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Safranal inhibits NLRP3 inflammasome activation by preventing ASC oligomerization.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2021 Jul 15; Vol. 423, pp. 115582. Date of Electronic Publication: 2021 May 18. - Publication Year :
- 2021
-
Abstract
- NLRP3 inflammasome is involved in several chronic inflammatory diseases. The inflammatory effect of the NLRP3 inflammasome is executed through IL-1β and IL-18. Therefore, IL-1β is one of the primary targets in chronic inflammatory conditions. However, current treatment regimens are dependent on anti- IL-1β biologicals. The therapies targeting IL-1β through inhibition of NLRP3 inflammasome are thus being actively explored. We identified safranal, a small molecule responsible for the essence of saffron as a potential inhibitor of the NLRP3 inflammasome. Safranal significantly suppressed the release of IL-1β from ATP stimulated J774A.1 and bone marrow-derived macrophages (BMDMs) by regulating CASP1 and CASP8 dependent cleavage of pro-IL-1β. Safranal markedly suppressed the expression of NLRP3 and its ATPase activity. Safranal treatment enhanced the expression of NRF2, whereas, si-RNA mediated silencing of Nrf2 abrogated the anti-NLRP3 effect of safranal. Furthermore, safranal inhibited ASC oligomerization and formation of ASC specks. Safranal also displayed anti-NLRP3 activity in multiple mice models. Treatment of animals with safranal reduced the production of IL-1β in ATP elicited peritoneal inflammation, MSU induced air pouch inflammation, and MSU injected foot paw edema in mice. Thus, our data projects safranal as a potential preclinical drug candidate against NLRP3 inflammasome triggered chronic inflammation.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Line
Cells, Cultured
Cyclohexenes therapeutic use
Dose-Response Relationship, Drug
Female
Humans
Inflammation chemically induced
Inflammation drug therapy
Inflammation metabolism
Mice
Mice, Inbred BALB C
Terpenes therapeutic use
CARD Signaling Adaptor Proteins antagonists & inhibitors
CARD Signaling Adaptor Proteins metabolism
Cyclohexenes pharmacology
NLR Family, Pyrin Domain-Containing 3 Protein antagonists & inhibitors
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Terpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0333
- Volume :
- 423
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 34019860
- Full Text :
- https://doi.org/10.1016/j.taap.2021.115582