutraceutical Properties of Olive Oil Polyphenols. An Itinerary from Cultured Cells through Animal Models to Humans. Int J Mol Sci 2016;17. doi: 10.3390/ijms17060843
- 10.Mata P, Alvarez-Sala LA, Rubio MJ, Nuno J, De Oya M (1992) Effects of long-term monounsaturated- vs polyunsaturated-enriched diets on lipoproteins in healthy men and women. Am J Clin Nutr 55:846–850Google Scholar
- 13.Reaven P, Parthasarathy S, Grasse BJ, Miller E, Steinberg D, Witztum JL (1993) Effects of oleate-rich and linoleate-rich diets on the susceptibility of low density lipoprotein to oxidative modification in mildly hypercholesterolemic subjects. J Clin Invest 91:668–676. doi: 10.1172/JCI116247 CrossRefGoogle Scholar
- 17.Zern TL, Fernandez ML (2005) cardioprotective effects of dietary polyphenols. J Nutr 2291–4Google Scholar
- 23.Yu S, Matsusue K, Kashireddy P, Cao W-Q, Yeldandi V, Yeldandi AV et al (2003) Adipocyte-specific gene expression and adipogenic steatosis in the mouse liver due to peroxisome proliferator-activated receptor gamma1 (PPARgamma1) overexpression. J Biol Chem 278:498–505. doi: 10.1074/jbc.M210062200 CrossRefGoogle Scholar
- 27.Gay AN, Mushin OP, Lazar DA, Naik-Mathuria BJ, Yu L, Gobin A, Smith CW OO (2011) Wound healing characteristics of ICAM-1 null mice devoid of all isoforms of ICAM-1. J Surg Res 1–7. doi: 10.1016/j.jss.2011.06.053
- 34.Hoek-van den Hil EF, van Schothorst EM, van der Stelt I, Swarts HJM, van Vliet M, Amolo T, et al (2015) Direct comparison of metabolic health effects of the flavonoids quercetin, hesperetin, epicatechin, apigenin and anthocyanins in high-fat-diet-fed mice. Genes Nutr 10:469. doi: 10.1007/s12263-015-0469-z
- 35.Ragab SMM, Abd Elghaffar SK, El-Metwally TH, Badr G, Mahmoud MH, Omar HM (2015) Effect of a high fat, high sucrose diet on the promotion of non-alcoholic fatty liver disease in male rats: the ameliorative role of three natural compounds. Lipids Health Dis 14:83. doi: 10.1186/s12944-015-0087-1 CrossRefGoogle Scholar
- 39.Zhou H, Liu X, Liu L, Yang Z, Zhang S, Tang M, et al. Oxidative stress and apoptosis of human brain microvascular endothelial cells induced by free fatty acids. J Int Med Res 37:1897–903Google Scholar
- 43.Vergani L, Vecchione G, Baldini F, Voci A, Ferrari PF, Aliakbarian B, Casazza AAPP (2016) Antioxidant and hepatoprotective potentials of phenolic compounds from olive pomace. Chem Eng Trans 49:475–480Google Scholar
- 48.Iguchi H, Kojo S, Ikeda M. Lipid peroxidation and disintegration of the cell membrane structure in cultures of rat lung fibroblasts treated with asbestos. J Appl Toxicol 13:269–75Google Scholar
- 49.Grasselli E, Voci A, Pesce C, Canesi L, Fugassa E, Gallo G et al (2010) PAT protein mRNA expression in primary rat hepatocytes: effects of exposure to fatty acids. Int J Mol Med 25:505–512Google Scholar
- 54.Sun C, Wu Z, Wang Z, Zhang H (2015) Effect of ethanol/water solvents on phenolic profiles and antioxidant properties of Beijing propolis extracts. Evidence-Based Complementary and Alternative Medicine 595393, 9Google Scholar
- 56.Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong C-P, Nettleton JA et al (2007) Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr 85:895–909Google Scholar
- 61.Byrne CD. Fatty liver: role of inflammation and fatty acid nutrition. Prostaglandins Leukot Essent Fatty Acids 82:265–71. doi: 10.1016/j.plefa.2010.02.012
- 63.Roebuck KA, Finnegan A (1999) Regulation of intercellular adhesion molecule-1 (CD54) gene expression. J Leukoc Biol 66:876–888Google Scholar
- 64.Kuhlencordt PJ, Rosel E, Gerszten RE, Morales-Ruiz M, Dombkowski D, Atkinson WJ et al (2004) Role of endothelial nitric oxide synthase in endothelial activation: insights from eNOS knockout endothelial cells. Am J Physiol Cell Physiol 286:C1195–C1202. doi: 10.1152/ajpcell.00546.2002 CrossRefGoogle Scholar