title: Isoquercitrin Inhibits Hydrogen Peroxide-Induced Apoptosis of EA.hy926 Cells via the PI3K/Akt/GSK3β Signaling Pathway.
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.
authors.affiliation: Department of Pharmacy Shanxi, College of Traditional Chinese Medicine, No. 121 University Avenue, Taiyuan 030619, China. meixiaz032@163.com.|Shanxi Province Academy of Traditional Chinese Medicine, No. 46 Bingzhou West Road, Taiyuan 030012, China. meixiaz032@163.com.
authors.forename: Meixia
authors.initials: M
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, China. lijiankuan2004@163.com.
authors.forename: Jiankuan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacy Shanxi, College of Traditional Chinese Medicine, No. 121 University Avenue, Taiyuan 030619, China. wangk1758@163.com.|Shanxi Province Academy of Traditional Chinese Medicine, No. 46 Bingzhou West Road, Taiyuan 030012, China. wangk1758@163.com.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Shanxi Province Academy of Traditional Chinese Medicine, No. 46 Bingzhou West Road, Taiyuan 030012, China. hxliang-01@163.com.
authors.forename: Xuliang
authors.initials: X
authors.lastname: Hao
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, China. cpugr@126.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Ge
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, China. sxlqs2012@163.com.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta / Q000096:biosynthesis; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D009025:Morpholines / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002867:Chromones; D000071679:Glycogen Synthase Kinase 3 beta; D006861:Hydrogen Peroxide; D009025:Morpholines; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011794:Quercetin; C016527:isoquercitrin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: EA.hy926 cells; PI3K/Akt/GSK3β; apoptosis; isoquercitrin; oxidative stress