Astragaloside IV alleviates D-GAL-induced endothelial cell senescence by promoting mitochondrial autophagy via inhibiting the PINK1/Parkin pathway.
10.12122/j.issn.1673-4254.2025.11.15
- Author:
Ming YI
1
;
Ye LUO
2
;
Lu WU
1
;
Zeheng WU
3
;
Cuiping JIANG
1
;
Shiyu CHEN
3
;
Xiao KE
3
Author Information
1. Department of Cardiology, Liuyang Hospital of Traditional Chinese Medicine (Second Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Hunan University of Chinese Medicine), Liuyang 410300, China.
2. Department of Cardiology, Peking University Shenzhen Hospital, Shenzhen 518057, China.
3. Department of Cardiology, Shenzhen Hospital of Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen 518057, China.
- Publication Type:Journal Article
- Keywords:
D-galactose;
PINK1/Parkin signaling pathway;
astragaloside;
cellular senescence;
endothelial cells;
mitochondrial autophagy
- MeSH:
Humans;
Human Umbilical Vein Endothelial Cells/drug effects*;
Cellular Senescence/drug effects*;
Autophagy/drug effects*;
Saponins/pharmacology*;
Ubiquitin-Protein Ligases/metabolism*;
Mitochondria/drug effects*;
Triterpenes/pharmacology*;
Protein Kinases/metabolism*;
Galactose/pharmacology*;
Reactive Oxygen Species/metabolism*;
Signal Transduction/drug effects*;
Cells, Cultured;
Apoptosis/drug effects*;
Membrane Potential, Mitochondrial;
Cell Proliferation/drug effects*
- From:
Journal of Southern Medical University
2025;45(11):2427-2437
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To explore the mechanism by which astragaloside IV (AS-IV) alleviates D-galactose (D-GAL)-induced senescence in human umbilical vein endothelial cells (HUVECs).
METHODS:Cultured HUVECs were treated with D-GAL (40 g/L), AS-IV (200 μmol/L), D-GAL+AS-IV, or D-GAL+AS-IV+MTK458 (a mitochondrial autophagy agonist, 25 μmol/L) for 48 h, and the changes in cell proliferation, migration, and angiogenesis capacity were evaluated. Cell apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and expressions of autophagy-related proteins (LC3-II/LC3-I) and PINK1/Parkin pathway proteins in the treated cells were detected.
RESULTS:AS-IV treatment significantly reduced the inhibitory effect of D-GAL on HUVEC viability, effectively alleviated D-GAL-induced impairment of tube-forming ability, and promoted angiogenesis and migration ability of the cells. AS-IV also significantly reduced the rate of D-GAL-induced HUVECs positive for senescence-associated β-galactosidase (SA-β-Gal) staining and inhibited the expression of senescence-related genes P21 and P53. AS-IV restored mitochondrial membrane potential and reduced intracellular ROS levels in D-GAL-induced HUVECs, and inhibited the fusion of autophagosomes and lysosomes to prevent the completion of autophagic flux. In HUVECs treated with both D-GAL and AS-IV, the application MTK458 significantly increased the number of yellow spots and enhanced the expressions of P21, P53, PINK1, Parkin, LC3, and Beclin proteins.
CONCLUSIONS:AS-IV alleviates D-GAL-induced endothelial cell senescence by inhibiting the PINK1/Parkin pathway to regulate mitochondrial autophagy.
