1. Isoquercitrin Inhibits Hydrogen Peroxide-Induced Apoptosis of EA.hy926 Cells via the PI3K/Akt/GSK3β Signaling Pathway
- Author
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Xu-Liang Hao, Jiankuan Li, Rui Ge, Qingshan Li, Ke Wang, and Mei-Xia Zhu
- Subjects
0301 basic medicine ,Cell Survival ,Morpholines ,Pharmaceutical Science ,Biology ,medicine.disease_cause ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:Organic chemistry ,Annexin ,Drug Discovery ,medicine ,Humans ,oxidative stress ,isoquercitrin ,LY294002 ,EA.hy926 cells ,Physical and Theoretical Chemistry ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Phosphoinositide-3 Kinase Inhibitors ,Glycogen Synthase Kinase 3 beta ,Organic Chemistry ,apoptosis ,Endothelial Cells ,Hydrogen Peroxide ,Molecular biology ,PI3K/Akt/GSK3β ,Oncogene Protein v-akt ,030104 developmental biology ,Gene Expression Regulation ,chemistry ,Chromones ,Chemistry (miscellaneous) ,Apoptosis ,030220 oncology & carcinogenesis ,Molecular Medicine ,Phosphorylation ,Quercetin ,Signal transduction ,Oxidative stress ,Signal Transduction - Abstract
Oxidative stress plays a critical role in endothelial injury and the pathogenesis of diverse cardiovascular diseases, including atherosclerosis. Isoquercitrin (quercetin-3-glucoside), a flavonoid distributed widely in plants, exhibits many biological activities, including anti-allergic, anti-viral, anti-inflammatory, and anti-oxidative effects. In the present study, the inhibitory effect of isoquercitrin on H2O2-induced apoptosis of EA.hy926 cells was evaluated. MTT assays showed that isoquercitrin significantly inhibited H2O2-induced loss of viability in EA.hy926 cells. Hoechst33342/PI and Annexin V-FITC/PI fluorescent double staining indicated that isoquercitrin inhibited H2O2-induced apoptosis of EA.hy926 cells. Western blotting demonstrated that isoquercitrin prevented H2O2-induced increases in cleaved caspase-9 and cleaved caspase-3 expression, while increasing expression of anti-apoptotic protein Mcl-1. Additionally, isoquercitrin significantly increased the expression of p-Akt and p-GSK3β in a dose-dependent manner in EA.hy926 cells. LY294002, a PI3K/Akt inhibitor, inhibited isoquercitrin-induced GSK3β phosphorylation and increase of Mcl-1 expression, which indicated that regulation of isoquercitrin on Mcl-1 expression was likely related to the modulation of Akt activation. These results demonstrated that the anti-apoptotic effect of isoquercitrin on H2O2-induced EA.hy926 cells was likely associated with the regulation of isoquercitrin on Akt/GSK3β signaling pathway and that isoquercitrin could be used clinically to interfere with the progression of endothelial injury-associated cardiovascular disease.
- Published
- 2016