Frontiers in Pharmacology (Feb 2011)

Hyperforin, an anti-inflammatory constituent from St. John’s wort, inhibits microsomal prostaglandin E2 synthase-1 and suppresses prostaglandin E2 formation in vivo

  • Andreas eKoeberle,
  • Andreas eKoeberle,
  • Antonietta eRossi,
  • Julia eBauer,
  • Friederike eDehm,
  • Luisella eVerotta,
  • Hinnak eNorthoff,
  • Lidia eSautebin,
  • Oliver eWerz

DOI
https://doi.org/10.3389/fphar.2011.00007
Journal volume & issue
Vol. 2

Abstract

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The acylphloroglucinol hyperforin (Hyp) from St. John’s wort possesses anti-inflammatory and anti-carcinogenic properties which were ascribed among others to the inhibition of 5-lipoxygenase. Here, we investigated whether Hyp also interferes with prostanoid generation in biological systems, particularly with key enzymes participating in prostaglandin (PG)E2 biosynthesis, i.e., cyclooxygenases (COX)-1/2 and microsomal PGE2 synthase (mPGES)-1 which play key roles in inflammation and tumorigenesis. Similar to the mPGES-1 inhibitors MK-886 and MD-52, Hyp significantly suppressed PGE2 formation in whole blood assays starting at 0.03 to 1 µM, whereas the concomitant generation of COX-derived 12(S)-hydroxy-5-cis-8,10-trans-hepta¬deca¬trienoic acid, thromboxane B2, and 6-keto PGF1α was not significantly suppressed up to 30 µM. In cell-free assays, Hyp efficiently blocked the conversion of PGH2 to PGE2 mediated by mPGES-1 (IC50 = 1 µM), and isolated COX enzymes were not (COX-2) or hardly (COX-1) suppressed. Intraperitoneal (i.p.) administration of Hyp (4 mg kg-1) to rats impaired exudate volume and leukocyte numbers in carrageenan-induced pleurisy associated with reduced PGE2 levels, and Hyp (given i.p.) inhibited carrageenan-induced mouse paw edema formation (ED50 = 1 mg kg-1) being superior over indomethacin (ED50 = 5 mg kg-1). We conclude that the suppression of PGE2 biosynthesis in vitro and in vivo by acting on mPGES-1 critically contributes to the anti-inflammatory efficiency of Hyp.

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