title: Xyloketal B attenuates atherosclerotic plaque formation and endothelial dysfunction in apolipoprotein e deficient mice.
abstract: 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.
authors: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. yuwuwei@live.com.
authors: Li-Yan
authors: LY
authors: Zhao
authors: Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510080, China. mdlijie@sina.com.
authors: Jie
authors: J
authors: Li
authors: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. yuanfeng@mail2.sysu.edu.cn.
authors: Feng
authors: F
authors: Yuan
authors: VIP Healthcare Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China. limeimed@163.com.
authors: Mei
authors: M
authors: Li
authors: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. 543450713@qq.com.
authors: Quan
authors: Q
authors: Zhang
authors: Yun-Ying
authors: YY
authors: Huang
authors: Department of Applied Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510080, China. cespjy@mail.sysu.edu.cn.|Department of Education of Guangdong Province, Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism, Sun Yat-sen University, Guangzhou 510080, China. cespjy@mail.sysu.edu.cn.
authors: Ji-Yan
authors: JY
authors: Pang
authors: Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangzhou 510080, China. drbinzhang@163.com.
authors: Bin
authors: B
authors: Zhang
authors: Lab for Basic Research of Life Science, School of Medicine, Tibet Institute for Nationalities, Xianyang 712082, China. xzmysfy@163.com.
authors: Fang-Yun
authors: FY
authors: Sun
authors: Departments of Surgery and Physiology, Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1G6, Canada. hss.sun@utoronto.ca.
authors: Hong-Shuo
authors: HS
authors: Sun
authors: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. 2558418023@qq.com.
authors: Qian
authors: Q
authors: Li
authors: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. caolu11192@126.com.
authors: Lu
authors: L
authors: Cao
authors: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. 290496167@qq.com.
authors: Yu
authors: Y
authors: Xie
authors: Department of Applied Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510080, China. ceslyc@mail.sysu.edu.cn.|Department of Education of Guangdong Province, Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism, Sun Yat-sen University, Guangzhou 510080, China. ceslyc@mail.sysu.edu.cn.
authors: Yong-Cheng
authors: YC
authors: Lin
authors: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. liujie@mail.sysu.edu.cn.
authors: Jie
authors: J
authors: Liu
authors: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. tanhm@mail.sysu.edu.cn.|Department of Education of Guangdong Province, Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism, Sun Yat-sen University, Guangzhou 510080, China. tanhm@mail.sysu.edu.cn.
authors: Hong-Mei
authors: HM
authors: Tan
authors: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. wangglei@mail.sysu.edu.cn.|Department of Education of Guangdong Province, Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism, Sun Yat-sen University, Guangzhou 510080, China. wangglei@mail.sysu.edu.cn.
authors: Guan-Lei
authors: GL
authors: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D058226:Plaque, Atherosclerotic / Q000209:etiology / Q000517:prevention & control*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011714:Pyrans / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D002317:Cardiovascular Agents; D011714:Pyrans; C515343:xyloketal B; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt