ReferenceID 6152
Rosmarinic acid inhibits oxLDL-induced inflammasome activation under high-glucose conditions through downregulating the p38-FOXO1-TXNIP pathway
Biochem Pharmacol
Elevated glucose levels in diabetes mellitus is associated with increased oxidized low density lipoprotein (oxLDL). High glucose (HG) and oxLDL are key inducers of oxidative stress and inflammatory processes responsible
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Record Fields
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- Reference Id
- 6152
- Evidence Id
- 22742
- Core Evidence Id
- 22742
- Source Reference Id
- 5571
- Herb2 Reference Id
- HBREF006368
- Subject Paper Key
- HBIN042438_33011160
- Pubmed Id
- 33011160
- Doi
- 10.1016/j.bcp.2020.114246
- Paper Title
- Rosmarinic acid inhibits oxLDL-induced inflammasome activation under high-glucose conditions through downregulating the p38-FOXO1-TXNIP pathway
- Paper Abstract
- Elevated glucose levels in diabetes mellitus is associated with increased oxidized low density lipoprotein (oxLDL). High glucose (HG) and oxLDL are key inducers of oxidative stress and inflammatory processes responsible for diabetic vascular disorders. Rosmarinic acid is a polyphenol with antioxidant, anti-inflammatory and insulin-sensitizing effects. However, whether rosmarinic acid protects against diabetic atherosclerosis remains unknown. In this study, we aimed to investigate the protective effect of rosmarinic acid against diabetic atherosclerosis and the related signaling pathway. oxLDL-mediated oxidative stress upregulated thioredoxin-interacting protein (TXNIP) and subsequently induced binding of TXNIP to NLRP3 to mediate NLRP3 inflammasome assembly and activation under HG conditions in ECs. Reactive oxygen species (ROS) scavengers, p38 and FOXO1 inhibitors and TXNIP siRNA inhibited TXNIP protein upregulation and NLRP3 inflammasome assembly and activation. Rosmarinic acid abrogated TXNIP protein upregulation and the interaction between TXNIP and NLRP3 to attenuate NLRP3 inflammasome assembly and activation and eventually IL-1beta secretion in ECs through downregulating ROS production, p38 phosphorylation and FOXO1 protein induction in ECs. These findings show that rosmarinic acid inhibits endothelial dysfunction which is shown in diabetic atherosclerosis through downregulating the p38-FOXO1-TXNIP pathway and inhibiting inflammasome activation.
- Journal
- Biochem Pharmacol
- Publish Year
- 2020
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Diabetes Mellitus; Diabetic Atherosclerosis; Diabetic Vascular Disorders
- Paper Title Cn
- Paper Title En
- Rosmarinic acid inhibits oxLDL-induced inflammasome activation under high-glucose conditions through downregulating the p38-FOXO1-TXNIP pathway
- Bilingual Status
- semi_complete