Effect of neferine on mitophagy in Parkinson’s disease cells

CHEN Cuiqing; TAN Chenchen; WANG Diancui; JIANG Min

doi:10.6039/j.issn.1001-0408.2025.02.11

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Effect of neferine on mitophagy in Parkinson’s disease cells

更新时间：2025-09-25

- Effect of neferine on mitophagy in Parkinson’s disease cells
- ZHONGGUO YAOFANG Vol. 36, Issue 2, Pages: 197-202(2025)
- 作者机构：
  
  1.康复大学青岛中心医院/青岛市中心医院神经内科，山东青岛　266042
  2.康复大学青岛中心医院/青岛市中心医院血液科，山东青岛　266042
  3.青岛市第六人民医院神经内科，山东青岛　266000
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.02.11
  CLC： R965;R742.5
- Received：04 July 2024，
  
  Revised：2024-12-24，
  
  Accepted：24 December 2024，
  
  Published：30 January 2025
- 稿件说明：
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陈翠青,谭臣臣,王电翠,等.甲基莲心碱对帕金森病细胞线粒体自噬的影响[J].中国药房,2025,36(02):197-202.

CHEN Cuiqing,TAN Chenchen,WANG Diancui,et al.Effect of neferine on mitophagy in Parkinson’s disease cells[J].ZHONGGUO YAOFANG,2025,36(02):197-202.
陈翠青,谭臣臣,王电翠,等.甲基莲心碱对帕金森病细胞线粒体自噬的影响[J].中国药房,2025,36(02):197-202. DOI： 10.6039/j.issn.1001-0408.2025.02.11.

CHEN Cuiqing,TAN Chenchen,WANG Diancui,et al.Effect of neferine on mitophagy in Parkinson’s disease cells[J].ZHONGGUO YAOFANG,2025,36(02):197-202. DOI： 10.6039/j.issn.1001-0408.2025.02.11.

摘要

目的

探究甲基莲心碱（NEF）调节腺苷一磷酸活化的蛋白激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）/UNC-51样激酶1（ULK1）信号通路对帕金森病（PD）细胞线粒体自噬的影响，从而探讨该药改善PD的作用机制。

方法

用100 μmol/L的1-甲基-4-苯基吡啶离子（MPP

）处理SH-SY5Y细胞24 h以构建PD细胞模型，将PD模型细胞分为模型组（PD组）和NEF低、中、高浓度处理组（NEF-L、NEF-M、NEF-H组，2.5、5.0、10.0 μmol/L）以及NEF高浓度+AMPK抑制剂组（NEF-H+Compound C组，10.0 μmol/L NEF和50 μmol/L Compound C）；另取未经MPP

、NEF处理的细胞作为对照组。观察各组细胞的超微形态，检测其自噬体数量、存活率、凋亡率、线粒体膜电位的变化情况，胱天蛋白酶3（Caspase-3）、微管相关蛋白1轻

链3（LC3）、Beclin-1蛋白的表达水平，以及mTOR、AMPK、ULK1蛋白的磷酸化水平。

结果

与PD组比较，NEF-L、NEF-M、NEF-H组细胞自噬体明显增多，膜电位有所升高，存活率、LC3-Ⅱ/LC3-Ⅰ、Beclin-1蛋白的表达和AMPK、ULK1蛋白的磷酸化水平均显著升高或上调，凋亡率和Caspase-3、p62蛋白的表达及mTOR蛋白的磷酸化水平均显著降低或下调，且上述改善作用均呈浓度依赖性（

＜0.05）；Compound C能显著逆转高浓度NEF的上述改善作用（

＜0.05）。

结论

NEF通过上调AMPK、ULK1蛋白的磷酸化水平，下调mTOR蛋白的磷酸化水平来促进PD模型细胞的线粒体自噬，抑制细胞凋亡，从而发挥神经细胞保护作用。

Abstract

OBJECTIVE

To investigate the effect of neferine （NEF） on mitophagy in Parkinson’s disease （PD） cells by regulating the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/UNC-51-like kinase 1 （ULK1） signaling pathway， and explore the mechanism of this drug to improve PD.

METHODS

SH-SY5Y cells were treated with 100 μmol/L 1-methyl-4-phenylpyridinium ion （MPP

） for 24 h to construct a PD cell model. PD model cells were divided into model group （PD group）， NEF low-， medium- and high-concentration groups （NEF-L， NEF-M， NEF-H group， 2.5， 5.0， 10.0 μmol/L）， and high concentration of NEF+AMPK inhibitor group （NEF-H+Compound C group， 10.0 μmol/L NEF+50 μmol/L Compound C）. The cells treated without MPP

and NEF were used as the control group. The ultrastructure of the cells in each group was observed； the amount of autophagosomes， survival rate， apoptosis rate， mitochondrial membrane potential， and the protein expressions of Caspase-3， microtubule-associated protein 1 light chain 3 （LC3） and Beclin-1， as well as the phosphorylation levels of mTOR， AMPK and ULK1 were detected.

RESULTS

Compared with PD group， the amount of autophagosomes in NEF-L， NEF-M and NEF-H groups was increased， and membrane potential was increased； survival rate， LC3-Ⅱ/LC3-Ⅰ， protein expression of Beclin-1， and protein phosphorylation levels of AMPK and ULK1 were significantly increased or up-regulated； the

apoptotic rate， protein expressions of Caspase-3 and p62， and protein phosphorylation level of mTOR were significantly decreased or down-regulated， and the above improvements were in a dose-dependent manner （

＜0.05）. Compound C could significantly reverse the above improvement effect of high concentration of NEF （

＜0.05）.

CONCLUSIONS

NEF can promote mitophagy and inhibit apoptosis of PD model cells by up-regulating protein phosphorylation levels of AMPK and ULK1， and down-regulating protein phosphorylation level of mTOR， thus playing a protective role in nerve cells.

关键词

Keywords

references

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