Nitric Oxide 15 (2006) 259–263 www.elsevier.com/locate/yniox 1089-8603/$ - see front matter  2005 Elsevier Inc. All rights reserved. doi:10.1016/j.niox.2005.12.004 Brief communication Pomegranate juice reduces oxidized low-density lipoprotein downregulation of endothelial nitric oxide synthase in human coronary endothelial cells Filomena de Nigris a , Sharon Williams-Ignarro b , Chiara Botti a , Vincenzo Sica a , Louis J. Ignarro c , Claudio Napoli a,¤ a Department of General Pathology and Excellence Research Center on Cardiovascular Disease, University of Naples, Italy b Anesthesiology Division, University of California at Los Angeles, Los Angeles, USA c Pharmacology Division, University of California at Los Angeles, Los Angeles, USA Received 16 September 2005; revised 9 December 2005 Available online 18 January 2006 Abstract We examined the hypothesis that pomegranate juice (PJ) can revert the potent downregulation of the expression of endothelial nitric- oxide synthase (NOSIII) induced by oxidized low-density liporotein (oxLDL) in human coronary endothelial cells. Western blot and Northern blot analyses showed a signiWcant decrease of NOSIII expression after a 24-h treatment with oxLDL. Accordingly, we observed a signiWcant dose-dependent reduction in nitric oxide bioactivity represented by both basal and bradykinin-stimulated cellular cGMP accumulation. These phenomena were corrected signiWcantly by the concomitant treatment with PJ. Our data suggest that PJ can exert beneWcial eVects on the evolution of clinical vascular complications, coronary heart disease, and atherogenesis in humans by enhancing the NOSIII bioactivity.  2005 Elsevier Inc. All rights reserved. Keywords: Nitric oxide; eNOS; Pomegranate juice Pomegranate juice (PJ) is rich in antioxidants of the polyphenolic Xavonoid class, which includes tannins and anthocyanins. These antioxidants are more potent, on a molar basis, than many other antioxidants including vita- min C, vitamin E, coenzyme Q-10 and alpha-lipoic acid. The antioxidant level in PJ was found to be higher than that in other natural juices, and red wine [1]. Antioxidants in general possess numerous important biological properties including protection against choles- terol oxidation, protection against atherogenesis, anti- inXammatory eVects, anti-aging eVects, and protection against Alzheimer’s disease and diabetes. Atherosclerosis is responsible for myocardial infarctions and ischemic strokes and is characterized by a long lag-time between onset and clinical manifestation. Work by a number of investigators over the last 10–15 years has demonstrated that modiWca- tions of lipoproteins, resulting from oxidative stress and other processes may play an important pathogenic role in atherosclerosis [2,3]. Conditions known as “classical risk factors” such as hypertension, diabetes, and menopause all increase in frequency with advancing age and may contrib- ute both directly and indirectly to lipoprotein modiWcation and vascular injury [3–5]. Indeed, one important conse- quence of this may be enhanced susceptibility of lipopro- teins to oxidation. Moreover, a plethora of additional detrimental oxidation-sensitive mechanisms can increase during hypercholesterolemia [5,6]. Biochemical modiWcations of low-density lipoprotein (LDL) aVecting its composition can greatly enhance the injurious potential of LDL and its involvement in the path- ogenesis of various disease states [2,3,5,6]. Indeed, oxidized * Corresponding author. E-mail addresses: claunap@tin.it, claunap@bu.edu (C. Napoli).