Protein tyrosine nitration is clearly established under disease conditions [1]. It is mediated by reactive nitrogen species (RNS) such as peroxynitrite and nitrite, formed as secondary products of NO metabolism in presence of oxidants including superoxide and hydrogen peroxide (H2O2). Provided that the content of some naturally occurring phenolics, such as hydroxycinnamates, in medicinal plants and dietary supplements is actually high, and taking into account the interaction with RNS [2,3], these principles have become increasingly important. The present communication reports further investigations of two phenolics, isolated from Phagnalon rupestre (Asteraceae) [4]: 3,5-dicaffeoylquinic acid (DCA) and its methyl ester (DCE), on a myoglobin-catalyzed nitration process by nitrite/hydrogen peroxide using a cell-free system [5]. Both compounds exerted a weak inhibition on the nitration of free tyrosine while the reference epigallocatechin gallate (EGCG) exhibited an IC50 value of 40µM. Additionally, in order to achieve the influence into the genesis of NO production, we examined their effect on inducible nitric oxide synthase (NOS-2) expression and nitrite levels as well as on interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) production in cultured macrophages stimulated with lipopolysaccharide (LPS) [5]. DCA and EGCG decreased the nitrite levels as well as the expression of NOS-2, while DCE showed no effect. DCE and EGCG inhibited IL-1β production by 54% and 57%, respectively, and moderately reduced the levels of TNF-α while DCA only produced a slight decrease in the level of IL-1β. The moderate inhibition of IL-1β production by DCE was scarcely detectable at the RNA message level. These results indicate that these principles are able to modulate NOS-2 activation in part via reduction of cytokine release. In contrast, they seem to be poorly efficient on peroxide-mediated tyrosine nitration.
Acknowledgements: This work was supported by the Spanish Ministry of Science and Technology (SAF 2002–00723) and by the Generalitat Valenciana (Project GV 353/06).
References: [1] Radi, R. et al. (2004) PNAS 101: 4003. [2] Olmos, A. et al. (2005) Nitric Oxide 12: 54. [3] Olmos, A. et al. (2007) Planta Med. 73: 20. [4] Góngora, L. et al. (2002) Planta Med. 68: 561. [5] Olmos, A. et al. (2007) Eur. J. Pharm. Sci. 30: 220.
