Antioxidant effect of imperatorin from Angelica dahurica in hypertension via inhibiting NADPH oxidase activation and MAPK pathway
Antioxidant effect of imperatorin from Angelica dahurica in hypertension via inhibiting NADPH oxidase activation and MAPK pathway
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白芷欧前胡素通过抑制NADPH氧化酶激活和MAPK通路对高血压的抗氧化作用
DOI：
10.1016/j.jash.2014.04.006
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发表时间：
2014-08-01
影响因子：
--
通讯作者：
He, Langchong
中科院分区：
文献类型：
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作者：
Cao, Yanjun;Zhang, Yanmin;He, Langchong
欧前胡素（IMP）是中药白芷中的一种活性呋喃香豆素，具有舒张血管的作用。在本研究中，我们研究了IMP对自发性高血压大鼠（SHR）和人胚肾293细胞的血压（BP）和抗氧化作用的影响。SHR每日灌胃IMP（6.25、12.5和25 mg/kg/d）或Tempol（18 mg/kg/d），连续12周。硫代巴比妥酸反应物质，蛋白尿水平，超氧化物歧化酶活性进行了评估与商业试剂盒。采用逆转录聚合酶链反应和Western blot法检测肾皮质组织中NADPH氧化酶亚基的含量。采用酶联免疫吸附试验测定24 h尿8-异前列腺素F2 α。IMP（6.25、12.5和25 mg/kg/d）可显著降低SHR的收缩压和舒张压。同时，我们发现IMP处理组肾皮质超氧化物歧化酶活性显著升高。IMP治疗组肾皮质和尿中硫代巴比妥酸反应物质水平、24 h尿8-Iso-PGF 2 α排泄量和尿蛋白量均低于SHR组。结果表明，IMP处理后SHR海马NADPH氧化酶亚基mRNA表达和蛋白水平均明显降低。IMP还降低SHR肾皮质蛋白激酶B、细胞外信号调节激酶1/2、p38丝裂原活化蛋白激酶（MAPK）和c-Jun N-末端激酶的磷酸化。IMP能显著抑制H2 O2诱导的人胚肾293细胞ROS的产生，并能抑制H2 O2诱导的MAPK、蛋白激酶B的活化和NADPH氧化酶的表达。(C)2014年美国高血压学会。All rights reserved.
Imperatorin (IMP) is an active furocoumarin in the traditional Chinese medicine Angelica dahurica and has been demonstrated to have vasodilatory activity. In the present study, we investigated the effect of IMP on blood pressure (BP) and antioxidant effects in spontaneously hypertensive rats (SHR) and human embryonic kidney 293 cells. SHR were administered IMP (6.25, 12.5, and 25 mg/kg/d) or tempol (18 mg/kg/d) daily by gavage for 12 weeks. Thiobarbituric acid-reactive substances, proteinuria levels, and superoxide dismutase activity were evaluated with commercial kits. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits of the renal cortical tissues were determined by reverse transcriptase polymerase chain reaction and Western blot. Twenty-four hour urinary 8-Iso-prostaglandin F2 alpha was measured by enzyme linked immunosorbent assay. Systolic BP and diastolic BP were significantly reduced by treatment with IMP (6.25, 12.5, and 25 mg/kg/d) in SHR. Meanwhile, we found that renal cortical superoxide dismutase activities were significantly increased in IMP-treated groups. Renal cortical and urinary thiobarbituric acid-reactive substances' levels, the 24-hour urinary excretion of 8-Iso-prostaglandin F2 alpha, and proteinuria in the IMP-treated group, were lower than SHR group. After that, we found the messenger RNA expressions and protein levels of NADPH oxidase subunits were markedly reduced after IMP treated in SHR. IMP also reduced the phosphorylation of protein kinase B, extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase in renal cortical in SHR. In addition, H2O2-induced ROS production in human embryonic kidney 293 cells was markedly attenuated by IMP. H2O2-induced activation of MAPK, protein kinase B, and expression of NADPH oxidase were also attenuated by pretreatment of IMP. In summary, IMP showed antihypertensive effect via prevention of renal injury not only by reducing NADPH oxidase but also by inhibiting of MAPK pathway. (C) 2014 American Society of Hypertension. All rights reserved.