Skip to main content Accessibility help

Ellagic acid inhibits IL-1β-induced cell adhesion molecule expression in human umbilical vein endothelial cells

  • Ya-Mei Yu (a1), Zhi-Hong Wang (a1), Chung-Hsien Liu (a2) and Chin-Seng Chen (a3)


Expression of cell adhesion molecules by endothelium and the attachment of monocytes to endothelium may play a major role in atherosclerosis. Ellagic acid (EA) is a phenolic compound found in fruits and nuts including raspberries, strawberries, grapes and walnuts. Previous studies have indicated that EA possesses antioxidant activity in vitro. In the present study, we investigated the effects of EA on the formation of intracellular reactive oxygen species, the translocation of NFκB and expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 and endothelial leucocyte adhesion molecule (E-selectin) induced by IL-1β in human umbilical vein endothelial cells (HUVEC). We found that EA significantly reduced the binding of human monocytic cell line, U937, to IL-1β-treated HUVEC. The production of reactive oxygen species by IL-1β was dose-dependently suppressed by EA. Supplementation with increasing doses of EA up to 50 μmol/l was most effective in inhibiting the expression of VCAM-1 and E-selectin. Furthermore, the inhibition of IL-1β-induced adhesion molecule expression by EA was manifested by the suppression of nuclear translocation of p65 and p50. In conclusion, EA inhibits IL-1β-induced nuclear translocation of p65 and p50, thereby suppressing the expression of VCAM-1 and E-selectin, resulting in decreased monocyte adhesion. Thus, EA has anti-inflammatory properties and may play an important role in the prevention of atherosclerosis.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Ellagic acid inhibits IL-1β-induced cell adhesion molecule expression in human umbilical vein endothelial cells
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Ellagic acid inhibits IL-1β-induced cell adhesion molecule expression in human umbilical vein endothelial cells
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Ellagic acid inhibits IL-1β-induced cell adhesion molecule expression in human umbilical vein endothelial cells
      Available formats


