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Isoliquiritigenin Ameliorates Indomethacin-Induced Small Intestinal Damage by Inhibiting NOD-Like Receptor Family, Pyrin Domain-Containing 3 Inflammasome Activation.
- Source :
-
Pharmacology [Pharmacology] 2018; Vol. 101 (5-6), pp. 236-245. Date of Electronic Publication: 2018 Jan 26. - Publication Year :
- 2018
-
Abstract
- Activation of the NOD-Like Receptor Family, Pyrin Domain-Containing 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1, triggers pro-caspase-1 cleavage promoting the processing of pro-interleukin (IL)-1β into mature IL-1β, which is critical for the development of non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy. We investigated the effects of isoliquiritigenin, a flavonoid derived from the roots of Glycyrrhiza species, on NSAID-induced small intestinal damage and the inflammasome activation. To induce enteropathy, mice were administered indomethacin by gavage with or without isoliquiritigenin pretreatment. Some mice received an intraperitoneal injection of recombinant murine IL-1β in addition to isoliquiritigenin and indomethacin. Indomethacin induced small intestinal damage and increased protein levels of cleaved caspase-1 and mature IL-1β in the small intestine. Treatment with 7.5 and 75 mg/kg isoliquiritigenin inhibited indomethacin-induced small intestinal damage by 40 and 56%, respectively. Isoliquiritigenin also inhibited the indomethacin-induced increase in cleaved caspase-1 and mature IL-1β protein levels, whereas it did not affect the mRNA expression of NLRP3, ASC, caspase-1, and IL-1β. Protection against intestinal damage in isoliquiritigenin-treated mice was completely abolished with exogenous IL-1β. NLRP3-/- and caspase-1-/- mice exhibited resistance to intestinal damage, and isoliquiritigenin treatment failed to inhibit the damage in NLRP3-/- and caspase-1-/- mice. Isoliquiritigenin prevents NSAID-induced small intestinal damage by inhibiting NLRP3 inflammasome activation.<br /> (© 2018 S. Karger AG, Basel.)
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal toxicity
Caspase 1 genetics
Chalcones administration & dosage
Dose-Response Relationship, Drug
Inflammasomes metabolism
Interleukin-1beta metabolism
Intestine, Small pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
NLR Family, Pyrin Domain-Containing 3 Protein genetics
Chalcones pharmacology
Indomethacin toxicity
Inflammasomes drug effects
Intestine, Small drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0313
- Volume :
- 101
- Issue :
- 5-6
- Database :
- MEDLINE
- Journal :
- Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 29393276
- Full Text :
- https://doi.org/10.1159/000486599