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• W1672254856 startingPage "952" @default.
• W1672254856 abstract "Background and purpose: The selective inhibition of prostaglandin (PG)E 2 formation via interference with microsomal PGE 2 synthase (mPGES)‐1 could have advantages in the treatment of PGE 2 ‐associated diseases, such as inflammation, fever and pain, compared with a general suppression of all PG biosynthesis, provided by inhibition of cyclooxygenase (COX)‐1 and 2. Here, we addressed whether the naturally occurring acylphloroglucinol myrtucommulone (MC) from Myrtus communis L. (myrtle) affected mPGES‐1. Experimental approach: The effect of MC on PGE 2 formation was investigated in a cell‐free assay by using microsomal preparations of interleukin‐1β‐stimulated A549 cells as the source of mPGES‐1, in intact A549 cells, and in lipopolysaccharide‐stimulated human whole blood. Inhibition of COX‐1 and COX‐2 activity in cellular and cell‐free assays was assessed by measuring 12(S)‐hydroxy‐5‐cis‐8,10‐trans‐heptadecatrienoic acid and 6‐oxo PGF 1α formation. Key results: MC concentration‐dependently inhibited cell‐free mPGES‐1‐mediated conversion of PGH 2 to PGE 2 (IC 50 = 1 µmol·L −1 ). PGE 2 formation was also diminished in intact A549 cells as well as in human whole blood at low micromolar concentrations. Neither COX‐2 activity in A549 cells nor isolated human recombinant COX‐2 was significantly affected by MC up to 30 µmol·L −1 , and only moderate inhibition of cellular or cell‐free COX‐1 was evident (IC 50 > 15 µmol·L −1 ). Conclusions and implications: MC is the first natural product to inhibit mPGES‐1 that efficiently suppresses PGE 2 formation without significant inhibition of the COX enzymes. This provides an interesting pharmacological profile suitable for interventions in inflammatory disorders, without the typical side effects of coxibs and non‐steroidal anti‐inflammatory drugs." @default.
• W1672254856 created "2016-06-24" @default.
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• W1672254856 date "2009-03-01" @default.
• W1672254856 modified "2023-10-16" @default.
• W1672254856 title "Myrtucommulone, a natural acylphloroglucinol, inhibits microsomal prostaglandin E2 synthase-1" @default.
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• W1672254856 doi "https://doi.org/10.1111/j.1476-5381.2009.00070.x" @default.
• W1672254856 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2697720" @default.
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