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基于 BSA 的姜黄素纳米粒子对成年小鼠记忆及海马 MMP-2、MMP-9 和 MAPKs 的影响。

The Effect of BSA-Based Curcumin Nanoparticles on Memory and Hippocampal MMP-2, MMP-9, and MAPKs in Adult Mice.

机构信息

Students Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Nanobiology and Nanomedicine Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

J Mol Neurosci. 2018 Jul;65(3):319-326. doi: 10.1007/s12031-018-1104-4. Epub 2018 Jun 24.

DOI:10.1007/s12031-018-1104-4
PMID:29938313
Abstract

Although high rate of curcumin consumption has been suggested to decrease the prevalence of Alzheimer's disease (AD), its administration has no effect on the progression of AD in humans and this has been attributed to its poor bioavailability. Using nanotechnology to break down curcumin increases its bioavailability and improves its effect on the brain. BSA, as a non-toxic protein with high binding capacity, was used to break curcumin to nanosize and to explore the effect of nanocurcumin on passive avoidance memory and hippocampal MMP-2 and -9 and MAPKs. BSA-based nanocurcumin was produced by desolvation method. In this study, 15 and 20 mg/kg/p.o. nanocurcumin (based on our preliminary studies) were administered to male NMRI mice weighing 20-25 g for 10 days. Passive avoidance training was performed on day 10 and 24 h after, a retention trial was done. Upon completion of behavioral studies, the hippocampi were isolated and western blot analysis was performed on MMP-2, MMP-9, and MAPKs (JNK, ERK, and p38). The results showed that BSA-based nanocurcumin administered at 15 and 20 mg/kg doses resulted in a significantly improved performance in passive avoidance memory test while its equivalent doses of natural curcumin did not produce a similar effect. In addition, this effect was accompanied with an increase in MMP-2, MMP-9, and p-ERK and a decrease in p-JNK. This study indicates that breaking curcumin to nanosize produces improved effects on passive avoidance memory in adult mice accompanied with MMP-2, MMP-9, p-ERK, and p-JNK changes in the hippocampus.

摘要

虽然高剂量的姜黄素摄入被认为可以降低阿尔茨海默病(AD)的患病率,但它对人类 AD 的进展没有影响,这归因于其生物利用度差。使用纳米技术将姜黄素分解可以提高其生物利用度并改善其对大脑的作用。BSA 作为一种具有高结合能力的无毒蛋白质,被用于将姜黄素分解为纳米尺寸,并探索纳米姜黄素对被动回避记忆以及海马 MMP-2 和 MMP-9 和 MAPKs 的影响。通过去溶剂法生产基于 BSA 的纳米姜黄素。在这项研究中,给体重为 20-25g 的雄性 NMRI 小鼠口服 15 和 20mg/kg/天的纳米姜黄素(基于我们的初步研究)10 天。在第 10 天进行被动回避训练,24 小时后进行保留试验。行为研究完成后,分离出海马并对 MMP-2、MMP-9 和 MAPKs(JNK、ERK 和 p38)进行 Western blot 分析。结果表明,BSA 基纳米姜黄素以 15 和 20mg/kg 剂量给药可显著改善被动回避记忆测试中的表现,而其等效剂量的天然姜黄素则没有产生类似的效果。此外,这种效果伴随着 MMP-2、MMP-9 和 p-ERK 的增加以及 p-JNK 的减少。这项研究表明,将姜黄素分解为纳米尺寸可提高成年小鼠的被动回避记忆效果,同时伴有海马 MMP-2、MMP-9、p-ERK 和 p-JNK 的变化。

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