Paradoxical effects of resveratrol on the two prostaglandin H synthases

Prostaglandins Other Lipid Mediat. 1998 Jun;56(2-3):131-43. doi: 10.1016/s0090-6980(98)00052-5.


Prostaglandin H synthase (PGHS) is the primary enzyme responsible for the biosynthesis of prostaglandins and thromboxanes. Of the two isoenzymes of PGHS, PGHS-1 is constitutively expressed and PGHS-2 is inducible by mitogens or other inflammatory stimuli. Constitutive expression of PGHS-2 in neoplastic tissues has been implicated in carcinogenesis. Resveratrol, a lignan, was recently shown to be an anticarcinogen that selectively inhibits PGHS-1. In vitro experiments to resolve these seemingly paradoxical observations revealed that resveratrol is not only an inhibitor of PGHS-1 but also is an activator of PGHS-2. Resveratrol non-competitively inhibited PGHS-1 with a K1 of 26 +/- 2 microM but enhanced the PGHS-2 activity nearly twofold. Additionally, resveratrol did not serve as a reducing co-substrate for the peroxidase activities of either enzyme despite being an easily oxidizable phenolic compound. Resveratrol inhibited the peroxidase activity of PGHS-1 (IC50 = 15 microM) better than that of PGHS-2 (IC50 = > 200 microM). Inhibition of the perxidase activity but not the cyclooxygenase activity of PGHS-2 resulted in the production of PGG2 from arachidonic acid. A plausible relationship between these observation and the anticarcinogenic activity of resveratrol is discussed.

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • Chromatography, High Pressure Liquid
  • Cyclooxygenase Inhibitors / pharmacology*
  • Enzyme Activation / drug effects
  • Female
  • Indomethacin / pharmacology
  • Isoenzymes / antagonists & inhibitors*
  • Male
  • Oxidation-Reduction
  • Phenol / pharmacology
  • Prostaglandin H2
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Prostaglandins G / biosynthesis
  • Prostaglandins H / biosynthesis
  • Resveratrol
  • Sheep
  • Stilbenes / pharmacology*


  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Prostaglandins G
  • Prostaglandins H
  • Stilbenes
  • Arachidonic Acid
  • Phenol
  • Prostaglandin H2
  • prostaglandin G2
  • Prostaglandin-Endoperoxide Synthases
  • Resveratrol
  • Indomethacin