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Published in: European Journal of Nutrition 5/2015

01-08-2015 | Original Contribution

Sicilian pistachio (Pistacia vera L.) nut inhibits expression and release of inflammatory mediators and reverts the increase of paracellular permeability in IL-1β-exposed human intestinal epithelial cells

Authors: C. Gentile, A. Perrone, A. Attanzio, L. Tesoriere, M. A. Livrea

Published in: European Journal of Nutrition | Issue 5/2015

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Abstract

Background

Dietary approaches to control inflammatory bowel diseases (IBD) may include proanthocyanidin-rich foods. Our previous research showed that a hydrophilic extract from Sicilian pistachio nut (HPE) contains substantial amounts of proanthocyanidins and possesses anti-inflammatory activities.

Purpose

We studied the effects of HPE and of its polymeric proanthocyanidin fraction (PPF) in a cell model that simulated some conditions of IBD, consisting of interleukin (IL)-1β-stimulated Caco-2 cells.

Methods

HPE was prepared by Pistacia vera L. nuts, and PPF was isolated from HPE by adsorbance chromatography. Proanthocyanidins were quantified as anthocyanidins after acidic hydrolysis. Differentiated Caco-2 cells were pre-incubated with HPE or PPF and then were exposed to IL-1β. Cell viability and parameters associated with nuclear factor-κB (NF-κB) activation were assayed. Adsorption of polymeric proanthocyanidins to the cell membrane was investigated by transepithelial electrical resistance (TEER) measurements.

Results

HPE decreased prostaglandin (PG)E2 production, IL-6 and IL-8 release, and cyclooxygenase (COX)-2 expression. HPE also inhibited the increase in paracellular permeability and reduced NF-κB activation. Polymeric proanthocyanidins, tested at a concentration comparable with their content in HPE, produced effects comparable to HPE. Finally, cell exposure to PPF increases TEER of the epithelial monolayers.

