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Effects of bisdemethoxycurcumin promoting neuronal differentiation of neuroblastoma cells in mice and its mechanism
- ZHONGGUO YAOFANG Vol. 35, Issue 5, Pages: 578-583(2024)
- 作者机构：
1.南华大学衡阳医学院细胞与遗传研究所，湖南 衡阳 421001
2.湖南医药学院基础医学院，湖南 怀化 418000
3.脑与神经内分泌疾病湖南省高等学校重点实验室，湖南 怀化 418000
- 作者简介：
- 基金信息：
DOI：10.6039/j.issn.1001-0408.2024.05.12
CLC： R965Published：15 March 2024，
Received：19 August 2023，
Revised：03 November 2023，
扫 描 看 全 文
王嘉欣,房红志,吴敏等.双去甲氧基姜黄素对小鼠脑神经母瘤细胞的促神经分化作用及机制研究 Δ[J].中国药房,2024,35(05):578-583.
WANG Jiaxin,FANG Hongzhi,WU Min,et al.Effects of bisdemethoxycurcumin promoting neuronal differentiation of neuroblastoma cells in mice and its mechanism[J].ZHONGGUO YAOFANG,2024,35(05):578-583.
王嘉欣,房红志,吴敏等.双去甲氧基姜黄素对小鼠脑神经母瘤细胞的促神经分化作用及机制研究 Δ[J].中国药房,2024,35(05):578-583. DOI： 10.6039/j.issn.1001-0408.2024.05.12.
WANG Jiaxin,FANG Hongzhi,WU Min,et al.Effects of bisdemethoxycurcumin promoting neuronal differentiation of neuroblastoma cells in mice and its mechanism[J].ZHONGGUO YAOFANG,2024,35(05):578-583. DOI： 10.6039/j.issn.1001-0408.2024.05.12.
摘要
目的
2
研究姜黄素衍生物双去甲氧基姜黄素（BC）对小鼠脑神经母瘤细胞Neuro-2a（N2a）的促神经分化作用及机制。
方法
2
采用MTT法检测BC（1、2、4、6、8、10 μmol/L）对N2a细胞存活率的影响，确定药物处理浓度范围。设对照组、视黄酸（RA）组（10 μmol/L）和BC组（1、2、4 μmol/L），培养48、72 h后，对分化细胞的神经突起长度进行测量并计算细胞分化率；采用Western blot法检测4 μmol/L BC作用5、15、30、60、120 min后细胞中蛋白激酶B（Akt）、细胞外调节蛋白激酶1/2（ERK1/2）、p38丝裂原活化蛋白激酶（p38）蛋白的磷酸化水平。以抑制剂LY294002（LY）和PD98059（PD）干预后，进一步验证BC对Akt和ERK蛋白磷酸化水平及促神经分化的影响。
结果
2
根据MTT实验确定后续诱导细胞分化的BC浓度为1、2、4 μmol/L。分化48 h后，与对照组比较，RA组和BC 1、2、4 μmol/L组细胞分化率及BC 4 μmol/L组细胞神经突起长度均显著升高/增加（
P
＜0.05或
P
＜0.01）；BC继续诱导分化至72 h后，与对照组比较，RA组细胞分化率和神经突起长度、BC 4 μmol/L组细胞分化率和BC 2 μmol/L组细胞神经突起长度均显著升高/增加（
P
＜0.05或
P
＜0.01）。与0 min组比较，BC 4 μmol/L作用5、15、30、60、120 min组细胞中Akt、ERK1/2、p38蛋白的磷酸化水平均有不同程度升高，部分差异有统计学意义（
P
＜0.05或
P
＜0.01）。加入抑制剂LY/PD后，与BC组比较，PD+BC组细胞中ERK1/2蛋白的磷酸化水平显著降低（
P
＜0.01），LY组、LY+BC组、PD组、PD+BC组细胞分化率均显著降低（
P
＜0.01）。
结论
2
BC可以促进N2a细胞分化，增加细胞分化率和神经突起长度，其机制可能与激活MEK/ERK和PI3K/Akt信号通路有关。
Abstract
OBJECTIVE
2
To study the effects of the curcumin derivative bisdemethoxycurcumin （BC） promoting neuronal differentiation of neuroblastoma cells Neuro-2a （N2a） in mice and its mechanism.
METHODS
2
The effects of BC （1， 2， 4， 6， 8， 10 μmol/L） on the viability of N2a cells were detected by MTT assay to determine the concentration range of drug treatment. The control group， retinoic acid （RA） group （10 μmol/L） and BC groups （1， 2 and 4 μmol/L） were set up， and the length of neural protrusions of the differentiated cells was measured and the cell differentiation rate was calculated after 48 h and 72 h of culture. Compared with 0 min group， Western blot was used to detect the phosphorylation levels of protein kinase B （Akt）， extracellular-signal regulated kinase 1/2 （ERK1/2）， and p38 mitogen-activated protein kinase （p38） proteins in cells treated by 4 μmol/L BC for 5， 15， 30， 60， 120 min. After intervention with inhibitors LY294002 （LY） and PD98059 （PD）， the effects of BC on Akt and ERK1/2 protein phosphorylation levels and promoting neural differentiation were further validated.
RESULTS
2
According to the MTT experiment， the BC concentrations for subsequent induction of cell differentiation were determined to be 1， 2， and 4 μmol/L. After 48 hours of differentiation， compared with the control group， the cell differentiation rate in RA group and BC 1， 2 and 4 μmol/L groups， the length of cellular neural processes in the BC 4 μmol/L group significantly increased （
P
＜0.05 or
P
＜0.01）；after inducing differentiation of BC for 72 hours， compared with the control group， the cell differentiation rate and the length of cellular neural processes in the RA group， the cell differentiation rate in the BC 4 μmol/L group， and the length of cellular neural processes in the BC 2 μmol/L group all significantly increased （
P
＜0.05 or
P
＜0.01）.Compared with the 0 min group， the phosphorylation levels of Akt， ERK1/2， and p38 proteins in cells of the 5， 15， 30， 60 and 120 min groups increased to varying degrees after treated by 4 μmol/L BC， and some differences were statistically significant （
P
＜0.05 or
P
＜0.01）. After adding the inhibitor LY/PD， compared with the BC group， the phosphorylation level of ERK1/2 protein in the PD+BC group cells were significantly reduced （
P
＜0.01）， and the cell differentiation rates in the LY group， LY+BC group， PD group， and PD+BC group was significantly reduced （
P
＜0.01）.
CONCLUSIONS
2
BC promotes N2a cell differentiation mainly by increasing cell differentiation rate and neural protrusion length. The mechanism may be related to the activation of mitogen-activated protein kinase/ERK and PI3K/Akt signaling pathways.
关键词
双去甲氧基姜黄素脑神经母瘤细胞促神经分化阿尔茨海默病神经营养活性
Keywords
neuroblastoma cellpromoting neuronal differentiationAlzheimer’s diseaseneuro- trophic activity
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