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

Ahmed Alhusban,Enaam Alkhazaleh,Tamam El-Elimat

doi:10.1155/2017/2537216

Ahmed Alhusban, Enaam Alkhazaleh + Show 1 more

Open Access

https://doi.org/10.1155/2017/2537216

Copy DOI

Abstract

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.

Highlights

Diabetes mellitus (DM) is a wide-spread chronic metabolic disease characterized by elevated blood glucose either due to insulin resistance or insulin deficiency [1,2,3]
To investigate the ability of silymarin to directly alter the angiogenic potential of untreated HBEC-5i, a range of silymarin concentrations (0–200 μg/mL) was applied to HBEC-5i (Figures 1(a) and 1(b))
We assessed whether the effects of advanced glycation end (AGE) would mimic the effects of diabetes on the behavior of HBEC-5i

Summary

Introduction

Diabetes mellitus (DM) is a wide-spread chronic metabolic disease characterized by elevated blood glucose either due to insulin resistance (type II) or insulin deficiency (type I) [1,2,3]. Around 8.5% of adults aged 18 and older had elevated blood glucose in 2014 [4]. Diabetes mellitus is a well-known major risk factor for the development of cardiovascular disease, including coronary artery disease (CAD), stroke, and peripheral artery disease [1]. About 80% of deaths among diabetics are due to atherosclerosis-related diseases [6, 7]. The majority of diabetes-associated complications are caused by its effect on both small and large blood vessels. Diabetes was found to alter angiogenesis in a tissue-dependent manner [8]

Objectives

Methods

Results

Conclusion