Conclusion

Our results provide evidence that pistachio nut components inhibit inflammatory response of intestinal epithelial cells in vitro and indicate polymeric proanthocyanidins as the major bioactive nut components. The protection implies inhibition of NF-κB activation and occurs in parallel with the adsorption of polymeric proanthocyanidins to cell membrane. Our findings suggest that intake of small amounts of pistachio nut can exert beneficial effects to gastrointestinal pathophysiology.
Literature
2.
go back to reference Sartor RB (1997) Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases. Am J Gastroenterol 92(12 Suppl):5S–11S Sartor RB (1997) Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases. Am J Gastroenterol 92(12 Suppl):5S–11S
3.
go back to reference Netsch MI, Gutmann H, Aydogan C, Drewe J (2006) Green tea extract induces interleukin-8 (IL-8) mRNA and protein expression but specifically inhibits IL-8 secretion in caco-2 cells. Planta Med 72(8):697–702. doi:10.1055/s-2006-931597 CrossRef Netsch MI, Gutmann H, Aydogan C, Drewe J (2006) Green tea extract induces interleukin-8 (IL-8) mRNA and protein expression but specifically inhibits IL-8 secretion in caco-2 cells. Planta Med 72(8):697–702. doi:10.​1055/​s-2006-931597 CrossRef
5.
go back to reference Mitjavila MT, Moreno JJ (2012) The effects of polyphenols on oxidative stress and the arachidonic acid cascade. Implications for the prevention/treatment of high prevalence diseases. Biochem Pharmacol 84(9):1113–1122. doi:10.1016/j.bcp.2012.07.017 CrossRef Mitjavila MT, Moreno JJ (2012) The effects of polyphenols on oxidative stress and the arachidonic acid cascade. Implications for the prevention/treatment of high prevalence diseases. Biochem Pharmacol 84(9):1113–1122. doi:10.​1016/​j.​bcp.​2012.​07.​017 CrossRef
6.
go back to reference Rasmussen SE, Frederiksen H, Struntze Krogholm K, Poulsen L (2005) Dietary proanthocyanidins: occurrence, dietary intake, bioavailability, and protection against cardiovascular disease. Mol Nutr Food Res 49(2):159–174. doi:10.1002/mnfr.200400082 CrossRef Rasmussen SE, Frederiksen H, Struntze Krogholm K, Poulsen L (2005) Dietary proanthocyanidins: occurrence, dietary intake, bioavailability, and protection against cardiovascular disease. Mol Nutr Food Res 49(2):159–174. doi:10.​1002/​mnfr.​200400082 CrossRef
7.
8.
go back to reference Rios LY, Bennett RN, Lazarus SA, Rémésy C, Scalbert A, Williamson G (2002) Cocoa procyanidins are stable during gastric transit in humans. Am J Clin Nutr 76(5):1106–1110 Rios LY, Bennett RN, Lazarus SA, Rémésy C, Scalbert A, Williamson G (2002) Cocoa procyanidins are stable during gastric transit in humans. Am J Clin Nutr 76(5):1106–1110
9.
go back to reference Deprez S, Mila I, Huneau JF, Tome D, Scalbert A (2001) Transport of proanthocyanidin dimer, trimer, and polymer across monolayers of human intestinal epithelial Caco-2 cells. Antioxid Redox Signal 3(6):957–967. doi:10.1089/152308601317203503 CrossRef Deprez S, Mila I, Huneau JF, Tome D, Scalbert A (2001) Transport of proanthocyanidin dimer, trimer, and polymer across monolayers of human intestinal epithelial Caco-2 cells. Antioxid Redox Signal 3(6):957–967. doi:10.​1089/​1523086013172035​03 CrossRef
10.
go back to reference Yoshioka Y, Akiyama H, Nakano M, Shoji T, Kanda T, Ohtake Y, Takita T, Matsuda R, Maitani T (2008) Orally administered apple procyanidins protect against experimental inflammatory bowel disease in mice. Int Immunopharmacol 8(13–14):1802–1807. doi:10.1016/j.intimp.2008.08.021 CrossRef Yoshioka Y, Akiyama H, Nakano M, Shoji T, Kanda T, Ohtake Y, Takita T, Matsuda R, Maitani T (2008) Orally administered apple procyanidins protect against experimental inflammatory bowel disease in mice. Int Immunopharmacol 8(13–14):1802–1807. doi:10.​1016/​j.​intimp.​2008.​08.​021 CrossRef
11.
go back to reference Li XL, Cai YQ, Qin H, Wu YJ (2008) Therapeutic effect and mechanism of proanthocyanidins from grape seeds in rats with TNBS-induced ulcerative colitis. Can J Physiol Pharmacol 86(12):841–849. doi:10.1139/Y08-089 CrossRef Li XL, Cai YQ, Qin H, Wu YJ (2008) Therapeutic effect and mechanism of proanthocyanidins from grape seeds in rats with TNBS-induced ulcerative colitis. Can J Physiol Pharmacol 86(12):841–849. doi:10.​1139/​Y08-089 CrossRef