Corresponding author

* Corresponding author: Dr Ya-Mei Yu, fax +886 4 22083762, email


Hide All
Baeuerle, PA (1991) The inducible transcription activator NFκB: regulation by distinct protein subunits. Biochim Biophys Acta 1072, 6380.
Baeuerle, PA & Baltimore, D (1988) IκB: a specific inhibitor of the NFκB transcription factor. Science 242, 540546.
Baeuerle, PA & Henkel, T (1994) Function and activation of NF-κB in the immune system. Annu Rev Immunol 12, 141179.
Barnes, PJ & Karin, M (1997) Nuclear factor-kappa B: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336, 10661071.
Bass, DA, Parce, JW, Decharelet, LR, Szejda, P, Seeds, MC & Thomas, M (1983) Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J Immunol 130, 19101917.
Brand, K, Page, S, Rogler, G, Bartsch, A, Brandl, R, Knuechel, R, Page, M, Kalschmidt, C, Baeuerle, PA & Neumeier, D (1996) Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J Clin Invest 97, 17151722.
Chen, YH, Lin, SJ, Chen, JW, Ku, HH & Chen, YL (2002) Magnolol attenuates VCAM-1 expression in vitro in TNF-α-treated human aortic endothelial cells and in vivo in the aorta of cholesterol-fed rabbits. Br J Pharmacol 135, 3747.
Chenbg, Q, Cant, CA, Moll, T, Hofer-Warbinek, R, Wagner, E, Birnstiel, ML, Bach, FH & de Martin, R (1994) NF-κB subunit-specific regulation of the I kappa B-alpha promoter. J Biol Chem 296, 1355113557.
Collins, T (1993) Biology of disease: endothelial nuclear factor-κB and the initiation of the atherosclerotic lesion. Lab Invest 68, 499508.
Cozzi, R, Ricordy, R, Bartolini, F, Ramadori, L, Perticone, P & De Salvia, R (1995) Taurine and ellagic acid: two differently-acting natural antioxidants. Environ Mol Mutagen 26, 248254.
Cybulsky, MA & Gimbrone, J (1991) Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 251, 788791.
Cybulsky, MI, Iiyama, K, Li, H, Zhu, S, Chen, M, Liyama, M, Davis, V, Gutierrez-Ramos, JC, Connelly, PW & Milstone, DS (2001) A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest 107, 12551262.
D'Acquisto, F, May, MJ & Ghosh, S (2002) Inhibition of nuclear factor kappa B (NF-κB): an emerging theme in anti-inflammatory therapies. Mol Intervent 2, 2235.
de Ancos, B, Gonzalez, EM & Cano, MP (2000) Ellagic acid, vitamin C and total phenolic contents and radical scavenging capacity affected by freezing and frozen storage in raspberry fruit. J Agric Food Chem 48, 45654570.
Dschietzig, T, Richter, C, Pfannenschmidt, G, Bartsch, C, Laule, M, Baumann, G & Stangl, K (2001) Dexamethasone inhibits stimulation of pulmonary endothelins by proinflammatory cytokines: possible involvement of a nuclear factor κB dependent mechanism. Intensive Care Med 27, 751756.
Gaziano, JM, Manson, J, Buring, JE & Hennekens, CH (1992) Dietary antioxidants and cardiovascular disease. Ann N Y Acad Sci 669, 249259.
Gey, KF, Stahelin, HB & Eichholser, M (1993) Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: Panel Prospective Study. J Clin Invest 71, 36.
Grilli, M, Chiu, JJS & Lenardo, MJ (1993) NFκB and Rel: participants in a multiform transcriptional regulatory system. Int Rev Cytol 143, 162.
Hiscott, J, Marois, J, Garoufalis, J, et al. (1993) Characterization of a functional NF-kappa B site in the human interleukin-1β promoter: evidence for a positive autoregulatory loop. Mol Cell Biol 13, 62316240.
Iino, T, Nakahara, K, Miki, W, Kiso, Y, Ogawa, Y, Kato, S & Takeuchi, K (2001) Less damaging effect of whisky in rat stomachs in comparison with pure ethanol. Role of ellagic acid, the nonalcoholic component. Digestion 64, 214221.
Islam, KN, Devaraj, S & Jialal, I (1998) alpha-Tocopherol enrichment of monocytes decrease agonist-induced adhesion to human endothelial cells. Circulation 98, 22552261.
Laranjinha, J, Vierira, O, Almeida, L & Madeira, V (1996) Inhibition of metmyoglobin/H2O2-dependent low density lipoprotein lipid peroxidation by naturally occurring phenolic acid. Biochem Pharmacol 51, 395402.
Li, X & Wang, X (2002) Application of real-time polymerase chain reaction for the quantitation of interleukin-1β mRNA upregulation in brain ischemic tolerance. Brain Res Protocols 5, 211217.
Ludwig, A, Lorenz, M, Grimbo, N, Steinle, F, Meiners, S, Bartsch, C, Stangl, K, Baumann, G & Stangl, V (2004) The tea flavonoid epigallocatechin-3-gallate reduces cytokine-induced VCAM-1 expression and monocyte adhesion to endothelial cells. Biochem Biophys Res Commun 316, 659665.
Martin, A, Foxall, T, Blumberg, JB & Meydani, M (1997) Vitamin E inhibits low density lipoprotein-induced adhesion of monocytes to human aortic endothelial cells in vitro . Arterioscler Thromb Vasc Biol 17, 429436.
Mertens-Talcott, SU, Talcott, ST & Percival, SS (2003) Low concentrations of Quercetin and ellagic acid synergistically influence proliferation, cytotoxicity and apoptosis in MOLT-4 human leukemia cells. J Nutr 133, 26692674.
Muller, JM, Rupec, RA & Baeuerle, PA (1997) Study of gene regulation by NF-kappa B and AP-1 in response to reactive oxygen intermediates. Methods 11, 301312.
Neish, AS, Williams, AJ, Palmer, HJ, Whitley, MZ & Clollins, T (1992) Functional analysis of the human vascular cell adhesion molecule-1 promoter. J Exp Med 176, 15831593.
Poston, RN, Haskard, DO, Coucher, JR, Gall, NP & Johnson-Tidey, RR (1992) Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. Am J Pathol 140, 665673.
Qwarnstrom, EE, Ostberg, CO, Turk, GL, Richardson, CA & Bomsztyk, K (1994) Fibronectin attachment activates the NF-κB p50/p65 heterodimer in fibroblasts and smooth muscle cells. J Biol Chem 269, 3076530768.
Rohde, LE, Lee, RT, Rivero, J, Jamacochian, M, Arroyo, LH, Briggs, W, Rifai, N, Libby, P, Creager, MA & Ridker, PM (1998) Circulating cell adhesion molecules are correlated with ultrasound-based assessment of carotid atherosclerosis. Arterioscler Thromb Vasc Biol 18, 17651770.
Ross, R (1999) Atherosclerosis is an inflammatory disease. Am Heart J 138, S419S420.
Sellappan, S, Akoh, CC & Krewer, G (2002) Phenolic compounds and antioxidant capacity of Georgia-grown blueberries and blackberries. J Agric Food Chem 50, 24322438.
Stangl, V, Gunther, A, Jarrin, A, Bramlage, P, Moobed, M, Staudt, A, Baumann, G & Stangl, K (2001) Homocysteine inhibits TNF-alpha-induced endothelial adhesion molecule expression and monocyte adhesion via nuclear factor-κB dependent pathway. Biochem Biophys Res Commun 280, 10931100.
Walgren, RA, Walle, UK & Walle, T (1998) Transport of quercetin and its glucosides across human intestinal epithelial Caco-2 cells. Biochem Pharmacol 55, 17211727.
Whitley, AC, Stoner, GD, Darby, MV & Walle, T (2003) Intestinal epithelial cell accumulation of the cancer preventive polyphenol ellagic acid – extensive binding to protein and DNA. Biochem Pharmacol 66, 907915.
Yu, YM, Chang, WC, Wu, CH & Chiang, SY (2005) Reduction of oxidative stress and apoptosis in hyperlipidemic rabbits by ellagic acid. J Nutr Biochem 16, 675681.
Zapolska-Downar, D, Zapolski-Downar, A, Markiewski, M, Diechanowicz, A, Kaczmarczyk, M & Naruszewicz, M (2001) Selective inhibition by probucol of vascular cell adhesion molecule-1 (VCAM-1) expression in human vascular endothelial cells. Atherosclerosis 155, 123130.
Zhou, Z, Liu, Y, Miao, AD & I Wang, SQ (2005) Protocatechuic aldehyde suppresses TNF-α-induced ICAM-1 and VCAM-1 expression in human umbilical vein endothelial cells. Eur J Pharmacol 513, 18.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed