Xyloketal B Attenuates Atherosclerotic Plaque Formation and Endothelial Dysfunction in Apolipoprotein E Deficient Mice

Marine Drugs

Jie Li¹  Ji-Yan Pang²  Yong-Cheng Lin²  Lu Cao³  Qian Li³  Hong-Mei Tan³  Quan Zhang³  Jie Liu⁴  Guan-Lei Wang⁴  Yu Xie⁴  Li-Yan Zhao⁴  Feng Yuan⁴  Yun-Ying Huang⁵  Hong-Shuo Sun⁶  Bin Zhang⁷  Fang-Yun Sun⁸  Mei Li⁹ 

[1] Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510080, China;Department of Applied Chemistry, School of Chemistry and Chemical Engineering,Sun Yat-sen University, Guangzhou 510080, China;Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China;Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University,Guangzhou 510080, China;Department of Pharmacy, The fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China;Departments of Surgery and Physiology, Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1G6, Canada;Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangzhou 510080, China;Lab for Basic Research of Life Science, School of Medicine, Tibet Institute for Nationalities, Xianyang 712082, China;VIP Healthcare Center, The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630, China;

关键词: xyloketals;    atherosclerosis;    endothelium;    eNOS;    apoE-deficient mice;   

DOI  :  10.3390/md13042306

来源: DOAJ

【 摘 要 】

Our previous studies demonstrated that xyloketal B, a novel marine compound with a unique chemical structure, has strong antioxidant actions and can protect against endothelial injury in different cell types cultured in vitro and model organisms in vivo. The oxidative endothelial dysfunction and decrease in nitric oxide (NO) bioavailability are critical for the development of atherosclerotic lesion. We thus examined whether xyloketal B had an influence on the atherosclerotic plaque area in apolipoprotein E-deficient (apoE−/−) mice fed a high-fat diet and investigated the underlying mechanisms. We found in our present study that the administration of xyloketal B dose-dependently decreased the atherosclerotic plaque area both in the aortic sinus and throughout the aorta in apoE−/− mice fed a high-fat diet. In addition, xyloketal B markedly reduced the levels of vascular oxidative stress, as well as improving the impaired endothelium integrity and NO-dependent aortic vasorelaxation in atherosclerotic mice. Moreover, xyloketal B significantly changed the phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt without altering the expression of total eNOS and Akt in cultured human umbilical vein endothelial cells (HUVECs). Here, it increased eNOS phosphorylation at the positive regulatory site of Ser-1177, while inhibiting phosphorylation at the negative regulatory site of Thr-495. Taken together, these findings indicate that xyloketal B has dramatic anti-atherosclerotic effects in vivo, which is partly due to its antioxidant features and/or improvement of endothelial function.

【 授权许可】

Unknown