Baicalein attenuates intimal hyperplasia after rat carotid balloon injury through arresting cell-cycle progression and inhibiting ERK, Akt, and NF-κB activity in vascular smooth-muscle cells
Baicalein attenuates intimal hyperplasia after rat carotid balloon injury through arresting cell-cycle progression and inhibiting ERK, Akt, and NF-κB activity in vascular smooth-muscle cells
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DOI：
10.1007/s00210-008-0328-1
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发表时间：
2008-12-01
影响因子：
3.6
通讯作者：
Teng, Che-Ming
中科院分区：
文献类型：
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作者：
Peng, Chieh-Yu;Pan, Shiow-Lin;Teng, Che-Ming
黄芩素（5，6，7-三氧黄酮-7-O-β-D-葡萄糖醛酸苷）来源于中草药黄芩，是众所周知的脂氧合酶抑制剂。我们研究了黄芩甙介导的抑制血管平滑肌细胞（VSMC）增殖和内膜增生的球囊血管成形术在大鼠。在血管损伤研究中，黄芩素显著抑制球囊血管成形术的内膜增生。黄芩素通过[3 H]胸苷掺入、3-（4，5-二甲基噻唑-2-基）2，5-二苯基四唑溴化物（MTT）和流式细胞术测定通过脂氧合酶非依赖性途径显著抑制细胞增殖。黄芩素能显著抑制细胞周期蛋白cyclin D1、p42/44丝裂原活化蛋白激酶（MAPK）和Akt磷酸化，而对其他细胞周期调控蛋白无明显影响。此外，黄芩素减弱血清诱导的核因子-κ B（NF-κ B）的脱氧核糖核酸（DNA）结合活性。这些结果表明黄芩素通过阻断细胞周期进程和增殖事件（包括p42/44 MAPK和Akt活化以及NF-κ B活化）来阻断细胞增殖。它还抑制大鼠球囊血管损伤后内膜增生，表明治疗动脉损伤后再狭窄的治疗潜力。
Baicalein (5,6,7-trioxyflavone-7-O-beta-D-glucuronide) derived from the Chinese herb Scutellaria baicalensis is well known as a lipoxygenase inhibitor. We investigated baicalein-mediated inhibitory effects on vascular smooth-muscle cell (VSMC) proliferation and intimal hyperplasia by balloon angioplasty in the rat. In vascular injury studies, baicalein significantly suppressed intimal hyperplasia by balloon angioplasty. Baicalein significantly inhibited cell proliferation via a lipoxygenase-independent pathway using [3H]thymidine incorporation, 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT), and flow cytometry assays. At the concentrations used, no cytotoxic effect on cell culture was found. Baicalein blocks cell-cycle progression in S/G2/M phase, consistent with the cell-cycle effects, baicalein significant inhibited cyclin D1, p42/44 mitogen-activated protein kinase (MAPK), and Akt phosphorylation without change in the other cell-cycle regulatory proteins. Furthermore, baicalein attenuated serum-induced deoxyribonucleic acid (DNA) binding activity of nuclear factor kappa B (NF-kappa B). These results show that baicalein blocks cell proliferation via blocking cell-cycle progression and proliferating events, including p42/44 MAPK and Akt activations as well as NF-kappa B activation. It also inhibits intimal hyperplasia after balloon vascular injury in the rat, indicating the therapeutic potential for treating restenosis after arterial injury.