Silymarin Ameliorates Diabetes-Induced Proangiogenic Response in Brain Endothelial Cells through a GSK-3 β Inhibition-Induced Reduction of VEGF Release

Diabetes mellitus (dm) is a major risk factor for cardiovascular disease. additionally,it was found to induce a dysfunctional angiogenic response in the brain that was attributed to oxidative stress. milk thistle seed extract (silymarin) has potent antioxidant properties,though its potential use in ameliorating diabetes-induced aberrant brain angiogenesis is unknown. glycogen synthase kinase-3β is a regulator of angiogenesis that is upregulated by diabetes. its involvement in diabetes-induced angiogenesis is unknown. to evaluate the potential of silymarin to ameliorate diabetes-induced aberrant angiogenesis,human brain endothelial cells (hbec-5i) were treated with 50 μg/ml advanced glycation end (age) products in the presence or absence of silymarin (50,100 μm). the angiogenic potential of hbec-5i was evaluated in terms of migration and in vitro tube formation capacities. the involvement of gsk-3β was also evaluated. age significantly increased the migration and tube formation rates of hbec-5i by about onefold (p=0.0001). silymarin reduced age-induced migration in a dose-dependent manner where 50 μm reduced migration by about 50%,whereas the 100 μm completely inhibited age-induced migration. similarly,silymarin 50 μg/ml blunted age-induced tube formation (p=0.001). this effect was mediated through a gsk-3β-dependent inhibition of vegf release. in conclusion,silymarin inhibits age-induced aberrant angiogenesis in a gsk-3β-mediated inhibition of vegf release. © 2017 ahmed alhusban et al.