12.
go back to reference Wang YH, Yang XL, Wang L, Cui MX, Cai YQ, Li XL, Wu YJ (2010) Effects of proanthocyanidins from grape seed on treatment of recurrent ulcerative colitis in rats. Can J Physiol Pharmacol 88(9):888–898. doi:10.1139/y10-071 CrossRef Wang YH, Yang XL, Wang L, Cui MX, Cai YQ, Li XL, Wu YJ (2010) Effects of proanthocyanidins from grape seed on treatment of recurrent ulcerative colitis in rats. Can J Physiol Pharmacol 88(9):888–898. doi:10.​1139/​y10-071 CrossRef
14.
go back to reference Velmurugan B, Singh RP, Kaul N, Agarwal R, Agarwal C (2010) Dietary feeding of grape seed extract prevents intestinal tumorigenesis in APCmin/+ mice. Neoplasia 12(1):95–102. doi:10.1593/neo.91718 CrossRef Velmurugan B, Singh RP, Kaul N, Agarwal R, Agarwal C (2010) Dietary feeding of grape seed extract prevents intestinal tumorigenesis in APCmin/+ mice. Neoplasia 12(1):95–102. doi:10.​1593/​neo.​91718 CrossRef
18.
go back to reference Sari I, Baltaci Y, Bagci C, Davutoglu V, Erel O, Celik H, Ozer O, Aksoy N, Aksoy M (2010) Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative status: a prospective study. Nutrition 26(4):399–404. doi:10.1016/j.nut.2009.05.023 CrossRef Sari I, Baltaci Y, Bagci C, Davutoglu V, Erel O, Celik H, Ozer O, Aksoy N, Aksoy M (2010) Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative status: a prospective study. Nutrition 26(4):399–404. doi:10.​1016/​j.​nut.​2009.​05.​023 CrossRef
19.
go back to reference Gentile C, Tesoriere L, Butera D, Fazzari M, Monastero M, Allegra M, Livrea MA (2007) Antioxidant activity of Sicilian pistachio (Pistacia vera L. var. Bronte) nut extract and its bioactive components. J Agric Food Chem 55(3):643–648. doi:10.1021/jf062533i CrossRef Gentile C, Tesoriere L, Butera D, Fazzari M, Monastero M, Allegra M, Livrea MA (2007) Antioxidant activity of Sicilian pistachio (Pistacia vera L. var. Bronte) nut extract and its bioactive components. J Agric Food Chem 55(3):643–648. doi:10.​1021/​jf062533i CrossRef
20.
go back to reference Gentile C, Allegra M, Angileri F, Pintaudi AM, Livrea MA, Tesoriere L (2012) Polymeric proanthocyanidins from Sicilian pistachio (Pistacia vera L.) nut extract inhibit lipopolysaccharide-induced inflammatory response in RAW 264.7 cells. Eur J Nutr 51(3):353–363. doi:10.1007/s00394-011-0220-5 CrossRef Gentile C, Allegra M, Angileri F, Pintaudi AM, Livrea MA, Tesoriere L (2012) Polymeric proanthocyanidins from Sicilian pistachio (Pistacia vera L.) nut extract inhibit lipopolysaccharide-induced inflammatory response in RAW 264.7 cells. Eur J Nutr 51(3):353–363. doi:10.​1007/​s00394-011-0220-5 CrossRef
21.
go back to reference Jordão AM, Gonçalves FJ, Correia AC, Cantão J, Rivero-Pérez MD, González Sanjosé ML (2010) Proanthocyanidin content, antioxidant capacity and scavenger activity of Portuguese sparkling wines (Bairrada Appellation of Origin). J Sci Food Agric 90:2144–2152. doi:10.1002/jsfa.4064 Jordão AM, Gonçalves FJ, Correia AC, Cantão J, Rivero-Pérez MD, González Sanjosé ML (2010) Proanthocyanidin content, antioxidant capacity and scavenger activity of Portuguese sparkling wines (Bairrada Appellation of Origin). J Sci Food Agric 90:2144–2152. doi:10.​1002/​jsfa.​4064
23.
go back to reference Tesoriere L, Attanzio A, Allegra M, Gentile C, Livrea MA (2014) Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. Br J Nutr 111(3):415–423. doi:10.1017/S0007114513002663 CrossRef Tesoriere L, Attanzio A, Allegra M, Gentile C, Livrea MA (2014) Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. Br J Nutr 111(3):415–423. doi:10.​1017/​S000711451300266​3 CrossRef
24.
go back to reference Banan A, Choudhary S, Zhang Y, Fields JZ, Keshavarzian A (2000) Oxidant-induced intestinal barrier disruption and its prevention by growth factors in a human colonic cell line: role of the microtubule cytoskeleton. Free Radic Biol Med 28(5):727–738. doi:10.1016/S0891-5849(00)00160-X CrossRef Banan A, Choudhary S, Zhang Y, Fields JZ, Keshavarzian A (2000) Oxidant-induced intestinal barrier disruption and its prevention by growth factors in a human colonic cell line: role of the microtubule cytoskeleton. Free Radic Biol Med 28(5):727–738. doi:10.​1016/​S0891-5849(00)00160-X CrossRef
