ReferenceID 6141
Rhein regulates redox-mediated activation of NLRP3 inflammasomes in intestinal inflammation through macrophage-activated crosstalk
Br J Pharmacol
BACKGROUND AND PURPOSE: Macrophage infiltration and activation is a critical step during acute colitis. Redox-mediated Nlrp3 inflammasome activation in macrophages plays a critical role in mediating colonic inflammatory
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- Reference Id
- 6141
- Evidence Id
- 22731
- Core Evidence Id
- 22731
- Source Reference Id
- 5542
- Herb2 Reference Id
- HBREF006339
- Subject Paper Key
- HBIN042199_34882785
- Pubmed Id
- 34882785
- Doi
- 10.1111/bph.15773
- Paper Title
- Rhein regulates redox-mediated activation of NLRP3 inflammasomes in intestinal inflammation through macrophage-activated crosstalk
- Paper Abstract
- BACKGROUND AND PURPOSE: Macrophage infiltration and activation is a critical step during acute colitis. Redox-mediated Nlrp3 inflammasome activation in macrophages plays a critical role in mediating colonic inflammatory responses. Rhein isolated from the rhizome of rhubarb exhibits anti-inflammatory effects in various diseases. However, its role in regulating acute colonic inflammation is unexplored. This study was designed to investigate the protective mechanisms of rhein during acute gut inflammation and its regulation in macrophage activation. EXPERIMENTAL APPROACH: The inhibitory effect of rhein on Nlrp3 inflammasome was evaluated in activated macrophages and colitic mice. The expressions of inflammatory mediators, inflammasome complex and redox-related signaling were analyzed by ELISA kits, western blots, immunofluorescence staining and qRT-PCR. Besides, the phenotype of macrophages was also assessed by flow cytometry. Colonic inflammation was evaluated by histological analysis. KEY RESULTS: Rhein significantly decreased IL-1beta secretion via Nlrp3 inflammasome by disturbing its complex assembly in macrophages. Rhein also activated Nrf2-HO1-NQO1 pathway, inhibited Nox2 subunits expression and translocation to regulate redox balance. Moreover, rhein attenuated inflammatory responses by mediating macrophage polarization from M1 to M2 phenotype. NF-kappaB, AP-1 and MAPK signalings were also involved in improving inflammatory conditions by rhein. In mice with acute intestinal inflammation, rhein treatment attenuated clinical features, reduced macrophage infiltration into the damaged lesions to alleviate colonic inflammation. CONCLUSION AND IMPLICATIONS: Rhein regulated redox-mediated Nlrp3 inflammasome activation to protect against acute colitis, by interfering with macrophage accumulation and polarization. These findings provide a promising strategy of novel compounds for regulating mucosal inflammation in gastrointestinal disorders.
- Journal
- Br J Pharmacol
- Publish Year
- 2021
- Experiment Subject
- mouse
- Experiment Type
- Cell Experiment
- Phenotype Related
- Mucosal Inflammation; Acute Intestinal Inflammation; Acute Colonic Inflammation; Gastrointestinal Disorders; Colonic Inflammation; Acute Colitis
- Paper Title Cn
- Paper Title En
- Rhein regulates redox-mediated activation of NLRP3 inflammasomes in intestinal inflammation through macrophage-activated crosstalk
- Bilingual Status
- semi_complete