title: Astragaloside IV improved barrier dysfunction induced by acute high glucose in human umbilical vein endothelial cells.
abstract: The purpose of the present study was to examine the effects of astragaloside IV, a saponin isolated from Astragalus membranaceus (Fisch) Bge, on the impairment of barrier function induced by acute high glucose in cultured human vein endothelial cells. High glucose (27.8 mM) induced a decrease in transendothelial electrical impedance and an increase in cell monolayer permeability in human umbilical vein endothelial cells. Endothelial barrier dysfunction stimulated by high glucose was accompanied by translocation and activation of protein kinase C (PKC), the redistribution of F-actin and formation of intercellular gaps, suggesting that increases in PKC activity and rearrangement of F-actin could be associated with endothelial barrier dysfunction induced by acute high glucose. Application of astragaloside IV inhibited high glucose-induced endothelial barrier dysfunction in a dose-dependent manner, which is compatible with inhibition of PKC translocation and improvement of F-actin rearrangements. Western blot analysis revealed that high glucose-induced PKC alpha and beta2 overexpression in the membrane fraction were significantly reduced by astragaloside IV. These findings indicate that astragaloside IV protected endothelial cells from high glucose-induced barrier impairment by inhibiting PKC activation, as well as improving cytoskeleton remodeling.
authors.affiliation: Department of Biomedical Engineering, Zhejiang University (Yuquan Campus), Hangzhou 310027, PR China.
authors.forename: Han-Bing
authors.initials: HB
authors.lastname: Li
authors.forename: Ya-Kun
authors.initials: YK
authors.lastname: Ge
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiao-Xiang
authors.initials: XX
authors.lastname: Zheng
mesh_terms: D000199:Actins / Q000378:metabolism; D000465:Algorithms; D017209:Apoptosis / Q000187:drug effects; D015824:Blood-Air Barrier / Q000187:drug effects*; D015153:Blotting, Western; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005947:Glucose / Q000633:toxicity*; D006801:Humans; D010590:Phalloidine; D011493:Protein Kinase C / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000199:Actins; D012503:Saponins; D014315:Triterpenes; D010590:Phalloidine; C052064:astragaloside A; D011493:Protein Kinase C; D005947:Glucose