Protective effects of kaempferol against endothelial damage by an improvement in nitric oxide production and a decrease in asymmetric dimethylarginine level.

作者: Hong-Bo Xiao , Jun-Fang , Xiang-Yang Lu , Xiao-jun Chen , Chao-Tan

DOI: 10.1016/J.EJPHAR.2009.06.022

关键词: Asymmetric dimethylarginineNitric oxide synthaseNitric oxideEndocrinologyHuman umbilical vein endothelial cellEndothelial dysfunctionInternal medicineChemistryBiochemistryKaempferolEndothelial NOSEndothelium

摘要: Previous investigations have shown that asymmetric dimethylarginine (ADMA) inhibits nitric oxide (NO) synthases (NOS) and ADMA is a risk factor for endothelial dysfunction. The objective of this study was to investigate the protective effect kaempferol, naturally occurring flavonoid antioxidant agent, against damage mechanisms involved. experiments were performed in aorta plasma from C57BL/6J control apolipoprotein E-deficient (ApoE(-/-)) mice treated or not with kaempferol (50 100mg/kg, intragastrically) 4 weeks, human umbilical vein cells (HUVECs) pretreated (1, 3 10 microM) 1h exposed lysophosphatidylcholine (LPC) (10 microg/mL) 24h. Kaempferol treatment improved endothelium-dependent vasorelaxation, increased maximal relaxation value, decreased half-maximum effective concentration concomitantly an increase concentration, decrease malondialdehyde (MDA) concentrations, expression aortic NOS (eNOS) as well dimethylaminohydrolase II (DDAH II) ApoE(-/-) mice. In addition, LPC caused reduction NO production, eNOS DDAH HUVECs, abolished by kaempferol. Treatment also significantly reactive oxygen species production HUVECs. present results suggest may be associated improvement level.

参考文章(52)
K. M. Mohazzab, P. M. Kaminski, M. S. Wolin, NADH oxidoreductase is a major source of superoxide anion in bovine coronary artery endothelium American Journal of Physiology-heart and Circulatory Physiology. ,vol. 266, ,(1994) , 10.1152/AJPHEART.1994.266.6.H2568
Jun-Lin Jiang, Sheng Deng, Han-Wu Deng, Pan-Yue Deng, Feng Ye, Yuan-Jian Li, Jing Yu, Tian-Lun Yang, Aspirin protected against endothelial damage induced by LDL: role of endogenous NO synthase inhibitors in rats. Acta Pharmacologica Sinica. ,vol. 25, pp. 1633- 1639 ,(2004)
Judith Murray-Rust, James Leiper, Mark McAlister, John Phelan, Sarah Tilley, Jo Santa Maria, Patrick Vallance, Neil McDonald, Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase. Nature Structural & Molecular Biology. ,vol. 8, pp. 679- 683 ,(2001) , 10.1038/90387
Akira Ito, Philip S. Tsao, Shanthi Adimoolam, Masumi Kimoto, Tadashi Ogawa, John P. Cooke, Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation. ,vol. 99, pp. 3092- 3095 ,(1999) , 10.1161/01.CIR.99.24.3092
Rainer H Böger, Stefanie M Bode-Böger, Philip S Tsao, Patrick S Lin, Jason R Chan, John P Cooke, An endogenous inhibitor of nitric oxide synthase regulates endothelial adhesiveness for monocytes. Journal of the American College of Cardiology. ,vol. 36, pp. 2287- 2295 ,(2000) , 10.1016/S0735-1097(00)01013-5
Jun-Lin Jiang, Nian-sheng Li, Yuan-Jian Li, Han-Wu Deng, Probucol preserves endothelial function by reduction of the endogenous nitric oxide synthase inhibitor level British Journal of Pharmacology. ,vol. 135, pp. 1175- 1182 ,(2002) , 10.1038/SJ.BJP.0704563
Thomas Thum, Dimitrios Tsikas, Sylvia Stein, Maximilian Schultheiss, Martin Eigenthaler, Stefan D. Anker, Philip A. Poole-Wilson, Georg Ertl, Johann Bauersachs, Suppression of endothelial progenitor cells in human coronary artery disease by the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Journal of the American College of Cardiology. ,vol. 46, pp. 1693- 1701 ,(2005) , 10.1016/J.JACC.2005.04.066
Shen Xiao, Laszlo Wagner, Rebecca J. Schmidt, Chris Baylis, Circulating endothelial nitric oxide synthase inhibitory factor in some patients with chronic renal disease Kidney International. ,vol. 59, pp. 1466- 1472 ,(2001) , 10.1046/J.1523-1755.2001.0590041466.X
Ken-ichi Setsukinai, Yasuteru Urano, Katsuko Kakinuma, Hideyuki J. Majima, Tetsuo Nagano, Development of Novel Fluorescence Probes That Can Reliably Detect Reactive Oxygen Species and Distinguish Specific Species Journal of Biological Chemistry. ,vol. 278, pp. 3170- 3175 ,(2003) , 10.1074/JBC.M209264200
Michiaki Usui, Hidehiro Matsuoka, Hiroshi Miyazaki, Seiji Ueda, Seiya Okuda, Tsutomu Imaizumi, Increased endogenous nitric oxide synthase inhibitor in patients with congestive heart failure. Life Sciences. ,vol. 62, pp. 2425- 2430 ,(1998) , 10.1016/S0024-3205(98)00225-2