Naringin suppresses the mitogenic effect of lysophosphatidylcholine on vascular smooth muscle cells

Naringin, a flavonoid found in citrus species and grapes, has anti-inflammatory, anti-oxidative properties. In this study, we investigated whether naringin protects vascular smooth muscle cells (VSMCs) from the mitogenic effect of lysophosphatidylcholine. Lysophosphatidylcholine, an atherogenic lysophospholipid of oxidized low density lipoprotein (LDL), is known to impair endothelial release of nitric oxide, up-regulate the expression of adhesion molecules, and promote the proliferation of VSMCs. VSMCs were prepared from the aortas of Sprague-Dawley rats, and cultured in DMEM/F12 media. Near-confluent cells were incubated with 0, 10, or 100 muM of naringin for 24 hours, and then incubated with 0, 10, 20, or 100 muM of lysophosphatidylcholine. Lysophosphatidylcholine promoted the growth of VSMCs, whereas naringin suppressed its mitogenic effect on VSMCs. In an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay, lysophosphatidylcholine promoted cell proliferation by 63 +/- 24% and 89 +/- 17% at 10 muM and 20 muM respectively, when compared with the control group (p < 0.01). [H-3]-thymidine incorporation assay showed that the degree of DNA replication also increased by 61 +/- 25% and 92 +/- 25% at 10 muM and 20 muM of lysophosphatidylcholine (p < 0.01). Naringin at 100 AM significantly suppressed the mitogenic effect of lysophosphatidylcholine on VSMCs by 34 5% (MTT assay), and 35 +/- 5% ([H-3]-thymidine incorporation assay) (p = 0.01). This study demonstrates that naringin suppresses the mitogenic effect of lysophosphatidylcholine on VSMCs, whereas lysophosphatidylcholine promotes the proliferation of VSMCs. (C) 2003 Elsevier Inc. All rights reserved.