What is the effective component in suanzaoren decoction for curing insomnia? Discovery by virtual screening and molecular dynamic simulation
What is the effective component in suanzaoren decoction for curing insomnia? Discovery by virtual screening and molecular dynamic simulation
复制标题
DOI：
10.1080/07391102.2008.10507223
复制
发表时间：
2008-08-01
影响因子：
4.4
通讯作者：
Tsai, Huei-Yann
中科院分区：
文献类型：
--
作者：
Chen, Calvin Yu-Chian;Chen, Yuh-Fung;Tsai, Huei-Yann
根据几个标准建立了GABA-A受体的可靠结构。根据唑吡坦和GABA结合构象，确定结合的关键残基与我们的模拟是一致的。研究酸枣仁调节GABA-A的主要有效成分是本研究的目的。酸枣仁皂苷A是酸枣仁中的有效成分，由于体积大，不能穿透血脑屏障，不能与两个结合部位结合。另外，酸枣仁皂苷A上的糖苷基团容易被水解。相反，从酸枣仁皂苷A中提取的酸枣仁皂苷元具有最相容的结合构象。此外，Jujubogenin在GABA结合部位形成了两个关键残基β(2)-Thr226和beta(2)-Tyr229。此外，它在酸枣仁成分中获得了相对最高的评分值。此外，吸附、分布、代谢、排泄和毒性(ADMET)描述符预测酸枣仁皂苷元具有良好的血脑屏障渗透性。因此，我们认为酸枣仁素是调节GABA-A受体的有效成分。
The reliable structure of gamma aminobutyric acid type A (GABA-A) receptor was built based on several criteria. According to zolpidem and GABA binding conformations, the key residues that were indicated to be the determination of binding were consistent with our simulation. Investigation of the major effective constituents from suanzaoren to modulate the GABA-A was the aim of the study. Jujuboside A, which was indicated to be the effective constituent from suanzaoren, had no blood-brain barrier (BBB) penetration and was unable to bind at both binding sites due to its large volume. In addition, the glycoside groups on jujuboside A were easily to be hydrolyzed. In contrast, jujubogenin, which was hydrolyzed from jujuboside A, had the most compatible binding conformation. In addition, jujubogenin formed two HBs with the key residue beta(2)-Thr226 and beta(2)-Tyr229 at the GABA binding site. Moreover, it gained the comparably highest scoring values among suanzaoren constituents. Furthermore, the Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) descriptor predicted that jujubogenin have good BBB penetration. Consequently, we suggested jujubogenin to be the effective suanzaoren constituent to mediate the GABA-A receptor.