LAUSR

Artemisinin is an endoperoxide sesquiterpene lactone from Artemisia annua L with multiple beneficial effects, including anti-inflammation, anti-oxidant and vascular protection. Recent studies have found that inflammation along with autophagy deficiency in macrophages are the possible reasons for foam cell accumulation in the intima, which leads to atherosclerotic plaque formation. The primary aim of this study was to explore the inhibiting effect of artemisinin on atherosclerosis in high-fat diet (HFD)-fed ApoE mice and investigate the probable mechanism. Artemisinin (50, 100 mg/kg, intragastric administration) treatment effectively inhibited foamy macrophage transformation and decreased atherosclerotic plaque formation in atherosclerotic mice. Moreover, artemisinin promoted AMP activated protein kinase (AMPK) activation, inhibited mammalian target of rapamycin (mTOR) and uncoordinated-51-like kinases 1 (ULK1) phosphorylation, increased LC-3II accumulation and P62 degradation, and thereby enhancing macrophage autophagy. Besides, the inhibiting effect of artemisinin on mTOR and ULK1 phosphorylation could be abrogated by AMPK knockdown, suggesting AMPK was the essential target of artemisinin on promoting macrophage autophagy. Our study indicated that artemisinin alleviated atherosclerotic lesions by accelerating macrophage autophagy via AMPK/mTOR/ULK1 pathway.