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Molecules 2018, 23(5), 1101; https://doi.org/10.3390/molecules23051101

Ursolic Acid Attenuates Atherosclerosis in ApoE−/− Mice: Role of LOX-1 Mediated by ROS/NF-κB Pathway

1
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China
2
Department of Pharmacology, College of basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao 266000, China
3
Agricultural Bio-Pharmaceutical Laboratory, Qingdao Agricultural University, Qingdao 266000, China
*
Author to whom correspondence should be addressed.
Received: 28 March 2018 / Revised: 19 April 2018 / Accepted: 28 April 2018 / Published: 7 May 2018
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Abstract

Atherosclerosis, a chronic inflammatory disease, is a major contributor to cardiovascular diseases. Ursolic acid (UA) is a phytonutrient with widely biological effects including anti-oxidative, anti-inflammatory, and so on. At present, the effect of UA on atherosclerosis and the mechanism of action are still obscure. This study focused on investigating the effects of UA on atherosclerosis both in vivo and in vitro. We first selected LOX-1 as our target, which was reckoned as a new promising receptor for treating atherosclerosis. The evaluation in vitro suggested that UA significantly decreased endothelial LOX-1 expression induced by LPS both in mRNA and protein levels. Pre-treatment of UA also inhibited TLR4/MyD88 signaling activated by LPS. Moreover, UA reduced ROS production and suppressed the activation of NF-κB stimulated by LPS. Particularly, the evaluation in vivo further verified the conclusion obtained in vitro. In ApoE−/− mice fed with an atherogenic diet, both UA (100 mg/kg/day) and simvastatin significantly attenuated atherosclerotic plaque formation and shrunk necrotic core areas. The enhanced expression of LOX-1 in atherosclerotic aorta was also dramatically decreased by administration of UA. Taken together, these results suggested that UA, with anti-atherosclerotic activity through inhibition of LOX-1 mediated by ROS/NF-κB signaling pathways, may become a valuable vascular protective candidate for the treatment of atherosclerosis. View Full-Text
Keywords: atherosclerosis; ROS; HUVECs; LOX-1 atherosclerosis; ROS; HUVECs; LOX-1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Li, Q.; Zhao, W.; Zeng, X.; Hao, Z. Ursolic Acid Attenuates Atherosclerosis in ApoE−/− Mice: Role of LOX-1 Mediated by ROS/NF-κB Pathway. Molecules 2018, 23, 1101.

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