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

Fundam Clin Pharmacol. 2010 Feb;24(1):115-9. doi: 10.1111/j.1472-8206.2009.00734.x. Epub 2009 Aug 12.

Abstract

We have recently shown that low density lipoprotein (LDL) was able to denitrate albumin-bound 3-NO(2)-Tyr residues and to concomitantly release NO(3)(-) through a Ca(2+)-dependent process that has been ascribed to a specific protein structure. A lipophilic food component (gamma-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.

Publication types

  • Comparative Study

MeSH terms

  • Beverages
  • Blood Proteins / metabolism
  • Ellagic Acid / analogs & derivatives*
  • Ellagic Acid / chemistry
  • Ellagic Acid / pharmacology*
  • Fruit / chemistry
  • Humans
  • In Vitro Techniques
  • Lipoproteins / metabolism
  • Oxidoreductases / antagonists & inhibitors*
  • Serum Albumin / metabolism

Substances

  • 3,3'-O-methylellagic acid
  • 4,4'-O-methylellagic acid
  • Blood Proteins
  • Lipoproteins
  • Serum Albumin
  • Ellagic Acid
  • Oxidoreductases
  • nitratase