Mechanism of ellagic acid on mitophagy of endothelial cells under high-glucose environment based on PINK1/Parkin signaling pathway
YAN Jie
CHEN Kaiqin
LI Ting
ZHU Furong
Abstract：Objective To explore whether ellagic acid(EA)affects mitophagy in endothelial cells under high glu-cose environment by regulating the PTEN-induced kinase 1(PINK1)/Parkin signaling pathway.Methods EA-hy926 cells(human umbilical vein endothelial cells)in the logarithmic growth phase were randomly divided into the control group,model group,and EA group,with 3 replicate wells in each group.The model group and EA group were cultured in DMEM medium containing 50 mmol/L glucose for 24 h to establish the high glucose-induced endothelial cell injury mod-els.The EA group was further cultured for 24 h after adding 40 nmol/L EA working solution,while the control group re-ceived no treatment.At 24 h of culture,CCK-8 assay was used to detect cell proliferation activity,tube formation assay was performed to observe cell tube formation ability,transmission electron microscopy was used to observe mitochondrial structure,Western blotting was applied to detect PINK1 and Parkin proteins,and molecular docking analysis was used to evaluate the binding between EA and PINK1.Results Compared with the control group,the model group showed lower cell survival rate and shorter total lumen length(both P<0.05).Compared with the model group,the EA group had higher cell survival rate and longer total lumen length(both P<0.05).Compared with the control group,the model group exhibit-ed mitochondrial swelling,cristae loss,and vacuolization.In contrast,most mitochondria in the EA group showed re-paired damaged cristae,alleviated vacuolization,and a near-normal morphological structure.The relative expression lev-els of PINK1 and Parkin proteins in the model group were significantly lower than those in the control group(both P<0.05),while those in the EA group were significantly higher than those in the model group(both P<0.05).The binding energy between EA and PINK1 was-11.5 kcal/mol,and EA formed 6 hydrogen bonds with amino acid residues of PINK1 protein.Conclusion EA may promote mitophagy in EA-hy926 cells under high glucose environment by up-regulating the PINK1/Parkin signaling pathway,thereby improving cell proliferation activity and tube formation ability.
Keywords：ellagic acidPink1/parkin signaling pathwaymitophagyhigh glucoseendothelial cells
Publication Date：2025-12-25
Online Publishing Date：2026-01-12(First online date of this platform, not the publication date of the document)
Pages：4( 7-10 )