Purpose: Curcumin, a polyphenol isolated from the rhizomes of turmeric, holds great potential as a neuroprotective agent in addition to its anti-inflammatory and antioxidant characteristics. The poor bioavailability and low stability of curcumin are the greatest barriers to its clinical use. This study aims to investigate the neuroprotective effect of curcumin on axonal injury, by delivering the lipophilic polyphenol to a primary hippocampal neuron culture by means of a lipid-based drug delivery system, named emulsomes.
Methods: To study neuroregeneration ex vivo, an injury model was established through single-cell laser axotomy on hippocampal neurites. Upon treatment with curcumin-loaded emulsomes (CurcuEmulsomes), curcumin and CurcuEmulsome uptake into neurons was verified by three-dimensional Z-stack images acquired with confocal microscopy. Neuron survival after axonal injury was tracked by propidium iodide (PI) and Hoechst staining. Alterations in expression levels of physiological markers, such as anti-apoptotic marker Bcl2, apoptotic marker cleaved caspase 3, neuroprotective marker Wnt3a and the neuronal survival marker mTOR, were investigated by immunocytochemistry analyses.
Results: The results indicated significant improvement in the survival rate of injured neurons upon CurcuEmulsome treatment. Bcl2 expression was significantly higher for injured neurons treated with curcumin or CurcuEmulsome. Reduction in caspase 3 expression was seen in both curcumin and CurcuEmulsome treatment, whereas there were no significant changes in Wnt3a and mTOR expression.
Conclusion: The established laser-axotomy model was proven as a reliable methodology to study neurodegenerative models ex vivo. CurcuEmulsomes delivered curcumin to primary hippocampal neurons successfully. Treated with CurcuEmulsomes, injured hippocampal neurons benefit from the neuroprotective effects of curcumin, exhibiting a higher survival rate and increased anti-apoptotic marker levels.

Keywords: curcumin, lipid-based nanodrug delivery, neurodegeneration, hippocampus, axon injury


中文翻译：

---

加载姜黄素的乳化体在激光轴切术诱导的中枢神经系统损伤模型中的神经保护作用

目的：姜黄素是一种从姜黄根茎中分离出来的多酚，除了具有抗炎和抗氧化特性外，还具有作为神经保护剂的巨大潜力。姜黄素生物利用度差、稳定性低是其临床应用的最大障碍。本研究旨在研究姜黄素对轴突损伤的神经保护作用，通过一种名为 emulsomes 的基于脂质的药物递送系统将亲脂性多酚递送至原代海马神经元培养物。
方法：为了研究离体神经再生，通过单细胞激光轴切开海马神经突建立了损伤模型。在用载有姜黄素的乳化体 (CurcuEmulsomes) 处理后，姜黄素和姜黄乳化体摄取到神经元中通过用共聚焦显微镜获得的三维 Z 堆栈图像进行了验证。通过碘化丙啶 (PI) 和赫斯特染色跟踪轴突损伤后的神经元存活率。通过免疫细胞化学分析研究生理标志物表达水平的变化，例如抗凋亡标志物 Bcl2、凋亡标志物裂解的半胱天冬酶 3、神经保护标志物 Wnt3a 和神经元存活标志物 mTOR。
结果：结果表明 CurcuEmulsome 治疗后受损神经元的存活率显着提高。对于用姜黄素或 CurcuEmulsome 处理的受损神经元，Bcl2 表达显着更高。在姜黄素和 CurcuEmulsome 处理中均观察到 caspase 3 表达减少，而 Wnt3a 和 mTOR 表达没有显着变化。
结论：已建立的激光轴索切断模型被证明是一种可靠的方法来研究离体神经退行性模型。CurcuEmulsomes 成功地将姜黄素递送至原代海马神经元。用姜黄素治疗，受损的海马神经元受益于姜黄素的神经保护作用，表现出更高的存活率和增加的抗凋亡标志物水平。

关键词：姜黄素, 基于脂质的纳米药物递送, 神经变性, 海马, 轴突损伤