Flavonoids from seabuckthorn protect endothelial cells (EA.hy926) from oxidized low-density lipoprotein induced injuries via regulation of LOX-1 and eNOS expression.
The present investigation was undertaken to determine the protective effects of flavonoids from seabuckthorn (FSBT), a traditional Chinese medicine, on endothelial cell line EA.hy926 injury induced by oxidized low-density lipoprotein (ox-LDL). Possible mechanisms were then explored. The effects of quercetin and isorhamnetin, 2 major components of FSBT, were examined as well. Indices such as cell viability, lactate dehydrogenase, nitric oxide (NO), superoxide dismutase, and superoxide were measured. Reverse transcription polymerase chain reaction, Western blot, and immunocytochemistry were employed to determine the endothelial constitutive NO synthase (eNOS) and lectinlike low-density lipoprotein receptor-1 (LOX-1) expression. Cell viability decreased significantly after 24 hours treatment with ox-LDL, accompanied with apparent secretion disorders such as NO reduction and lactate dehydrogenase increase. FSBT pretreatment could remarkably prevent both cell death and secretion disorders in a concentration-dependent manner. Besides, it was observed that ox-LDL triggered superoxide production and suppressed the superoxide dismutase activity, both of which could be prevented by FSBT pretreatment. Moreover, ox-LDL inhibited eNOS expression and increased LOX-1 expression, whereas FSBT pretreatment partly abolished these effects. Similar effects were obtained with quercetin and isorhamnetin, implying that they may contribute, at least in part, to the protective effects of FSBT. The data indicate that the protective effects of FSBT against ox-LDL induced endothelial cell injuries might derive from its antioxidant activity and its capability in modulating the expression of eNOS and LOX-1. And quercetin and isorhamnetin may contribute to these effects of FSBT.
Bao
Meihua
M
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310031, China.
Lou
Yijia
Y
D001713:Biphenyl Compounds / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D044948:Flavonols / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D031281:Hippophae / Q000737:chemistry*; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010851:Picrates; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology / Q000031:analogs & derivatives; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D001713:Biphenyl Compounds; D005419:Flavonoids; D044948:Flavonols; D016166:Free Radical Scavengers; D006834:Hydrazines; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D010851:Picrates; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; C047368:3-methylquercetin; D009569:Nitric Oxide; D011794:Quercetin; C004931:1,1-diphenyl-2-picrylhydrazyl; D007770:L-Lactate Dehydrogenase; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase