Luteolin ameliorates endothelial dysfunction induced by oxidative stress

Abstract

Abstract: AIM: To evaluate the protective effect of luteolin on endothelial dysfunction induced by tert-butyl hydro-peroxide ( t-BOOH ) .METHODS: We observed the effect of luteolin on t-BOOH-induced contractions in the aorta rings with or without endothelium, which were incubated with luteolin ( 10^-6 to 10^-4mol/L) for 30 min before determining the concentra-tion-response to t-BOOH .Cultured endothelial cell line ( ECV304) was pretreated with different concentrations of luteolin (10^-6 to 10^-4mol/L)for 30 min and hen exposed to 10^-5mol/L t-BOOH for 24 hours .Cellmorphology was observed, and cell viability was deter-mined by MTT assay .Meanwhile, RT-PCR was used to measure the expression of eNOS and COX-1 .RESULTS: Increasing concentrations of t-BOOH pro-duced concentration-dependent contractions in aorta rings isolated from rats, luteolin effectively attenuated the contraction in a concentration-dependent manner, and the relaxation response was greater in intact endo-thelium segments .In MTT and RT-PCR assays, luteo-lin effectively reduced the cytotoxicity of t-BOOH to endothelium cell and increased the expression of nitric oxide synthase ( eNOS ) mRNA, which was greatly down-regulated by t-BOOH.CONCLUSION: Luteo-lin effectively protects the endothelium from the impairment of oxidative stress, and the protection could be related to its negative modulation towards t-BOOH-in-duced contractions in the aorta .

Key words: luteolin, aorta ring, endothelial cell, t-BOOH

CLC Number:

R965.2

PAN Fang-fang, ZHOU Yong-mei, ZHANG Min, SONG Jun-na, LIU Bao-lin. Luteolin ameliorates endothelial dysfunction induced by oxidative stress[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(4): 418-424.

References

[1] Ludmer PL,Selwyn AP,Shook TL,et al.Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries[J].N Engl J Med,1986,315 (17):1046-1051.
[2] Matsumoto T,Yoshiyama S,Wakabayashi K,et al.Ef-fects of chronic insulin on endothelial dysfunction of basi-lar arteries from established streptozotocin-diabetic rats[J].Eur J Pharmacol,2004,504(12):119-127.
[3] Panza JA ,Garcia CE,Kilcoyne CM,et al.Impaired endothelium-dependent vasodilation in patients with essential hypertension.Evidence that nitric oxide abnormality is not localized to a single signal transduction pathway[J].Cir-culation,1995,91(6):1732-1738.
[4] Fenster BE,Tsao PS,Rockson SG.Endothelial dysfunc-tion:Clinical strategies for treating oxidant stress[J].Am Heart J,2003,146(2):218-226.
[5] Selvendiran K,Koga H,Ueno T,et al.Luteolin promotes degradation in signal transducer and activator of transcrip-tion 3 in human hepatoma cells :an implication for the an-titumor potential of flavonoids[J].Cancer Res,2006,66(9):4826-4834.
[6] Qiusheng Z,Yuntao Z,Rongliang Z,et al.Effects of verbascoside and luteolin on oxidative damage in brain of heroin treated mice[J].Pharmazie,2005,60(7):539-543.
[7] Li Z,Zhou Y,Zhang N,et al.Evaluation of the anti-in-flammatory activity of luteolin in experimental models[J]. Planta Med,2007,73(3):221-226.
[8] Wang L,Han C,Wan P.Experiment research on luteolin affecting coronary circulation dynamics[J].Chin Pharma-col Bull,1992,8(5):388-390.
[9] Calderone V,Chericoni S,Martinelli C,et al.Vasorelax-ing effects of flavonoids:investigation on the possible in-volvement of potassium channels[J].Naunyn Schmiede-bergs Arch Pharmacol,2004,370(4):290-298.
[10] Chan EC,Pannangpetch P,Woodman OL.Relaxation to flavones and flavonols in rat isolated thoracic aorta:mech-anism of action and structure-activity relationships[J].J Cardiovasc Pharmacol,2000,35(2):326-333.
[11] Heymes C,Habib A ,Yang D,et al.Cyclo-oxygenase-1 and-2 contribution to endothelial dysfunction in ageing[J].Br J Pharmacol,2000,131(4):804-810.
[12] Schilling WP,Elliott SJ.Ca²⁺ signaling mechanisms of vascular endothelial cells and their role in oxidant-induced endothelial cell dysfunction[J].Am J Physiol,1992,262(6):H1617-H1630.
[13] Elliott SJ,Schilling WP.Oxidant stress alters Na + pump and Na⁺-K⁺-Cl^--cotransporter activities in vascular en-dothelial cells[J].Am J Physiol,1992,263(1 Pt 2):H96-H102.
[14] Gurtner GH,Burke-Wolin T.Interactions of oxidant stress and vascular reactivity[J].Am J Phy siol,1991,260 (4Pt1)L207-L211.
[15] Garcia-Cohen EC,Marin J,Diez-Picazo LD,et al.Oxi-dative stress induced by ter t-butyl hydroperoxide causes vasoconstriction in the aorta from hypertensive and aged rats:role of cyclooxygenase-2 isoform[J].J Pharmacol Exp Ther,2000,293(1):75-81.
[16] Harrison DG,Ohara Y.Physiologic consequences of in-creased vascular oxidant stresses in hypercholesterolemia and atherosclerosis :implications for impaired vasomotion[J].Am J Cardiol,1995,75(6):75B-81B.
[17] Witting PK,Rayner BS,Wu BJ,et al.Hydrogen perox-ide promotes endothelial dysfunction by stimulating multiple sources of superoxide anion radical production and de-creasing nitric oxide bioavailability[J].Cell Physiol Bio-chem,2007,20(5):255-268.
[18] Boulden BM,Widder JD,Allen JC,et al.Early Determi-nants of H2O2-Induced Endothelial Dy sfunction[J].Free Radic Biol Med,2006,41(5):810-817.