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基于金属有机框架的新型分子印迹聚合物对三黄泻心汤中nNOS-PSD-95解偶联剂的快速选择性捕获建模

Modeling rapid and selective capture of nNOS-PSD-95 uncouplers from Sanhuang Xiexin decoction by novel molecularly imprinted polymers based on metal-organic frameworks.

作者信息

Pan Linli, Ding Yingying, Ni Xiaoting, Wang Chong-Zhi, Jiang Bo, Zhang Yu, Jiang Nan, Tang Yulin, Chen Lina, Yuan Chun-Su

机构信息

School of Pharmacy, Nanjing Medical University Nanjing Jiangsu 211166 China

Tang Center for Herbal Medicine Research, Department of Anesthesia & Critical Care, University of Chicago Chicago IL 60637 USA.

出版信息

RSC Adv. 2020 Feb 21;10(13):7671-7681. doi: 10.1039/c9ra10537a. eCollection 2020 Feb 18.

Abstract

Novel and highly selective molecularly imprinted polymers based on the surface of metal-organic frameworks, NH-MIL-101(Cr) (MIL@MIP), were successfully fabricated to capture neuronal nitric oxide synthase-postsynaptic density protein-95 (nNOS-PSD-95) uncouplers from Sanhuang Xiexin Decoction (SXD) for stroke treatment. The resultant polymers were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and X-ray diffraction. The performance tests revealed that MIL@MIPs had a large binding capacity, fast kinetics, and excellent selectivity. Then the obtained polymers were satisfactorily applied to solid-phase extraction coupled with high-performance liquid chromatography to selectively capture nNOS-PSD-95 uncouplers from SXD. Furthermore, the biological activities of components obtained from SXD were evaluated and . As a consequence, the components showed a potent neuroprotective effect from the MTS assay and uncoupling activity from the co-immunoprecipitation experiment. In addition, the anti-ischemic stroke assay was further investigated to determine the effect of reducing infarct size and ameliorating neurological deficit by the active components. Therefore, this present study contributes a valuable new method and new tendency to selectively capture active components for stroke treatment from SXD and other natural medicines.

摘要

基于金属有机框架NH-MIL-101(Cr)(MIL@MIP)表面成功制备了新型高选择性分子印迹聚合物,用于从治疗中风的三黄泻心汤(SXD)中捕获神经元型一氧化氮合酶-突触后致密蛋白95(nNOS-PSD-95)解偶联剂。通过傅里叶变换红外光谱、扫描电子显微镜、热重分析和X射线衍射对所得聚合物进行了表征。性能测试表明,MIL@MIPs具有较大的结合容量、快速的动力学和优异的选择性。然后将所得聚合物令人满意地应用于固相萃取结合高效液相色谱,以从SXD中选择性捕获nNOS-PSD-95解偶联剂。此外,还对从SXD中获得的成分的生物活性进行了评估。结果,这些成分在MTS试验中显示出强大的神经保护作用,在共免疫沉淀实验中显示出解偶联活性。此外,还进一步研究了抗缺血性中风试验,以确定活性成分减少梗死面积和改善神经功能缺损的效果。因此,本研究为从SXD和其他天然药物中选择性捕获用于中风治疗的活性成分提供了一种有价值的新方法和新趋势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/161f/9049783/a6a0aefa0578/c9ra10537a-f1.jpg

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