ReferenceID 6192
Scoparone suppresses mitophagy-mediated NLRP3 inflammasome activation in inflammatory diseases
Acta Pharmacol Sin
Recent evidence shows that targeting NLRP3 inflammasome activation is an important means to treat inflammasome-driven diseases. Scoparone, a natural compound isolated from the Chinese herb Artemisia capillaris Thunb, has
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Record Fields
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- Reference Id
- 6192
- Evidence Id
- 22782
- Core Evidence Id
- 22782
- Source Reference Id
- 5658
- Herb2 Reference Id
- HBREF006455
- Subject Paper Key
- HBIN043437_36522512
- Pubmed Id
- 36522512
- Doi
- 10.1038/s41401-022-01028-9
- Paper Title
- Scoparone suppresses mitophagy-mediated NLRP3 inflammasome activation in inflammatory diseases
- Paper Abstract
- Recent evidence shows that targeting NLRP3 inflammasome activation is an important means to treat inflammasome-driven diseases. Scoparone, a natural compound isolated from the Chinese herb Artemisia capillaris Thunb, has anti-inflammatory activity. In this study we investigated the effect of scoparone on NLRP3 inflammasome activation in inflammatory diseases. In LPS-primed, ATP or nigericin-stimulated mouse macrophage J774A.1 cells and bone marrow-derived macrophages (BMDMs), pretreatment with scoparone (50 μM) markedly restrained canonical and noncanonical NLRP3 inflammasome activation, evidenced by suppressed caspase-1 cleavage, GSDMD-mediated pyroptosis, mature IL-1β secretion and the formation of ASC specks. We then conducted a transcriptome analysis in scoparone-pretreated BMDMs, and found that the differentially expressed genes were significantly enriched in mitochondrial reactive oxygen species (ROS) metabolic process, mitochondrial translation and assembly process, as well as in inflammatory response. We demonstrated in J774A.1 cells and BMDMs that scoparone promoted mitophagy, a well-characterized mechanism to control mitochondrial quality and reduce ROS production and subsequent NLRP3 inflammasome activation. Mitophagy blockade by 3-methyladenine (3-MA, 5 mM) reversed the protective effects of scoparone on mitochondrial damage and inflammation in the murine macrophages. Moreover, administration of scoparone (50 mg/kg) exerted significant preventive effects via inhibition of NLRP3 activation in mouse models of bacterial enteritis and septic shock. Collectively, scoparone displays potent anti-inflammatory effects via blocking NLRP3 inflammasome activation through enhancing mitophagy, highlighting a potential action mechanism in treating inflammasome-related diseases for further clinical investigation.
- Journal
- Acta Pharmacol Sin
- Publish Year
- 2022
- Experiment Subject
- mouse; j774a.1 cells; nigericin-stimulated mouse macrophage j774a.1 cells; scoparone-pretreated bmdms
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Inflammasome-driven Diseases; Inflammatory Diseases; Septic Shock; Inflammasome-related Diseases; Bacterial Enteritis
- Paper Title Cn
- Paper Title En
- Scoparone suppresses mitophagy-mediated NLRP3 inflammasome activation in inflammatory diseases
- Bilingual Status
- semi_complete