Abstract | BACKGROUND AND PURPOSE:
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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSIONS AND IMPLICATIONS: 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.
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Authors | U 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 |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 162
Issue 1
Pg. 147-62
(Jan 2011)
ISSN: 1476-5381 [Electronic] England |
PMID | 20840544
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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 Synthases
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Topics |
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- Boswellia
(chemistry)
- Catalysis
- Cell Line
- Cell-Free System
- Humans
- Immunoenzyme Techniques
- Intramolecular Oxidoreductases
(antagonists & inhibitors, metabolism)
- Male
- Mice
- Prostaglandin-E Synthases
- Rats
- Rats, Wistar
- Surface Plasmon Resonance
- Triterpenes
(isolation & purification, pharmacology)
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