Astragaloside Ⅳ alleviates D-GAL-induced endothelial cell senescence by promoting mitochondrial autophagy via inhibiting the PINK1/Parkin pathway
YI Ming
LUO Ye
WU Lu
WU Zeheng
JIANG Cuiping
CHEN Shiyu
KE Xiao
Abstract：Objective 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.Conclusion AS-Ⅳ alleviates D-GAL-induced endothelial cell senescence by inhibiting the PINK1/Parkin pathway to regulate mitochondrial autophagy.
Keywords：astragalosidePINK1/Parkin signaling pathwaymitochondrial autophagyD-galactoseendothelial cellscellular senescence
Publication Date：2025-11-20
Online Publishing Date：2025-12-05(First online date of this platform, not the publication date of the document)
Pages：10( 2427-2436 )