title: Traditional Chinese medicine xin-mai-jia recouples endothelial nitric oxide synthase to prevent atherosclerosis in vivo.
abstract: Endothelial dysfunction, which is caused by endothelial nitric oxide synthase (eNOS) uncoupling, is an initial step in atherosclerosis. This study was designed to explore whether Chinese medicine xin-mai-jia (XMJ) recouples eNOS to exert anti-atherosclerotic effects. Pretreatment of XMJ (25, 50, 100 μg/ml) for 30 minutes concentration-dependently activated eNOS, improved cell viabilities, increased NO generations, and reduced ROS productions in human umbilical vein endothelial cells incubated with H2O2for 2 hours, accompanied with restoration of BH4. Importantly, these protective effects produced by XMJ were abolished by eNOS inhibitor L-NAME or specific eNOS siRNA in H2O2-treated cells. In ex vivo experiments, exposure of isolated aortic rings from rats to H2O2for 6 hours dramatically impaired acetylcholine-induced vasorelaxation, reduced NO levels and increased ROS productions, which were ablated by XMJ in concentration-dependent manner. In vivo analysis indicated that administration of XMJ (0.6, 2.0, 6.0 g/kg/d) for 12 weeks remarkably recoupled eNOS and reduced the size of carotid atherosclerotic plaque in rats feeding with high fat diet plus balloon injury. In conclusion, XMJ recouples eNOS to prevent the growth of atherosclerosis in rats. Clinically, XMJ is potentially considered as a medicine to treat patients with atherosclerosis.
authors.affiliation: College of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Yin
authors.affiliation: College of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
authors.forename: Mo-Li
authors.initials: ML
authors.lastname: Zhu
authors.affiliation: Department of Drug and Cosmetics Supervision, Henan Food and Drug Administration, Zhengzhou, 450018, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wan
authors.affiliation: College of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
authors.forename: Guo-Pin
authors.initials: GP
authors.lastname: Pan
authors.affiliation: College of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
authors.forename: Jun-Xiu
authors.initials: JX
authors.lastname: Lu
authors.affiliation: College of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
authors.forename: Song
authors.initials: S
authors.lastname: Ping
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Sanquan College of Xinxiang Medical University, Xinxiang, 453003, China.
authors.forename: Fan-Rong
authors.initials: FR
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The People's Hospital of Xishui County, Huangang, Hubei, China.
authors.forename: Hai-Ya
authors.initials: HY
authors.lastname: Yu
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.affiliation: College of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Jian
authors.affiliation: Sanquan College of Xinxiang Medical University, Xinxiang, 453003, China.|Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Liu
authors.affiliation: Biology and Chemistry, Denison University, Granville, OH, USA.
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Zhang
authors.affiliation: College of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
authors.forename: Guang-Rui
authors.initials: GR
authors.lastname: Wan
authors.affiliation: College of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.|The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors.forename: Shuang-Xi
authors.initials: SX
authors.lastname: Wang
authors.affiliation: College of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D008516:Medicine, Chinese Traditional; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III