Hepatoprotective phenylpropanoids from Scrophularia buergeriana roots against CCl4-induced toxicity:: Action mechanism and structure-activity relationship
Hepatoprotective phenylpropanoids from Scrophularia buergeriana roots against CCl4-induced toxicity:: Action mechanism and structure-activity relationship
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DOI：
10.1055/s-2002-32081
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发表时间：
2002-05-01
期刊：
影响因子：
2.7
通讯作者：
Kim, YC
中科院分区：
文献类型：
--
作者：
Lee, EJ;Kim, SR;Kim, YC
白花玄参根中的苯丙醇类化合物(玄参科)保护原代培养的大鼠肝细胞免受四氯化碳(CCl4)的毒性。在这份报告中，我们证明了两个苯丙素类化合物，4-O-E-p-methoxycinnamoyl-alpha-L-rhamnopyranoside酯(1)和对甲氧基肉桂酸(3)具有显著的保护肝脏活性；另一种用于比较的苯丙烷类化合物异阿魏酸(11)也具有同样的活性。为了确定这三种苯丙烷类化合物发挥保肝作用的机制(S)，我们测定了谷胱甘肽氧化还原系统相关酶的活性，并测定了肝脏线粒体GSH的水平。CCl4可显著降低原代培养大鼠肝细胞的GSH水平，但这三种苯丙烷均可使GSH水平显著降低。这三种苯丙烷对四氯化碳损伤大鼠肝细胞中正常降低的谷胱甘肽二硫化物还原酶和谷胱甘肽-S转移酶活性有明显的保护作用。此外，在CCl4损伤的大鼠肝细胞中，脂质过氧化副产物丙二醛的增加形成被这些苯丙烷类化合物处理后减少。我们确定了这三种苯丙烷类化合物发挥保肝活性所需的基本结构部分。α，β-不饱和酯部分似乎是发挥保肝活性所必需的。
Phenylpropanoids isolated from the roots of Scrophalaria buergeriana MIQ. (Scrophulariaceae) protected primary cultures of rat hepatocytes from toxicity induced by carbon tetrachloride (CCl4). In this report, we show that two of these phenylpropanoids, 4-O-E-p-methoxycinnamoyl-alpha-L-rhamnopyranoside ester (1) and p-methoxycinnamic acid (3) have significant hepatoprotective activity; another phenylpropanoid used for comparison, isoferulic acid (11), was equally active. To determine the mechanism(s) by which these three phenylpropanoids exerted their hepatoprotective activity, we measured activities of enzymes involved in the glutathione (GSH) redox system and assayed the level of hepatic mitochondrial GSH. The GSH levels in primary cultures of rat hepatocytes were significantly reduced with CCl4 insult, but were significantly preserved by the treatment with these three phenylpropanoids. The activities of glutathione disulfide reductase and glutathione-S-transferase which normally decrease in CCl4-injured rat hepatocytes were significantly preserved by the treatment with these three phenylpropanoids. In addition, in CCl4-injured rat hepatocytes, the increased formation of malondialdehyde, a byproduct of lipid peroxidation, was reduced by the treatment with these phenylpropanoids. We determined the essential structural moiety within these three phenylpropanoids needed to exert hepatoprotective activity. The alpha,beta-unsaturated ester moiety seemed to be essential for exerting hepatoprotective activity.