Total flavonoids of Flos Chrysanthemi protect arterial endothelial cells against oxidative stress

作者 He, Dongxu; Ru, Xiaochen; Wen, Lei; Wen, Yuechun; Jiang, Huidi; Bruce, Iain C.; Jin, Jian; Ma, Xin; Xia, Qiang

期刊 JOURNAL OF ETHNOPHARMACOLOGY , JAN 6 2012,1:139

DOI 10.1016/j.jep.2011.10.043 PubMed 22108681

摘要 Ethnopharmacological relevance: Total flavonoids of Flos Chrysanthemi (TFFC) are known to modulate vascular functions, but their effect on endothelial cells injured by oxidative stress is unknown. Our objective was to investigate the vasoprotective effect and mechanism of action of TFFC on rat mesenteric artery exposed to superoxide anions produced by pyrogallol.Materials and methods: The vasoprotective effect and mechanism of action of TFFC on primary cultured rat mesenteric arterial endothelial cells and small mesenteric arteries was investigated using small-vessel myography, fluorescent Ca2+ measurement, fluorescent membrane potential measurement and oxidative fluorescent studies.Results: Experiments using small-vessel myography of third-order rat mesenteric arterial rings showed that pretreatment with pyrogallol (10-1000 mu M), an auto-oxidizing source of superoxide anions, dose-dependently decreased ACh-induced endothelium-dependent relaxation. TFFC (2.5-320 mg/L) evoked a concentration-dependent dilation (pD(2): 29.6 +/- 0.276 mg/L), which was weakened by ChTX plus apamin. TFFC markedly attenuated the inhibition of vasorelaxation induced by pyrogallol (E-max elevated from 50.4 +/- 7.36% to 86.2 +/- 3.61%, and pD(2) increased from 6.74 +/- 0.06 to 7.28 +/- 0.12). Furthermore, in primary cultured endothelial cells, fluorescent Ca2+ measurement, fluorescent membrane potential measurement and oxidative fluorescent studies demonstrated that ACh-induced endothelial Ca2+ influx and hyperpolarization were significantly weakened by the increased basal superoxide level induced by pyrogallol. When the endothelial cells were concurrently exposed to TFFC, the impairment effect of oxidative stress on ACh-induced Ca2+ influx, hyperpolarization and vasorelaxation were attenuated due to its superoxide-lowering activity.Conclusion: This study shows that oxidative stress has a pronounced deleterious effect on EDHF-mediated vasorelaxation to ACh in rat mesenteric artery. TFFC has vasodilating effect and protects EDHF-mediated vasodilator reactivity from oxidative stress. Thus, our experiments suggest that TFFC is potentially useful for the development of therapeutic treatments for cardiovascular diseases associated with oxidative stress. (C) 2011 Elsevier Ireland Ltd. All rights reserved.