Effect of neferine on mitophagy in Parkinson's disease cells
10.6039/j.issn.1001-0408.2025.02.11
- VernacularTitle:甲基莲心碱对帕金森病细胞线粒体自噬的影响
- Author:
Cuiqing CHEN
1
;
Chenchen TAN
;
Diancui WANG
;
Min JIANG
Author Information
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
- Publication Type:Journal Article
- Keywords:
neferine;
Parkinson's disease;
mitophagy;
AMPK/mTOR/ULK1 signaling pathway
- From:
China Pharmacy
2025;36(2):197-202
- CountryChina
- Language:Chinese
-
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+50μmol/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(P＜0.05).Compound C could significantly reverse the above improvement effect of high concentration of NEF(P＜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.
