title: Relationship between protective effect of xanthone on endothelial cells and endogenous nitric oxide synthase inhibitors.
abstract: 1,3,5,6-tetrahydroxyxanthone was synthesized. The relationship between protective effect of xanthone on endothelial cells and endogenous nitric oxide synthase inhibitors was investigated. Endothelial cells were treated with ox-LDL (100 microg/mL) for 48 h. Adhesion of monocytes to endothelial cells and release of lactate dehydrogenase (LDH) was determined. Levels of tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), nitric oxide (NO) and asymmetric dimethylarginine (ADMA, an endogenous inhibitor of nitric oxide synthase) in conditioned medium and activity of dimethylarginine dimethylaminohydrolase (DDAH) in endothelial cells were measured. Incubation of endothelial cells with ox-LDL (100 microg/mL) for 48 h markedly enhanced the adhesion of monocytes to endothelial cells, increased the release of LDH, the levels of TNF-alpha, MCP-1 and ADMA, and decreased the content of NO and the activity of DDAH. Xanthone (1,3,5,6-tetrahydroxyxanthone) (1, 3 or 10 micromol/L) significantly inhibited the increased adhesion of monocytes to endothelial cells and attenuated the increased levels of LDH, MCP-1 and ADMA induced by ox-LDL. Xanthone (1,3,5,6-tetrahydroxyxanthone) (3 or 10 micromol/L) significantly attenuated the increased level of TNF-alpha and decreased level of NO and activity of DDAH by ox-LDL. The present results suggest that xanthone (1,3,5,6-tetrahydroxyxanthone) preserves endothelial cells and inhibits the increased adhesion of monocytes to endothelial cells induced by ox-LDL, and that the protective effect of xanthone (1,3,5,6-tetrahydroxyxanthone) on endothelial cells is related to reduction of ADMA concentration via increase of DDAH activity.
authors: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors: De-Jian
authors: DJ
authors: Jiang
authors: Gao-Yun
authors: GY
authors: Hu
authors: Jun-Lin
authors: JL
authors: Jiang
authors: Hong-Lin
authors: HL
authors: Xiang
authors: Han-Wu
authors: HW
authors: Deng
authors: Yuan-Jian
authors: YJ
authors: Li
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; C487735:dimethylarginine; D001120:Arginine; C009689:xanthone; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; C059999:dimethylargininase