Homotherapy for heteropathy: therapeutic effect of Butein in NLRP3-driven diseases.
Cell Commun Signal
; 22(1): 315, 2024 Jun 07.
Article
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| MEDLINE
| ID: mdl-38849890
ABSTRACT
BACKGROUND:
Aberrant inflammatory responses drive the initiation and progression of various diseases, and hyperactivation of NLRP3 inflammasome is a key pathogenetic mechanism. Pharmacological inhibitors of NLRP3 represent a potential therapy for treating these diseases but are not yet clinically available. The natural product butein has excellent anti-inflammatory activity, but its potential mechanisms remain to be investigated. In this study, we aimed to evaluate the ability of butein to block NLRP3 inflammasome activation and the ameliorative effects of butein on NLRP3-driven diseases.METHODS:
Lipopolysaccharide (LPS)-primed bone-marrow-derived macrophages were pretreated with butein and various inflammasome stimuli. Intracellular potassium levels, ASC oligomerization and reactive oxygen species production were also detected to evaluate the regulatory mechanisms of butein. Moreover, mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis were used to test whether butein has protective effects on these NLRP3-driven diseases.RESULTS:
Butein blocks NLRP3 inflammasome activation in mouse macrophages by inhibiting ASC oligomerization, suppressing reactive oxygen species production, and upregulating the expression of the antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2). Importantly, in vivo experiments demonstrated that butein administration has a significant protective effect on the mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis.CONCLUSION:
Our study illustrates the connotation of homotherapy for heteropathy, i.e., the application of butein to broaden therapeutic approaches and treat multiple inflammatory diseases driven by NLRP3.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Lipopolisacáridos
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Especies Reactivas de Oxígeno
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Chalconas
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Inflamasomas
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Proteína con Dominio Pirina 3 de la Familia NLR
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Macrófagos
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Ratones Endogámicos C57BL
Idioma:
En
Revista:
Cell Commun Signal
Año:
2024
Tipo del documento:
Article