ReferenceID 2148
Natural lactucopicrin alleviates importin-α3-mediated NF-κB activation in inflammated endothelial cells and improves sepsis in mice
Biochem Pharmacol
Lactucopicrin, a bitter sesquiterpene lactone of leafy vegetables, such as chicory, curly escarole, and lettuce, possesses anti-malarial, anti-cancer and analgesic properties. However, it remains unknown whether lactucop
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Record Fields
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- Reference Id
- 2148
- Evidence Id
- 18738
- Core Evidence Id
- 18738
- Source Reference Id
- 4337
- Herb2 Reference Id
- HBREF005134
- Subject Paper Key
- HBIN032545_33684389
- Pubmed Id
- 33684389
- Doi
- 10.1016/j.bcp.2021.114501
- Paper Title
- Natural lactucopicrin alleviates importin-α3-mediated NF-κB activation in inflammated endothelial cells and improves sepsis in mice
- Paper Abstract
- Lactucopicrin, a bitter sesquiterpene lactone of leafy vegetables, such as chicory, curly escarole, and lettuce, possesses anti-malarial, anti-cancer and analgesic properties. However, it remains unknown whether lactucopicrin could inhibit vascular endothelial nuclear factor-kappaB (NF-kappaB) activation, a hallmark of vascular inflammatory diseases including sepsis. In tumor necrosis factor-alpha-stimulated human or mouse aortic endothelial cells, lactucopicrin dose-dependently inhibited NF-kappaB activation, and concomitantly repressed both vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)-mediated monocyte adhesion. The lactucopicrin effect was not due to modulation of inhibitor of NF-kappaB kinases (IKK) alpha/beta/gamma, inhibitor of NF-kappaB alpha (IkappaBalpha), and NF-kappaB/p65 DNA binding activity. Instead, lactucopicrin inhibited importin-alpha3 expression by destabilization of its mRNA, an effect mediating the lactucopicrin effect on NF-kappaB activity. More importantly, in lipopolysaccharide (LPS)-elicited septic mice, oral gavage with lactucopicrin decreased mortality by 30.5% as compared with the control treatment. This effect was associated with inhibited importin-alpha3 expression, suppressed NF-kappaB activation and VCAM-1/ICAM-1 expression, and inhibited leukocyte influx in the vascular endothelium of both lung and aorta. Collectively, our novel data suggest that dietary supplementation with lactucopicrin inhibits endothelial NF-kappaB activation by down-regulation of importin-alpha3 and thereby improves sepsis.
- Journal
- Biochem Pharmacol
- Publish Year
- 2021
- Experiment Subject
- mouse; human; tumor necrosis factor-alpha-stimulated human or mouse aortic endothelial cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Vascular Inflammatory Diseases; Sepsis; Tumor
- Paper Title Cn
- Paper Title En
- Natural lactucopicrin alleviates importin-α3-mediated NF-κB activation in inflammated endothelial cells and improves sepsis in mice
- Bilingual Status
- semi_complete