Inhibition of microsomal prostaglandin E2 synthase-1 as a molecular basis for the anti-inflammatory actions of boswellic acids from frankincense.

Frankincense, the gum resin derived from Boswellia species, showed anti-inflammatory efficacy in animal models and in pilot clinical studies. Boswellic acids (BAs) are assumed to be responsible for these effects but their anti-inflammatory efficacy in vivo and their molecular modes of action are incompletely understood.
A protein fishing approach using immobilized BA and surface plasmon resonance (SPR) spectroscopy were used to reveal microsomal prostaglandin E(2) synthase-1 (mPGES1) as a BA-interacting protein. Cell-free and cell-based assays were applied to confirm the functional interference of BAs with mPGES1. Carrageenan-induced mouse paw oedema and rat pleurisy models were utilized to demonstrate the efficacy of defined BAs in vivo.
Human mPGES1 from A549 cells or in vitro-translated human enzyme selectively bound to BA affinity matrices and SPR spectroscopy confirmed these interactions. BAs reversibly suppressed the transformation of prostaglandin (PG)H(2) to PGE(2) mediated by mPGES1 (IC(50) = 3-10 µM). Also, in intact A549 cells, BAs selectively inhibited PGE(2) generation and, in human whole blood, β-BA reduced lipopolysaccharide-induced PGE(2) biosynthesis without affecting formation of the COX-derived metabolites 6-keto PGF(1α) and thromboxane B(2) . Intraperitoneal or oral administration of β-BA (1 mg·kg(-1) ) suppressed rat pleurisy, accompanied by impaired levels of PGE(2) and β-BA (1 mg·kg(-1) , given i.p.) also reduced mouse paw oedema, both induced by carrageenan.
Suppression of PGE(2) formation by BAs via interference with mPGES1 contribute to the anti-inflammatory effectiveness of BAs and of frankincense, and may constitute a biochemical basis for their anti-inflammatory properties.
AuthorsU Siemoneit, A Koeberle, A Rossi, F Dehm, M Verhoff, S Reckel, T J Maier, J Jauch, H Northoff, F Bernhard, V Doetsch, L Sautebin, O Werz
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 162 Issue 1 Pg. 147-62 (Jan 2011) ISSN: 1476-5381 [Electronic] England
PMID20840544 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.
Chemical References
  • Anti-Inflammatory Agents
  • Triterpenes
  • boswellic acid
  • Intramolecular Oxidoreductases
  • prostaglandin-E synthase
  • Animals
  • Anti-Inflammatory Agents (pharmacology)
  • Boswellia (chemistry)
  • Catalysis
  • Cell Line
  • Cell-Free System
  • Humans
  • Immunoenzyme Techniques
  • Intramolecular Oxidoreductases (antagonists & inhibitors, metabolism)
  • Male
  • Mice
  • Rats
  • Rats, Wistar
  • Surface Plasmon Resonance
  • Triterpenes (isolation & purification, pharmacology)

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