25.
go back to reference Tesoriere L, Gentile C, Angileri F, Attanzio A, Tutone M, Allegra M, Livrea MA (2013) Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix. Eur J Nutr 52(3):1077–1087. doi:10.1007/s00394-012-0414-5 CrossRef Tesoriere L, Gentile C, Angileri F, Attanzio A, Tutone M, Allegra M, Livrea MA (2013) Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix. Eur J Nutr 52(3):1077–1087. doi:10.​1007/​s00394-012-0414-5 CrossRef
26.
go back to reference Artursson P (1990) Epithelial transport of drugs in cell culture. I: a model for studying the passive diffusion of drugs over intestinal (Caco-2) absorptive cells. J Pharm Sci 79:476–482. doi:10.1002/jps.2600790604 CrossRef Artursson P (1990) Epithelial transport of drugs in cell culture. I: a model for studying the passive diffusion of drugs over intestinal (Caco-2) absorptive cells. J Pharm Sci 79:476–482. doi:10.​1002/​jps.​2600790604 CrossRef
29.
go back to reference Al-Sadi RM, Ma TY (2007) IL-1beta causes an increase in intestinal epithelial tight junction permeability. J Immunol 178(7):4641–4649CrossRef Al-Sadi RM, Ma TY (2007) IL-1beta causes an increase in intestinal epithelial tight junction permeability. J Immunol 178(7):4641–4649CrossRef
32.
go back to reference Daig R, Andus T, Aschenbrenner E, Falk W, Scholmerich J, Gross V (1996) Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease. Gut 38:216–222. doi:10.1136/gut.38.2.216 CrossRef Daig R, Andus T, Aschenbrenner E, Falk W, Scholmerich J, Gross V (1996) Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease. Gut 38:216–222. doi:10.​1136/​gut.​38.​2.​216 CrossRef
33.
go back to reference Romier-Crouzet B, Van De Walle J, During A, Joly A, Rousseau C, Henry O, Larondelle Y, Schneider YJ (2009) Inhibition of inflammatory mediators by polyphenolic plant extracts in human intestinal Caco-2 cells. Food Chem Toxicol 47(6):1221–1230. doi:10.1016/j.fct.2009.02.015 CrossRef Romier-Crouzet B, Van De Walle J, During A, Joly A, Rousseau C, Henry O, Larondelle Y, Schneider YJ (2009) Inhibition of inflammatory mediators by polyphenolic plant extracts in human intestinal Caco-2 cells. Food Chem Toxicol 47(6):1221–1230. doi:10.​1016/​j.​fct.​2009.​02.​015 CrossRef
36.
go back to reference Van De Walle J, Hendrickx A, Romier B, Larondelle Y, Schneider YJ (2010) Inflammatory parameters in Caco-2 cells: effect of stimuli nature, concentration, combination and cell differentiation. Toxicol In Vitro 24(5):1441–1449. doi:10.1016/j.tiv.2010.04.002 CrossRef Van De Walle J, Hendrickx A, Romier B, Larondelle Y, Schneider YJ (2010) Inflammatory parameters in Caco-2 cells: effect of stimuli nature, concentration, combination and cell differentiation. Toxicol In Vitro 24(5):1441–1449. doi:10.​1016/​j.​tiv.​2010.​04.​002 CrossRef
37.
go back to reference Erlejman AG, Jaggers G, Fraga CG, Oteiza PI (2008) TNFalpha-induced NF-kappaB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells. Arch Biochem Biophys 476(2):186–195. doi:10.1016/j.abb.2008.01.024 CrossRef Erlejman AG, Jaggers G, Fraga CG, Oteiza PI (2008) TNFalpha-induced NF-kappaB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells. Arch Biochem Biophys 476(2):186–195. doi:10.​1016/​j.​abb.​2008.​01.​024 CrossRef
38.
go back to reference Bruewer M, Luegering A, Kucharzik T, Parkos CA, Madara JL, Hopkins AM, Nusrat A (2003) Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms. J Immunol 171(11):6164–6172CrossRef Bruewer M, Luegering A, Kucharzik T, Parkos CA, Madara JL, Hopkins AM, Nusrat A (2003) Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms. J Immunol 171(11):6164–6172CrossRef
41.
go back to reference Verstraeten SV, Keen CL, Schmitz HH, Fraga CG, Oteiza PI (2003) Flavan-3-ols and procyanidins protect liposomes against lipid oxidation and disruption of the bilayer structure. Free Radic Biol Med 34(1):84–92. doi:10.1016/S0891-5849(02)01185-1 CrossRef Verstraeten SV, Keen CL, Schmitz HH, Fraga CG, Oteiza PI (2003) Flavan-3-ols and procyanidins protect liposomes against lipid oxidation and disruption of the bilayer structure. Free Radic Biol Med 34(1):84–92. doi:10.​1016/​S0891-5849(02)01185-1 CrossRef
