Pine bark extract prevents low-density lipoprotein oxidation and regulates monocytic expression of antioxidant enzymes

Nutr Res. 2015 Jan;35(1):56-64. doi: 10.1016/j.nutres.2014.10.010. Epub 2014 Oct 20.


Polyphenols are widely distributed in leaves, seeds, bark, and flowers and considered to have beneficial effects on cardiovascular health. We hypothesized that the potent antioxidant properties of pine bark extract (PBE) are exerted by its ability to scavenge free radicals and induce antioxidant enzymes. Therefore, we investigated the effects of PBE on low-density lipoprotein (LDL) oxidation and the antioxidant defense system in monocytes. Oxidative susceptibility of LDL was determined by lag time assay in vitro and by using a human umbilical vein endothelial cell-mediated oxidation model. THP-1 monocytic cells were treated with PBE, and the expression of antioxidant enzymes was measured by real-time polymerase chain reaction and Western blot. Pine bark extract showed radical scavenging ability and significantly inhibited free radical-induced and endothelial cell-mediated LDL oxidation in vitro. Pine bark extract treatment resulted in increases in the expressions of antioxidant enzymes, glutathione peroxidase-1, catalase, and heme oxygenase-1 in THP-1 cells. In addition, PBE induced nuclear factor-erythroid-2-related factor 2 activation, which was accompanied by the activation of extracellular signal-regulated kinase and Akt despite a down-regulation of reactive oxygen species. After the monocyte investigations, we further examined the antioxidant effect after the intake of PBE by 10 healthy male volunteers. Pine bark extract significantly prolonged the lag time of LDL oxidation. Based on our findings, it appears that PBE enhances the antioxidant defense capacity of LDL and monocytes and may play a preventive role in atherosclerosis progression.

Keywords: Antioxidant; Lipid peroxidation; Monocytes; NF-E2–related factor 2; Pine bark extract; Polyphenol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Atherosclerosis / prevention & control
  • Catalase / genetics
  • Cell Line
  • Down-Regulation
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Glutathione Peroxidase GPX1
  • Healthy Volunteers
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Lipoproteins, LDL / metabolism*
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Pinus / chemistry*
  • Plant Bark / chemistry
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Real-Time Polymerase Chain Reaction


  • Antioxidants
  • Lipoproteins, LDL
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Plant Extracts
  • Reactive Oxygen Species
  • Catalase
  • Glutathione Peroxidase
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Extracellular Signal-Regulated MAP Kinases
  • Glutathione Peroxidase GPX1