• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>International Journal of Molecular Sciences >In Silico Studies on Triterpenoid Saponins Permeation through the Blood–Brain Barrier Combined with Postmortem Research on the Brain Tissues of Mice Affected by Astragaloside IV Administration
【2h】

In Silico Studies on Triterpenoid Saponins Permeation through the Blood–Brain Barrier Combined with Postmortem Research on the Brain Tissues of Mice Affected by Astragaloside IV Administration

机译：在计算机模拟中研究三萜类皂苷通过血脑屏障的渗透作用与黄芪甲苷IV给药对小鼠脑组织的死后研究相结合的研究

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

As the number of central nervous system (CNS) drug candidates is constantly growing, there is a strong need for precise a priori prediction of whether an administered compound is able to cross the blood–brain barrier (BBB). The aim of this study was to evaluate the ability to cross the BBB of triterpenoid saponins occurring in roots. The research was carried out using in silico methods combined with postmortem studies on the brain tissues of mice treated with isolated astragaloside IV (AIV). Firstly, to estimate the ability to cross the BBB by the tested saponins, new quantitative structure–activity relationship (QSAR) models were established. The reliability and predictability of the model based on the values of the blood–brain barrier penetration descriptor (logBB), the difference between the -octanol/water and cyclohexane/water logP (ΔlogP), the logarithm of n-octanol/water partition coefficient (logP ), and the excess molar refraction (E) were both confirmed using the applicability domain (AD). The critical leverage value h* was found to be 0.128. The relationships between the standardized residuals and the leverages were investigated here. The application of an in vitro acetylcholinesterase-inhibition test showed that AIV can be recognized as the strongest inhibitor among the tested compounds. Therefore, it was isolated for the postmortem studies on brain tissues and blood using semi-preparative HPLC with the mobile phase composed of water, methanol, and ethyl acetate (1.7:2.1:16.2 / / ). The results of the postmortem studies on the brain tissues show a regular dependence of the final concentration of AIV in the analyzed brain samples of animals treated with 12.5 and 25 mg/kg b.w. of AIV (0.00012299 and 0.0002306 mg, respectively, per one brain). Moreover, the AIV logBB value was experimentally determined and found to be equal to 0.49 ± 0.03.
机译：随着中枢神经系统（CNS）候选药物的数量不断增加，迫切需要对给药的化合物是否能够穿过血脑屏障（BBB）进行精确的先验预测。这项研究的目的是评估穿越根部三萜皂苷的血脑屏障的能力。该研究是通过计算机方法结合死后研究对分离的黄芪甲苷IV（AIV）处理的小鼠的脑组织进行的。首先，为了评估被测皂苷穿过血脑屏障的能力，建立了新的定量构效关系（QSAR）模型。基于血脑屏障穿透描述符（logBB）值，-辛醇/水与环己烷/水logP之差（ΔlogP），正辛醇/水分配系数的对数的模型的可靠性和可预测性（logP）和过量摩尔折光率（E）均使用适用范围（AD）确认。发现临界杠杆值h *为0.128。在这里研究了标准残差与杠杆之间的关系。体外乙酰胆碱酯酶抑制试验的应用表明，在被测化合物中，AIV被认为是最强的抑制剂。因此，使用半制备型HPLC（流动相由水，甲醇和乙酸乙酯组成（1.7：2.1：16.2 / /））将其分离出来，用于脑组织和血液的事后研究。在脑组织上进行的事后研究的结果表明，经分析的用12.5和25 mg / kg b.w处理的动物脑样本中AIV的最终浓度有规律的依赖性。 AIV（每只大脑0.00012299和0.0002306 mg）。此外，通过实验确定了AIV logBB值，发现其等于0.49±0.03。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号