期刊
JOURNAL OF DRUG TARGETING
卷 28, 期 1, 页码 70-79出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/1061186X.2019.1616296
关键词
Atherosclerosis; artemisinin; inflammation; macrophage; AMPK; NF-kappa B; NLRP3 inflammasomes signalling
资金
- Key Science and Technology Project of Liaoning Province [2017225007]
There is increasing evidence that atherosclerosis is the significant risk factor for cardiovascular diseases, which are the leading causes of morbidity and mortality worldwide. Artemisinin is a natural endoperoxides quiterpene lactone compound in Artemisia annua L with vasculoprotective effects. The primary aim of this study was to investigate whether artemisinin could be conferred an anti-atherosclerotic effect in high-fat diet (HFD)-fed ApoE(-/-) mice and explore the possible mechanism. We found that treatment with artemisinin (50 and 100 mg/kg) effectively ameliorated atherosclerotic lesions, such as foam cell formation, hyperplasia and fibrosis in the aortic intima. Atherosclerotic mice treated with artemisinin showed reduced inflammation by up-regulating adenosine 5 '-monophosphate (AMP) activated protein kinase (AMPK) activation and by down-regulating nuclear factor-kappa B (NF-kappa B) phosphorylation and nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome expression in the aortas. In addition, artemisinin was found to promote AMPK activity in macrophages and its anti-inflammatory effect was neutralised by AMPK silence using specific siRNA. In conclusion, we demonstrate that artemisinin may protect the aortas from atherosclerotic lesions by suppression of inflammatory reaction via AMPK/NF-kappa B/NLRP3 inflammasomes signalling in macrophages.
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