Antioxidant activity and inhibition of matrix metalloproteinases by metabolites of maritime pine bark extract (pycnogenol)

Free Radic Biol Med. 2004 Mar 15;36(6):811-22. doi: 10.1016/j.freeradbiomed.2003.12.017.

Abstract

The procyanidin-rich maritime pine bark extract Pycnogenol has well-documented antioxidant and anti-inflammatory activity. After oral administration of Pycnogenol two major metabolites are formed in vivo, delta-(3,4-dihydroxyphenyl)-gamma-valerolactone (M1) and delta-(3-methoxy-4-hydroxyphenyl)-gamma-valerolactone (M2). We elucidated the effects of these metabolites on matrix metalloproteinases (MMPs) and determined their antioxidant activity to understand their contribution to the effects of maritime pine bark extract. We discovered strong inhibitory effects of M1 and M2 toward the activity of MMP-1, MMP-2, and MMP-9. On a microgram-per-milliliter basis both metabolites appeared more active than Pycnogenol. The metabolites were more effective than their metabolic precursor (+)-catechin in MMP inhibition. On a cellular level, we detected highly potent prevention of MMP-9 release by both metabolites, with concentrations of 0.5 microM resulting in about 50% inhibition of MMP-9 secretion. M1 was significantly more effective in superoxide scavenging than (+)-catechin, ascorbic acid, and trolox, while M2 displayed no scavenging activity. Both metabolites exhibited antioxidant activities in a redox-linked colorimetric assay, with M1 being significantly more potent than all other compounds tested. Thus, our data contribute to the comprehension of Pycnogenol effects and provide a rational basis for its use in prophylaxis and therapy of disorders related to imbalanced or excessive MMP activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Flavonoids / metabolism
  • Flavonoids / pharmacology*
  • Free Radical Scavengers / metabolism
  • Humans
  • Lactones / pharmacology
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases / metabolism*
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Nitroblue Tetrazolium / chemistry
  • Nitroblue Tetrazolium / metabolism
  • Plant Extracts
  • Protein Binding
  • Superoxides / antagonists & inhibitors
  • Zinc / metabolism
  • Zinc / pharmacology

Substances

  • Antioxidants
  • Enzyme Inhibitors
  • Flavonoids
  • Free Radical Scavengers
  • Lactones
  • Matrix Metalloproteinase Inhibitors
  • Plant Extracts
  • delta(3,4-dihydroxyphenyl)-gamma-valerolactone
  • delta(3-methoxy-4-hydroxyphenyl)-gamma-valerolactone
  • Superoxides
  • Nitroblue Tetrazolium
  • pycnogenols
  • Matrix Metalloproteinases
  • Zinc