Ellagic acid and its methyl-derivatives inhibit a newly found nitratase activity

• Published in: Fundamental & clinical pharmacology Vol. 24; no. 1; pp. 115 - 119
• Main Authors: Léger, Claude L., Torres-Rasgado, Enrique, Fouret, Gilles, Lauret, Céline, Carbonneau, Marie-Annette
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2010; Blackwell
• Subjects: albumin; Beverages; Biological and medical sciences; Blood Proteins - metabolism; denitrating activity; Ellagic Acid - analogs & derivatives; Ellagic Acid - chemistry; Ellagic Acid - pharmacology; Fruit - chemistry; Humans; In Vitro Techniques; Lipoproteins - metabolism; low density lipoprotein; Medical sciences; nitratase; Oxidoreductases - antagonists & inhibitors; peroxynitrite; Pharmacology. Drug treatments; polyphenol; Serum Albumin - metabolism; Antineoplastic agent; low density lipoprotein; peroxynitrite; Hemostatic; Antimutagen; Albumin; nitratase; Biological activity; Lipoprotein LDL; Polyphenol; denitrating activity; Ellagic acid; Phenols; Inhibitor
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/j.1472-8206.2009.00734.x

We have recently shown that low density lipoprotein (LDL) was able to denitrate albumin‐bound 3‐NO2‐Tyr residues and to concomitantly release NO3− through a Ca2+‐dependent process that has been ascribed to a specific protein structure. A lipophilic food component (γ‐tocopherol), which is easily loaded into LDL has been found to totally inhibit denitrating activity. We presently found that ellagic acid (EA) and its methylated derivatives, 4,4′O‐methyl‐ and 3,3′O‐methyl‐ellagic acids (MeEA1 and MeEA2, respectively), amphipathic phenolic components of certain fruits and beverages, were also able to inhibit this activity, with a total inhibition for EA and a 60% inhibition for MeEA1 and MeEA2. EA exhibited the highest affinity for protein plasma, whereas a higher affinity of MeEA1 and MeEA2 (with MeEA1 > MeEA2) than EA was found for lipoprotein fractions, suggesting that the inhibition‐driving property is protein affinity. As a result of this nitratase‐inhibition property EA and its natural metabolite MeEA2 may have a beneficial role in special physiopathological conditions.