The interaction of tea ¯avonoids with the NO-system: discrimination between good and bad NO Chantal G.M. Heijnen a, *, Guido R.M.M. Haenen a , Sheila A. Wiseman b , Lilian B.M. Tijburg b , Aalt Bast a a Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands b Unilever Research, PO Box 114, 3130 AC Vlaardingen, The Netherlands Received 12 August 1999; received in revised form 2 February 2000; accepted 11 February 2000 Abstract The eect of black and green tea on the NO system was tested. Beside a general eect i.e. NO scavenging, the teas interacted with good, i.e. relaxation of the aorta, and bad eects, i.e. peroxynitrite scavenging, of NO. Green tea was a better NO and peroxynitrite scavenger than black tea. Epigallocatechin gallate was the major identi®ed contributor to both the peroxynitrite and NO scaven- ging. The thea¯avins, only present in black tea, also had a substantial contribution to the NO scavenging of black tea. The teas were found to have only a minor and nonspeci®c eect on the NO mediated vasorelaxation. Based on these results it is concluded that tea discriminates between the good and bad eects of NO; tea is likely to prevent NO toxicity primarily. # 2000 Elsevier Science Ltd. All rights reserved. Keywords: Flavonoid; Black tea; Green tea; NO scavenging; Peroxynitrite scavenging 1. Introduction Nitric oxide (nitrogen monoxide, NO) plays an ambiguous role in physiology. On the one hand NO is involved in various regulatory processes as second mes- senger. For example, the acetylcholine-induced relaxa- tion in aorta is NO-mediated. Upon stimulation of the acetylcholine-receptor, the constitutive NO-synthase (NOS) produces NO. NO activates guanylate cyclase, which leads to the production of cyclic GMP, and ulti- mately to vasorelaxation. On the other hand NO is toxic, predominantly due to the formation of peroxyni- trite formed in the reaction with superoxide radicals (Radi, Beckman, Bush & Freeman, 1991; Rubbo, Darley- Usmar & Freeman, 1996). Previously, it has been shown that ¯avonoids, i.e. a group of polyphenolic antioxidants (Miller, Cas- telluccio, Tijburg & Rice-Evans, 1996; Salah, Miller, Paganga, Tijburg, Bolwell & Rice-Evans, 1995), interact with the NO system. For example, it has been found that ¯avonoids are ecient scavengers of the nitric oxide radical (Haenen & Bast, 1999; Verhagen, Haenen & Bast, 1996). In their eect on the NO system, e.g. NO scavenging, the ¯avonoids do not distinguish between good and bad NO. It has been reported that ¯avonoids accumulate in vascular tissue between the endothelial layer and the vascular smooth muscle cells (Neu- mann, Carlsson & Brom, 1992). Interestingly at this site both bene®cial (vasorelaxation) and detrimental (atherosclerosis) processes with NO as a protagonist take place. A major source of ¯avonoids in the western diet is tea (Camellia sinensis). The most frequently consumed teas are black and green tea. In the production of green tea, steaming and drying of the tealeaves prevent oxidation of the polyphenols in the leaves. The major polyphenols of green tea are catechins, mainly epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG). In the production of black tea fermentation, i.e. enzymatic, aerobic oxidation of leaf polyphenols, and subsequent condensation, takes place. Due to this pro- cess, the total catechin content is reduced to approxi- mately 20% of the total catechin content of green tea, and new products, such as thea¯avins, are formed. The thea¯avins comprise approximately 1% of the total ¯a- vonoids of black tea. The major ones are thea¯avin, 0308-8146/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. PII: S0308-8146(00)00105-9 Food Chemistry 70 (2000) 365±370 www.elsevier.com/locate/foodchem * Corresponding author. Tel.: +31-43-38811388/417; fax: +31-43- 3884149. E-mail address: C.Heijnen@farmaco.unimaas.nl (C.G.M. Heijnen).