Promotion of neurite outgrowth by 3,5,7,3ʹ,4ʹ-pentamethoxyflavone is mediated through ERK signaling pathway in Neuro2a cells

IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL
Shin-Ji Park, So-Young An, Yeon Jin An, Kyoung-Sook Kim, Hyunju Kim, Jong Hyun Cho, Young-Choon Lee
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Abstract

In this study, the effects of 3,5,7,3ʹ,4ʹ-pentamethoxyflavone (KP1), a major bioactive ingredient isolated from the Kaempferia parviflora rhizomes, on a neurite outgrowth in Neuro2a cells and its mechanism have been investigated. KP1 increased concentration-dependently the percentage of neurite-bearing cells. KP1 showed a remarkable capability to elicit neurite outgrowth in Neuro2a cells, as evidenced by morphological alterations and immunostaining using anti-class III β-tubulin and anti-NeuN antibodies. KP1 also displayed a higher neurogenic activity than retinoic acid (RA), a promoter of neurite outgrowth in Neuro2a cells. KP1 treatment caused significant elevation in phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and glycogen synthase kinase-3β (GSK-3β). However, KP1-triggered neurite outgrowth was markedly inhibited by treatment with the ERK inhibitor U0126, whereas p38 MAPK inhibitor SB203580 and GSK-3β inhibitor SB216763 did not influence KP1-induced neurite outgrowth. These results demonstrate that KP1 elicits neurite outgrowth and triggers cell differentiation of Neuro2a cells through ERK signal pathway.

Graphical abstract

Abstract Image

在 Neuro2a 细胞中,3,5,7,3',4'-五甲氧基黄酮通过 ERK 信号通路促进神经元的生长。
本研究探讨了从山奈根茎中分离出的一种主要生物活性成分--3,5,7,3ʹ,4ʹ-五甲氧基黄酮(KP1)对 Neuro2a 细胞神经元生长的影响及其机制。KP1 可增加神经元细胞的百分比,但与浓度无关。KP1 能显著诱导 Neuro2a 细胞的神经元生长,这一点可以通过形态学改变以及使用抗 III 类 β-微管蛋白和抗 NeuN 抗体进行免疫染色来证明。KP1 还显示出比视黄酸(RA)更高的神经源活性,视黄酸是 Neuro2a 细胞神经元生长的促进剂。KP1 处理会导致细胞外信号调节激酶(ERK)、p38 丝裂原活化蛋白激酶(p38 MAPK)和糖原合酶激酶-3β(GSK-3β)的磷酸化显著升高。然而,ERK抑制剂U0126能明显抑制KP1诱导的神经元生长,而p38 MAPK抑制剂SB203580和GSK-3β抑制剂SB216763则不影响KP1诱导的神经元生长。这些结果表明,KP1通过ERK信号通路诱导神经元外生并触发Neuro2a细胞的细胞分化。 图文摘要
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来源期刊
CiteScore
6.90
自引率
3.00%
发文量
79
审稿时长
1.7 months
期刊介绍: The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.
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