Metabolites of the ellagitannin, geraniin inhibit human ACE; in vitro and in silico evidence

Int J Food Sci Nutr. 2021 Jun;72(4):470-477. doi: 10.1080/09637486.2020.1830263. Epub 2020 Oct 9.

Abstract

Hypertension is defined as the persistence of elevated blood pressure in the circulation system. The renin-angiotensin-aldosterone system is a major modulator of blood pressure. Among the risk factors of cardiovascular disease, hypertension is the most preventable and treatable, with drugs such as ACE inhibitors. Many ACE inhibitors are known to have undesirable side effects and hence, natural alternatives are being sought. Dietary polyphenols, particularly ellagitannins, are derived from plant products and are known to exhibit a variety of bioactivities. Geraniin, an ellagitannin has been shown to have antihypertensive activity in animal experiments. It is speculated that the metabolites of geraniin are responsible for its ACE inhibitory activity. We have performed in vitro ACE inhibition and in silico studies with geraniin and its metabolites (ellagic acid, urolithins). Our studies confirm that ellagic acid exhibited similar inhibitory potential to ACE as the positive control captopril.

Keywords: ACE; ellagic acid; ellagitannin geraniin; hypertension; urolithin.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure / drug effects
  • Carboxypeptidases / drug effects*
  • Computer Simulation
  • Coumarins
  • Ellagic Acid / metabolism
  • Ellagic Acid / pharmacology
  • Ellagic Acid / therapeutic use
  • Glucosides / metabolism*
  • Humans
  • Hydrolyzable Tannins / metabolism*
  • Hypertension / drug therapy
  • Molecular Docking Simulation
  • Peptidyl-Dipeptidase A / drug effects
  • Polyphenols / pharmacology
  • Rabbits

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Coumarins
  • Glucosides
  • Hydrolyzable Tannins
  • Polyphenols
  • ellagitannin
  • Ellagic Acid
  • Geraniin
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • Angiotensin-Converting Enzyme 2