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Quercetin conjugated with superparamagnetic iron oxide nanoparticles improves learning and memory better than free quercetin via interacting with proteins involved in LTP

机译:槲皮素与超顺磁性氧化铁纳米颗粒共轭通过与LTP参与的蛋白质相互作用比游离槲皮素更好地改善学习和记忆

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摘要

Biomedical application of quercetin (QT) as an effective flavonoid has limitations due to its low bioavailability. Superparamagnetic iron oxide nanoparticle (SPION) is a novel drug delivery system that enhances the bioavailability of quercetin. The effect of short time usage of quercetin on learning and memory function and its signaling pathways in the healthy rat is not well understood. The aim of this study was to investigate the effect of free quercetin and in conjugation with SPION on learning and memory in healthy rats and to find quercetin target proteins involved in learning and memory using Morris water maze (MWM) and computational methods respectively. Results of MWM show an improvement in learning and memory of rats treated with either quercetin or QT-SPION. Better learning and memory functions using QT-SPION reveal increased bioavailability of quercetin. Comparative molecular docking studies show the better binding affinity of quercetin to RSK2, MSK1, CytC, Cdc42, Apaf1, FADD, CRK proteins. Quercetin in comparison to specific inhibitors of each protein also demonstrates a better QT binding affinity. This suggests that quercetin binds to proteins leading to prevent neural cell apoptosis and improves learning and memory. Therefore, SPIONs could increase the bioavailability of quercetin and by this way improve learning and memory.
机译:槲皮素(QT)作为有效的类黄酮的生物医学应用由于其生物利用度低而受到限制。超顺磁性氧化铁纳米粒子(SPION)是一种新型的药物递送系统,可增强槲皮素的生物利用度。短时间使用槲皮素对健康大鼠学习记忆功能及其信号传导途径的影响尚不清楚。这项研究的目的是研究游离槲皮素以及与SPION结合对健康大鼠学习和记忆的影响,并分别使用莫里斯水迷宫(MWM)和计算方法找到参与学习和记忆的槲皮素靶蛋白。 MWM的结果显示,用槲皮素或QT-SPION处理的大鼠的学习和记忆能力得到改善。使用QT-SPION更好的学习和记忆功能可显示槲皮素的生物利用度增加。比较的分子对接研究表明槲皮素与RSK2,MSK1,CytC,Cdc42,Apaf1,FADD,CRK蛋白具有更好的结合亲和力。与每种蛋白质的特异性抑制剂相比,槲皮素还表现出更好的QT结合亲和力。这表明槲皮素与蛋白质结合,从而阻止神经细胞凋亡并改善学习和记忆能力。因此,SPIONs可以增加槲皮素的生物利用度,从而改善学习和记忆能力。

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