School of Integrative and Global Majors, University of Tsukuba, Tsukuba 305-8572, Japan.
Nipoo Co., Ltd., Osaka 574-0062, Japan.
Int J Mol Sci. 2022 Dec 1;23(23):15120. doi: 10.3390/ijms232315120.
Sugarcane ( L.) is a tropical plant grown for sugar production. We recently showed that sugarcane top (ST) ameliorates cognitive decline in a mouse model of accelerated aging via promoting neuronal differentiation and neuronal energy metabolism and extending the length of the astrocytic process in vitro. Since the crude extract consists of multicomponent mixtures, it is crucial to identify bioactive compounds of interest and the affected molecular targets. In the present study, we investigated the bioactivities of major polyphenols of ST, namely 3--caffeoylquinic acid (3CQA), 5--caffeoylquinic acid (5CQA), 3--feruloylquinic acid (3FQA), and Isoorientin (ISO), in human fetal neural stem cells (hNSCs)- an in vitro model system for studying neural development. We found that multiple polyphenols of ST contributed synergistically to stimulate neuronal differentiation of hNSCs and induce mitochondrial activity in immature astrocytes. Mono-CQAs (3CQA and 5CQA) regulated the expression of cyclins related to G1 cell cycle arrest, whereas ISO regulated basic helix-loop-helix transcription factors related to cell fate determination. Additionally, mono-CQAs activated p38 and ISO inactivated GSK3β. In hNSC-derived immature astrocytes, the compounds upregulated mRNA expression of PGC-1α, a master regulator of astrocytic mitochondrial biogenesis. Altogether, our findings suggest that synergistic interactions between major polyphenols of ST contribute to its potential for neuronal differentiation and astrocytic maturation.
甘蔗（L.）是一种热带植物，用于生产糖。我们最近表明，甘蔗顶（ST）通过促进神经元分化和神经元能量代谢以及体外延长星形胶质细胞过程的长度，改善了加速衰老小鼠模型的认知能力下降。由于粗提取物由多种成分混合物组成，因此确定感兴趣的生物活性化合物和受影响的分子靶标至关重要。在本研究中，我们研究了 ST 的主要多酚，即 3--咖啡酰奎宁酸（3CQA）、5--咖啡酰奎宁酸（5CQA）、3--阿魏酰奎宁酸（3FQA）和 Isoorientin（ISO），在人胎儿神经干细胞（hNSC）中的生物活性 - 一种用于研究神经发育的体外模型系统。我们发现 ST 的多种多酚协同作用刺激 hNSC 的神经元分化，并诱导不成熟星形胶质细胞中的线粒体活性。单 CQAs（3CQA 和 5CQA）调节与 G1 细胞周期阻滞相关的细胞周期蛋白的表达，而 ISO 调节与细胞命运决定相关的碱性螺旋-环-螺旋转录因子。此外，单 CQAs 激活了 p38，而 ISO 使 GSK3β失活。在 hNSC 衍生的不成熟星形胶质细胞中，这些化合物上调了 PGC-1α 的 mRNA 表达，PGC-1α 是星形胶质细胞线粒体生物发生的主要调节因子。总之，我们的研究结果表明，ST 的主要多酚之间的协同相互作用有助于其神经元分化和星形胶质细胞成熟的潜力。
