PMID- 14604680 OWN - NLM STAT- MEDLINE DCOM- 20040730 LR - 20190901 IS - 0968-0896 (Print) IS - 0968-0896 (Linking) VI - 11 IP - 23 DP - 2003 Nov 17 TI - Relationship between protective effect of xanthone on endothelial cells and endogenous nitric oxide synthase inhibitors. PG - 5171-7 AB - 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. FAU - Jiang, De-Jian AU - Jiang DJ AD - Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China. FAU - Hu, Gao-Yun AU - Hu GY FAU - Jiang, Jun-Lin AU - Jiang JL FAU - Xiang, Hong-Lin AU - Xiang HL FAU - Deng, Han-Wu AU - Deng HW FAU - Li, Yuan-Jian AU - Li YJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Bioorg Med Chem JT - Bioorganic & medicinal chemistry JID - 9413298 RN - 0 (Chemokine CCL2) RN - 0 (Enzyme Inhibitors) RN - 0 (Nitrates) RN - 0 (Nitrites) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Xanthones) RN - 0 (dimethylarginine) RN - 94ZLA3W45F (Arginine) RN - 9749WEV0CA (xanthone) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 3.5.- (Amidohydrolases) RN - EC 3.5.3.18 (dimethylargininase) SB - IM MH - Amidohydrolases/metabolism MH - Arginine/analogs & derivatives/metabolism MH - Cell Adhesion MH - Cells, Cultured MH - Chemokine CCL2/metabolism MH - Endothelium, Vascular/cytology/*drug effects/enzymology/metabolism MH - Enzyme Inhibitors/*pharmacology MH - L-Lactate Dehydrogenase/metabolism MH - Monocytes/cytology MH - Nitrates/metabolism MH - Nitric Oxide Synthase/*antagonists & inhibitors MH - Nitrites/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - Xanthones/*pharmacology EDAT- 2003/11/08 05:00 MHDA- 2004/07/31 05:00 CRDT- 2003/11/08 05:00 PHST- 2003/11/08 05:00 [pubmed] PHST- 2004/07/31 05:00 [medline] PHST- 2003/11/08 05:00 [entrez] AID - S0968089603005637 [pii] AID - 10.1016/j.bmc.2003.08.015 [doi] PST - ppublish SO - Bioorg Med Chem. 2003 Nov 17;11(23):5171-7. doi: 10.1016/j.bmc.2003.08.015.