42.
go back to reference Williams RJ, Spencer JP, Rice-Evans C (2004) Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med 36:838–849CrossRef Williams RJ, Spencer JP, Rice-Evans C (2004) Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med 36:838–849CrossRef
43.
go back to reference Erlejman AG, Verstraeten SV, Fraga CG, Oteiza PI (2004) The interaction of flavonoids with membranes: potential determinant of flavonoid antioxidant effects. Free Radic Res 38(12):1311–1320. doi:10.1080/10715760400016105 CrossRef Erlejman AG, Verstraeten SV, Fraga CG, Oteiza PI (2004) The interaction of flavonoids with membranes: potential determinant of flavonoid antioxidant effects. Free Radic Res 38(12):1311–1320. doi:10.​1080/​1071576040001610​5 CrossRef
44.
go back to reference Da Silva M, Jaggers GK, Verstraeten SV, Erlejman AG, Fraga CG, Oteiza PI (2012) Large procyanidins prevent bile-acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells. Free Radic Biol Med 52(1):151–159. doi:10.1016/j.freeradbiomed.2011.10.436 CrossRef Da Silva M, Jaggers GK, Verstraeten SV, Erlejman AG, Fraga CG, Oteiza PI (2012) Large procyanidins prevent bile-acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells. Free Radic Biol Med 52(1):151–159. doi:10.​1016/​j.​freeradbiomed.​2011.​10.​436 CrossRef
45.
go back to reference Mahe S, Huneau JF, Marteau P, Thuillier F, Tome D (1992) Gastroileal nitrogen and humans. Am J Clin Nutr 56:410–441 Mahe S, Huneau JF, Marteau P, Thuillier F, Tome D (1992) Gastroileal nitrogen and humans. Am J Clin Nutr 56:410–441
48.
go back to reference Ruiz PA, Haller D (2006) Functional diversity of flavonoids in the inhibition of the proinflammatory NF-kappaB, IRF, and Akt signaling pathways in murine intestinal epithelial cells. J Nutr 136(3):664–671 Ruiz PA, Haller D (2006) Functional diversity of flavonoids in the inhibition of the proinflammatory NF-kappaB, IRF, and Akt signaling pathways in murine intestinal epithelial cells. J Nutr 136(3):664–671
49.
go back to reference Romier B, Van De Walle J, During A, Larondelle Y, Schneider YJ (2008) Modulation of signalling nuclear factor-kB activation pathway by polyphenols in human intestinal Caco-2 cells. Br J Nutr 100:542–551. doi:10.1017/S0007114508966666 CrossRef Romier B, Van De Walle J, During A, Larondelle Y, Schneider YJ (2008) Modulation of signalling nuclear factor-kB activation pathway by polyphenols in human intestinal Caco-2 cells. Br J Nutr 100:542–551. doi:10.​1017/​S000711450896666​6 CrossRef
50.
go back to reference Sergent T, Piront N, Meurice J, Toussaint O, Schneider YJ (2010) Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium. Chem Biol Interact 188(3):659–667. doi:10.1016/j.cbi.2010.08.007 CrossRef Sergent T, Piront N, Meurice J, Toussaint O, Schneider YJ (2010) Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium. Chem Biol Interact 188(3):659–667. doi:10.​1016/​j.​cbi.​2010.​08.​007 CrossRef
51.
go back to reference Seibel J, Molzberger AF, Hertrampf T, Laudenbach-Leschowski U, Diel P (2009) Oral treatment with genistein reduces the expression of molecular and biochemical markers of inflammation in a rat model of chronic TNBS-induced colitis. Eur J Nutr 48(4):213–220. doi:10.1007/s00394-009-0004-3 CrossRef Seibel J, Molzberger AF, Hertrampf T, Laudenbach-Leschowski U, Diel P (2009) Oral treatment with genistein reduces the expression of molecular and biochemical markers of inflammation in a rat model of chronic TNBS-induced colitis. Eur J Nutr 48(4):213–220. doi:10.​1007/​s00394-009-0004-3 CrossRef
Metadata
Title
Sicilian pistachio (Pistacia vera L.) nut inhibits expression and release of inflammatory mediators and reverts the increase of paracellular permeability in IL-1β-exposed human intestinal epithelial cells
Authors
C. Gentile
A. Perrone
A. Attanzio
L. Tesoriere
M. A. Livrea
Publication date
01-08-2015
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nutrition / Issue 5/2015
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-014-0760-6

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