Inhibition of vascular smooth muscle cell proliferation by Gentiana lutea root extracts.
Inhibition of vascular smooth muscle cell proliferation by Gentiana lutea root extracts.
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DOI：
10.1371/journal.pone.0061393
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dixit M
中科院分区：
文献类型：
--
作者：
Kesavan R;Potunuru UR;Nastasijević B;T A;Joksić G;Dixit M
龙胆属于龙胆科开花植物家族，因其有益的胃肠和抗炎作用，在塞尔维亚传统医学中被常规使用。本研究的目的是观察龙胆苦苷、龙胆素、龙胆苦苷、去甲基龙胆苦苷、异牡丹皮苷、苦马钱素和紫穗花素等植物根部提取液对PDGF-BB刺激的大鼠主动脉平滑肌细胞增殖的抑制作用。分别采用阿拉马蓝比色法和碘化丙啶标记法进行细胞增殖和细胞周期分析。在原代培养的大鼠主动脉平滑肌细胞(RASMCs)中，PDGF-BB(20 ng/ml)可使细胞增殖增加一倍，而根提取物(1 mg/ml)可显著抑制这一作用。根提取物还可阻止PDGF诱导的同步化细胞进入S期。此外，PDGF-BB诱导的ERK1/2激活以及由此引起的细胞一氧化氮(NO)水平的升高也被该提取物阻断。这些作用是通过阻断PDGF-BB诱导的iNOS、细胞周期蛋白D1和增殖细胞核抗原的表达而实现的。对提取物成分在使用AutoDock4的上游ERK1/2激活激酶MEK1上的对接分析表明，异维他汀可能与MEK1的抑制剂结合部位结合。用纯化的异维黄素进行的实验表明，在细胞培养中，它成功地阻断了PDGF诱导的ERK1/2激活和RASMCs的增殖。因此，黄龙胆可以为动脉粥样硬化的防治提供新的候选药物。
Gentiana lutea belonging to the Gentianaceae family of flowering plants are routinely used in traditional Serbian medicine for their beneficial gastro-intestinal and anti-inflammatory properties. The aim of the study was to determine whether aqueous root extracts of Gentiana lutea consisting of gentiopicroside, gentisin, bellidifolin-8-O-glucoside, demethylbellidifolin-8-O-glucoside, isovitexin, swertiamarin and amarogentin prevents proliferation of aortic smooth muscle cells in response to PDGF-BB. Cell proliferation and cell cycle analysis were performed based on alamar blue assay and propidium iodide labeling respectively. In primary cultures of rat aortic smooth muscle cells (RASMCs), PDGF-BB (20 ng/ml) induced a two-fold increase in cell proliferation which was significantly blocked by the root extract (1 mg/ml). The root extract also prevented the S-phase entry of synchronized cells in response to PDGF. Furthermore, PDGF-BB induced ERK1/2 activation and consequent increase in cellular nitric oxide (NO) levels were also blocked by the extract. These effects of extract were due to blockade of PDGF-BB induced expression of iNOS, cyclin D1 and proliferating cell nuclear antigen (PCNA). Docking analysis of the extract components on MEK1, the upstream ERK1/2 activating kinase using AutoDock4, indicated a likely binding of isovitexin to the inhibitor binding site of MEK1. Experiments performed with purified isovitexin demonstrated that it successfully blocks PDGF-induced ERK1/2 activation and proliferation of RASMCs in cell culture. Thus, Gentiana lutea can provide novel candidates for prevention and treatment of atherosclerosis.
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影响因子：
64.8
作者：
Dimmeler, S;Fleming, I;Zeiher, AM
通讯作者：
Zeiher, AM
影响因子：
2.9
作者：
Fischmann, Thierry O.;Smith, Catherine K.;Madison, Vincent S.
通讯作者：
Madison, Vincent S.
影响因子：
5.3
作者：
Di Pietro, Natalia;Di Tomo, Pamela;Pandolfi, Assunta
通讯作者：
Pandolfi, Assunta
影响因子：
4.3
作者：
Chen, Siyu;Ding, Yan;Liu, Chang
通讯作者：
Liu, Chang
DOI：
10.1083/jcb.200804038
发表时间：
2009-05-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dumesic PA;Scholl FA;Barragan DI;Khavari PA
通讯作者：
Khavari PA