Related to the content of valerenic acid
Related to the content of valerenic acid
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DOI：
10.1055/s-2007-993761
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发表时间：
2008-01-01
期刊：
影响因子：
2.7
通讯作者：
Kopp, Brigitte
中科院分区：
文献类型：
--
作者：
Trauner, Gabriele;Khom, Sophia;Kopp, Brigitte
缬草是传统上使用的一种陡峭的药物，然而，其作用机制和负责其镇静和促进睡眠的物质尚不完全清楚。由于我们以前发现戊酸是GA-BA(A)受体的亚基特异性变构调节剂，现在我们研究了不同极性的Valerian提取物对GABA(A)受体的调节与倍半萜酸(戊酸、乙酰氧基戊酸)含量的关系。用高效液相色谱法对提取物中倍半萜酸的含量进行分析。非洲爪哇卵母细胞表达由α、02和γ(2S)亚基组成的GABAA受体，并用双微电极电压钳技术研究了Valerian提取物对GABAA受体(I-GABA)氯电流的调节作用。非极性提取物对I-GABA有明显的促进作用，而极性提取物对此无明显影响。这些结果通过对一种高活性乙酸乙酯提取物的分离得到证实：同样，含有高含量戊酸的组分具有很强的受体活性。此外，乙酸乙酯提取物中倍半萜酸的去除会导致i-GABA增强作用的丧失。综上所述，我们的数据表明，缬草提取物对GABAA受体的调节程度与戊酸的含量有关。
Valeriana officinalis L. is a traditionally used steep remedy, however, the mechanism of action and the substances responsible for its sedative and sleep-enhancing properties are not fully understood. As we previously identified valerenic acid as a subunit-specific allosteric modulator of GA-BA(A) receptors, we now investigated the relation between modulation of GABA(A) receptors by Valerian extracts of different polarity and the content of sesquiterpenic acids (valerenic acid, acetoxyvalerenic acid). All extracts were analysed by HPLC concerning the content of sesquiterpenic acids. GABAA receptors composed of a,, 02 and gamma(2S) subunits were expressed in Xenopus laevis oocytes and the modulation of chloride currents through GABAA receptors (I-GABA) by Valerian extracts was investigated using the two-microelectrode voltage clamp technique. Apolar extracts induced a significant enhancement of I-GABA, whereas polar extracts showed no effect. These results were confirmed by fractionating a highly active ethyl acetate extract: again fractions with high contents of valerenic acid exhibited strong receptor activation. In addition, removal of sesquiterpenic acids from the ethyl acetate extract led to a loss Of I-GABA enhancement. In conclusion, our data show that the extent of GABAA receptor modulation by Valerian extracts is related to the content of valerenic acid.