Cytoprotective effects of berry anthocyanins against induced oxidative stress and inflammation in primary human diabetic aortic endothelial cells. (1st February 2020) - Aboonabi, Anahita
Abstract: Type 2 diabetes is associated with oxidative stress and low-grade inflammation resulting in endothelial dysfunction (ED). This study determined to explore the protective effects of berry-derived anthocyanins (AC) with potent antioxidant and anti-inflammatory activities in human diabetic endothelial cells upon oxidative and inflammatory stressors. Cultured healthy human aortic endothelial cells (HAEC) and diabetic human aortic endothelial cells (D-HAEC) exposed to oxidative stress by hydrogen peroxide (H2 O2, 75 μM) and lipopolysaccharide (LPS, 1 μg/mL) as an inflammatory inducer before treatment with AC (50 μl/ml). The results from cytotoxicity assays showed that AC had no significant effects in cell viability (P-value < 0.0001), and exposure to H2 O2 75 μM had a less toxic effect (P-value < 0.05). Although, AC significantly decreased H2 O2 -induced cytotoxicity and oxidative stress in both HAEC and D-HAEC cell lines (P-value < 0.0001), no positive impact of AC was found on the GSSG/GSH ratios (P-value < 0.05). Exposure to the LPS increased the production of IL-6 in both HAEC and D-HAEC cell lines (P-value < 0.0001), whereas AC treatment reduced LPS‐induced IL‐6 production in both cell lines with a more robust impact on D-HAEC (P-value < 0.0001). While LPS increased inflammasome assembling and caspase-1 activation, AC treatment inhibited caspase-1 activation in D-HAEC (P ≤ 0.05). This study indicated that berry anthocyanins reduced oxidative stress and inflammation via the inhibition of the NF-ƙB signaling pathway, which contributes to mitigating the diabetes-induced up-regulation of NF-ƙB. Highlights: T2DM is associated with oxidative stress and inflammation resulting in ED. Anthocyanins (AC) decreased H2 O2 -induced cytotoxicity in both HAEC & D-HAEC. AC reduced LPS‐induced IL‐6 production in the diabetic endothelial cell line. AC treatment inhibited LPS‐induced caspase-1 activation in D-HEAC. AC protected D-HAECs via anti-inflammatory mechanisms to prevent diabetic ED.