Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki 305-8572, Japan.
Brain Res. 2012 Feb 9;1437:16-25. doi: 10.1016/j.brainres.2011.12.019. Epub 2011 Dec 16.
Luteolin, a 3', 4', 5, 7-tetrahydroxyflavone, is an active compound in Rosmarinus officinalis (Lamiacea), and has been reported to exert several benefits in neuronal cells. However cholinergic-induced activities of luteolin still remain unknown. Neuronal differentiation encompasses an elaborate developmental program which plays a key role in the development of the nervous system. The advent of several cell lines, like PC12 cells, able to differentiate in culture proved to be the turning point for gaining and understanding of molecular neuroscience. In this work, we investigated the ability of luteolin to induce PC12 cell differentiation and its effect on cholinergic activities. Our findings showed that luteolin treatment significantly induced neurite outgrowth extension, enhanced acetylcholinesterase (AChE) activity, known as neuronal differentiation marker, and increased the level of total choline and acetylcholine in PC12 cells. In addition, luteolin persistently, activated extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt; while the addition of pharmacological MEK/ERK1/2 inhibitor (U0126) and PI3k/Akt inhibitor (LY294002) attenuated luteolin-induced AChE activity and neurite outgrowth in PC12 cells. The above findings suggest that luteolin induces neurite outgrowth and enhanced cholinergic activities, at least in part, through the activation of ERK1/2 and Akt signaling.
木樨草素，一种 3'，4'，5，7-四羟基黄酮，是迷迭香（唇形科）中的一种活性化合物，据报道它对神经元细胞有多种益处。然而，木樨草素的胆碱能诱导活性仍然未知。神经元分化包括一个复杂的发育程序，它在神经系统的发育中起着关键作用。几种细胞系的出现，如 PC12 细胞，能够在培养中分化，这证明是分子神经科学的突破点。在这项工作中，我们研究了木樨草素诱导 PC12 细胞分化的能力及其对胆碱能活性的影响。我们的研究结果表明，木樨草素处理显著诱导了 PC12 细胞的突起延伸，增强了乙酰胆碱酯酶（AChE）活性，AChE 作为神经元分化的标志物，同时增加了 PC12 细胞中总胆碱和乙酰胆碱的水平。此外，木樨草素持续激活细胞外信号调节激酶 1/2（ERK1/2）和 Akt；而添加药理学 MEK/ERK1/2 抑制剂（U0126）和 PI3k/Akt 抑制剂（LY294002）则减弱了木樨草素诱导的 PC12 细胞 AChE 活性和突起延伸。上述发现表明，木樨草素通过激活 ERK1/2 和 Akt 信号通路诱导突起生长和增强胆碱能活性，至少部分是这样。
