Diacerein is a potent and selective inhibitor of palmitoylethanolamide inactivation with analgesic activity in a rat model of acute inflammatory pain
| Autor: | Akbar Ahmad, Marco Allarà, Vincenzo Di Marzo, Gabriele Marcolongo, Roberta Verde, Salvatore Cuzzocrea, Emanuela Esposito, Stefania Petrosino |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Diacerein Anti-Inflammatory Agents Pain Anthraquinones Palmitic Acids Carrageenan Amidase Amidohydrolases Palmitic acid Rats Sprague-Dawley chemistry.chemical_compound Fatty acid amide hydrolase medicine Animals Humans Palmitoylethanolamide Skin Pharmacology chemistry.chemical_classification Inflammation Analgesics Chemistry Diacerein NAAA Palmitoylethanolamide Inflammation NAAA Amides Disease Models Animal Enzyme HEK293 Cells Biochemistry Ethanolamines Hyperalgesia medicine.symptom medicine.drug |
| Zdroj: | Pharmacological research 91 (2015): 9–14. doi:10.1016/j.phrs.2014.10.008 info:cnr-pdr/source/autori:Petrosino, Stefania; Ahmad, Akbar; Marcolongo, Gabriele; Esposito, Emanuela; Allarà, Marco; Verde, Roberta; Cuzzocrea, Salvatore; Di Marzo, Vincenzo Di/titolo:Diacerein is a potent and selective inhibitor of palmitoylethanolamide inactivation with analgesic activity in a rat model of acute inflammatory pain/doi:10.1016%2Fj.phrs.2014.10.008/rivista:Pharmacological research (Print)/anno:2015/pagina_da:9/pagina_a:14/intervallo_pagine:9–14/volume:91 |
| DOI: | 10.1016/j.phrs.2014.10.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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