Diacerein is a potent and selective inhibitor of palmitoylethanolamide inactivation with analgesic activity in a rat model of acute inflammatory pain

Stefania Petrosino, Akbar Ahmad, Gabriele Marcolongo, Emanuela Esposito, Marco Allarà, Roberta Verde, Salvatore Cuzzocrea, Vincenzo Di Marzo

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Palmitoylethanolamide (PEA) is produced by mammalian cells from its biosynthetic precursor, N-palmitoyl-phosphatidyl-ethanolamine, and inactivated by enzymatic hydrolysis to palmitic acid and ethanolamine. Apart from fatty acid amide hydrolase (FAAH), the N-acylethanolamine-hydrolyzing acid amidase (NAAA), a lysosomal enzyme, was also shown to catalyze the hydrolysis of PEA and to limit its analgesic and anti-inflammatory action. Here we report the finding of a new potential inhibitor of NAAA, EPT4900 (4,5-diacetyloxy-9,10-dioxo-anthracene-2-carboxylic acid, diacerein). EPT4900 exhibited a high inhibitory activity on human recombinant NAAA over-expressed in HEK293 cells (HEK-NAAA cells). EPT4900 selectively increased the levels of PEA in intact HEK-NAAA cells, and inhibited inflammation as well as hyperalgesia in rats treated with an intraplantar injection of carrageenan. This latter effect was accompanied by elevation of PEA endogenous levels in the paw skin.

Original languageEnglish (US)
Pages (from-to)9-14
Number of pages6
JournalPharmacological Research
Volume91
DOIs
StatePublished - Jan 2015

Keywords

  • Diacerein
  • Inflammation
  • NAAA
  • Palmitoylethanolamide

ASJC Scopus subject areas

  • Pharmacology

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