Evaluating the effects of phenolics from Phagnalon rupestre (L.) DC on cellular nitration and oxidation

Not only do reactive nitrogen species modify proteins and nucleotides by means of oxidative or nitrating reactions, but they can also cause other structural alterations which have a physiopathological significance in a number of human diseases. Given that some naturally occurring phenolics, such as hydroxycinnamate and hydroxybenzoate derivatives, are particularly effective at preventing the degradation of biomolecules, such compounds should actually protect against these unfavourable conditions. The present communication describes our ongoing investigations of three phenolics isolated from Phagnalon rupestre (Asteraceae): 2-isoprenylhydroquinone-1-glucoside (IHG), 3,5-dicaffeoylquinic acid (DCA) and its methyl ester (DCE) [1], previously described as peroxynitrite-scavengers for free tyrosine [2], on nitrating and oxidative reactions in two different cellular systems. We examined the effect of these compounds on bovine seroalbumin nitration by human neutrophils [3] and on dihydrorhodamine 123 (DHR 123) oxidation in macrophages [4], both stimulated with tetradecanoylphorbol acetate. All the compounds tested significantly reduced protein-bound tyrosine nitration in neutrophils with IC₅₀ values of 27.9, 10.5, 11.0 and 20.7 microM for IHG, DCA, DCE and the reference epigallocatechin gallate (EGCG), respectively. DCE was the most active compound in preventing DHR 123 oxidation with 46 and 61% inhibition at 50 and 100 microM, respectively. Since caffeoylquinic derivatives have previously been described as human leukocyte myeloperoxidase (MPO) inhibitors [5], this may have an influence on their ability to impair the formation of the nitrating agent NO₂, which is generated by MPO in the neutrophils. Because of their phenolic nature, such compounds should manifest noteworthy antioxidant activity; however, they do not behave uniformly in preventing DHR 123 oxidation.

Acknowledgements: A.O. is recipient of a grant from Generalitat Valenciana. This work was supported by the Spanish Ministry of Science and Technology (SAF 2002–00723).

References: 1. Góngora, L. et al. (2002), Planta Med. 68: 561–564. 2. Olmos, A. et al. (2005), Nitric Oxide 12: 54–60. 3. Eiserich, J.P. et al. (1998), Nature 391: 393–397. 4. Walrand, S. et al. (2003), Clin. Chim. Acta 331: 103–110. 5. Góngora, L. et al. (2002), Life Sci. 71: 2995–3004.