title: Vaccarin attenuates high glucose-induced human EA•hy926 endothelial cell injury through inhibition of Notch signaling.
abstract: Endothelial cell injury is a critical component of atherosclerosis and hypertension. Vaccarin is considered to be of potential benefit in the treatment of vascular diseases. The aim of the present study was to evaluate the possible effects of vaccarin in human EA·hy926 cells induced by high glucose, and to investigate its underlying mechanism in the prevention and treatment of high glucose‑induced injury. In the present study, EA·hy926 cells were exposed to 90, 180 and 270 mM high glucose for 24 h, and the induced cell injury was examined using a sulforhodamine B assay. Following treatment with high glucose, it was found that high glucose stimulated cell injury, resulting in reduced cell viability and migratory ability, increased lactate dehydrogenase (LDH) leakage and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity. High glucose further accelerated cell apoptosis via activating Notch1 and Hairy and enhancer of split 1. It was found that preincubation with vaccarin protected the EA·hy926 cells from high glucose‑induced cell injury, which promoted cell viability and migratory ability, inhibited the expression levels of LDH and MDA, and enhanced the activity of SOD. Cell migratory ability, LDH leakage, MDA levels and decreasing SOD activity were evaluated using a wound healing assay and corresponding assay kits. Cell apoptosis was detected by flow cytometry with an Annexin V‑fluorescein isothiocyanate/propidium iodide apoptosis detection kit and Hoechst staining. Furthermore, western blotting was used to detect the protein expression levels of Notch1, Hes1 and caspase‑3. In particular, in addition to inducing the downregulation of Notch signaling, vaccarin treatment downregulated the cell apoptotic pathway‑associated protein caspase 3. These findings suggested that vaccarin may be able to selectively protect the vascular endothelium from dysfunction induced by high glucose.
authors.affiliation: Laboratory of Tumor Pharmacology, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Laboratory of Tumor Pharmacology, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Du
authors.affiliation: Laboratory of Natural Medicine, School of Pharmaceutical Science, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Fengshan
authors.initials: F
authors.lastname: Xie
authors.affiliation: Laboratory of Tumor Pharmacology, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Laboratory of Natural Medicine, School of Pharmaceutical Science, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Natural Medicine, School of Pharmaceutical Science, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Tumor Pharmacology, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.affiliation: Laboratory of Tumor Pharmacology, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Liying
authors.initials: L
authors.lastname: Qiu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000633:toxicity*; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072056:Transcription Factor HES-1 / Q000378:metabolism
chemical_list: D005419:Flavonoids; D006027:Glycosides; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C569886:vaccarin H; C078493:HES1 protein, human; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D053148:Caspase 3; D005947:Glucose