Pomegranate extract (POMx) decreases the atherogenicity of serum and of human monocyte-derived macrophages (HMDM) in simvastatin-treated hypercholesterolemic patients: a double-blinded, placebo-controlled, randomized, prospective pilot study

Atherosclerosis. 2014 Jan;232(1):204-10. doi: 10.1016/j.atherosclerosis.2013.11.037. Epub 2013 Nov 19.

Abstract

Objective: To analyze pomegranate extract (POMx) effects on serum and on human HMDM atherogenicity in simvastatin - treated hypercholesterolemic patients.

Methods and results: Patients were randomly assigned to receive either simvastatin (20 mg/day) + vegan placebo pill (n = 11), or simvastatin (20 mg/day) + POMx pill (1g/day, n = 12). Fasting blood samples were collected at baseline and after 1 and 2 months of therapy. HMDM were collected from 3 patients in each group at baseline and after 2 months of therapy, as well as from 3 healthy subjects. After 2 months of therapy, serum LDL-cholesterol levels significantly decreased, by 23%, in the simvastatin + placebo group, and by 26% in the simvastatin + POMx group. Simvastatin + POMx therapy increased serum thiols concentration by 6%. Patients' HMDM reactive oxygen species (ROS) levels were significantly increased, by 69%, vs. healthy subjects HMDM. After 2 months of therapy, HMDM ROS levels decreased by 18% in the simvastatin + placebo group, whereas in the simvastatin + POMx group it decreased by up to 30%. A novel finding was the triglycerides levels in the patients' HMDM at baseline which were significantly higher, by 71%, vs. healthy subjects HMDM. The simvastatin + POMx, but not the simvastatin + placebo therapy, significantly reduced macrophage triglycerides content by 48%, vs. baseline levels. In addition, whereas the simvastatin + placebo therapy significantly decreased the patients' HMDM cholesterol biosynthesis rate by 33%, the simvastatin + POMx therapy further decreased it, by 44%.

Conclusion: The addition of POMx to simvastatin therapy in hypercholesterolemic patients improved oxidative stress and lipid status in the patient's serum and in their HMDM. These anti-atherogenic effects could reduce the risk for atherosclerosis development.

Keywords: Cholesterol; Hypercholesterolemia; Macrophages; Oxidative stress; Pomegranate; Triglyceride.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Animals
  • Atherosclerosis / blood
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / prevention & control
  • Cell Line
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Double-Blind Method
  • Drug Synergism
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy*
  • Leukocytes, Mononuclear / cytology
  • Lipids / blood
  • Lythraceae / chemistry
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Male
  • Mice
  • Middle Aged
  • Monocytes / drug effects*
  • Oxidative Stress
  • Oxygen / chemistry
  • Pilot Projects
  • Plant Extracts / administration & dosage*
  • Prospective Studies
  • Reactive Oxygen Species
  • Simvastatin / administration & dosage*
  • Triglycerides / blood

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Plant Extracts
  • Reactive Oxygen Species
  • Triglycerides
  • Simvastatin
  • Oxygen