In Vitro Effect of Valepotriates Isolated from Valeriana glechomifolia on Rat P-Type ATPases
In Vitro Effect of Valepotriates Isolated from Valeriana glechomifolia on Rat P-Type ATPases
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DOI：
10.1055/s-0030-1271084
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发表时间：
2011-10-01
期刊：
影响因子：
2.7
通讯作者：
Quintas, Luis E. M.
中科院分区：
文献类型：
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作者：
Bettero, Gustavo M.;Salles, Luisa;Quintas, Luis E. M.
缬草酸酯是缬草科植物中含量不定的环烯醚萜类化合物，可能是缬草属植物具有抗焦虑作用的生物活性化合物之一。另一方面，非特异性细胞毒性也被描述过。然而，目前还没有确定这些化合物的特定分子靶点。本实验研究了缬草中戊酸酯、乙酰丙酸酯和1- β -乙酰丙酸酯对大鼠p型atp酶活性的影响。Valepotriates在使用的最高浓度（100 μ M）下不影响大鼠骨骼肌sarco/内质网Ca2+- atp酶（SERCA）活性。相比之下，相同浓度抑制了大鼠胃上皮中大约一半的H+/K+- atp酶活性（戊酸盐54.6 +/- 3.2%，乙酰丙酸盐60.7 +/- 7.3%，1- β -乙酰丙酸盐50.2 +/- 3.1%；平均+/- SEM， n = 3-5）。最后，这些物质对Na+/K+- atp酶的抑制作用最强，对大鼠肾α - 1亚型（戊酸酯21.2，乙酰丙酸酯22.8,1- β -乙酰丙酸酯24.4）和大脑半球α - 2/ α - 3亚型（戊酸酯19.4，乙酰丙酸酯42.3,1- β -乙酰丙酸酯38.3）的抑制曲线具有相似的IC50 （μ M）。我们的研究结果表明，缬戊酸盐对p型atp酶的抑制是不同的，Na+/K+- atp酶可能是它们在体内的分子靶点之一。
Valepotriates are iridoids found in variable amounts in Valerianaceae and might be among the bioactive compounds which confer anxiolytic properties to the Valeriana species. On the other hand, unspecific cytotoxicity has also been described. Presently, however, no particular molecular target has been defined for these compounds. Here we studied the effect of valtrate, acevaltrate, and 1-beta-acevaltrate isolated from Valeriana glechomifolia on the enzymatic activity of rat P-type ATPases. Valepotriates did not affect rat skeletal muscle sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity at the highest concentration used (100 mu M). In contrast, the same concentration inhibited roughly half of the total H+/K+-ATPase activity from rat gastric epithelium (valtrate 54.6 +/- 3.2%, acevaltrate 60.7 +/- 7.3%, 1-beta-acevaltrate 50.2 +/- 3.1%; mean +/- SEM, n = 3-5). Finally, these substances showed the highest inhibitory potency toward Na+/K+-ATPase, and the inhibition curves obtained provided a similar IC50 (in mu M) for rat kidney alpha 1 isoform (valtrate 21.2, acevaltrate 22.8, 1-beta-acevaltrate 24.4) and brain hemispheres alpha 2/alpha 3 isoforms (valtrate 19.4, acevaltrate 42.3, 1-beta-acevaltrate 38.3). Our results suggest that P-type ATPases are differentially inhibited by valepotriates and that Na+/K+-ATPase might be one of their molecular targets in vivo.