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.

Inhibition of microsomal prostaglandin E(2) synthase-1 as a molecular basis for the anti-inflammatory actions of boswellic acids from frankincense / Siemoneit, U; Koeberle, A; Rossi, Antonietta; Dehm, F; Verhoff, M; Reckel, S; Maier, T; Jauch, J; Northoff, H; Bernhard, F; Doetsch, V; Sautebin, Lidia; Werz, O.. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - 162:1(2011), pp. 147-162. [10.1111/j.1476-5381.2010.01020.x]

Inhibition of microsomal prostaglandin E(2) synthase-1 as a molecular basis for the anti-inflammatory actions of boswellic acids from frankincense.

ROSSI, ANTONIETTA;SAUTEBIN, LIDIA;
2011

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.
2011
Inhibition of microsomal prostaglandin E(2) synthase-1 as a molecular basis for the anti-inflammatory actions of boswellic acids from frankincense / Siemoneit, U; Koeberle, A; Rossi, Antonietta; Dehm, F; Verhoff, M; Reckel, S; Maier, T; Jauch, J; Northoff, H; Bernhard, F; Doetsch, V; Sautebin, Lidia; Werz, O.. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - 162:1(2011), pp. 147-162. [10.1111/j.1476-5381.2010.01020.x]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/381408
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