Antioxidant and Anti-Inflammatory Effects of Blueberry Anthocyanins on High Glucose-Induced Human Retinal Capillary Endothelial Cells

Abstract

Blueberries possess abundant anthocyanins, which benefit eye health. The purpose of this study was to explore the protective functional role of blueberry anthocyanin extract (BAE) and its predominant constituents, malvidin (Mv), malvidin-3-glucoside (Mv-3-glc), and malvidin-3-galactoside (Mv-3-gal), on high glucose- (HG-) induced injury in human retinal capillary endothelial cells (HRCECs). The results showed that BAE, Mv, Mv-3-glc, and Mv-3-gal enhanced cell viability (P < 0.05 versus the HG group at 24 h); decreased the reactive oxygen species (ROS, P < 0.01 versus the HG group both at 24 and 48 h); and increased the enzyme activity of catalase (CAT) and superoxide dismutase (SOD) (P < 0.05 versus the HG group both at 24 and 48 h). Mv could greatly inhibit HG-induced Nox4 expression both at 24 and 48 h (P < 0.05), while BAE and Mv-3-gal downregulated Nox4 only at 48 h (P < 0.05). Mv, Mv-3-glc, and Mv-3-gal also changed nitric oxide (NO) levels (P < 0.05). BAE and Mv-3-glc also influenced angiogenesis by decreasing the vascular endothelial cell growth factor (VEGF) level and inhibiting Akt pathway (P < 0.05). Moreover, Mv and Mv-3-glc inhibited HG-induced intercellular adhesion molecule-1 (ICAM-1, P < 0.001) and nuclear factor-kappa B (NF-κB) (P < 0.05). It indicated that blueberry anthocyanins protected HRCECs via antioxidant and anti-inflammatory mechanisms, which could be promising molecules for the development of nutraceuticals to prevent diabetic retinopathy.

Exploring the Applications of the Photoprotective Properties of Anthocyanins in Biological Systems

“…In vitro studies on Maqui berry extract have shown that it can protect the retinal cells against light-induced photoreceptor degeneration due to its content of anthocyanins [ 105 ]. Malvidin and its glycosides increase SOD and catalase in high glucose-induced human retinal capillary endothelial cells, protecting these cells from oxidative stress-induced damage, and by anti-inflammatory properties due to inhibition of ICAM-1 and NF-κβ [ 106 ].…”

The Coming Age of Flavonoids in the Treatment of Diabetic Complications

“…An in vitro study performed in human retinal capillary endothelial cells exposed to high glucose concentrations demonstrated that blueberry anthocyanin extracts reduced VEGF by inhibiting the Akt pathway. This anti-angiogenic effect was accompanied by an improvement in the oxidative and inflammatory state, evidenced by increased antioxidant enzymes (SOD and CAT) and reduced pro-oxidant enzymes (Nox4 and eNOS) and NF-κB activity [85]. Moreover, anti-inflammatory and anti-oxidant effects have also been demonstrated by myricetin, eriodyctiol and galangin in retinal epithelial, ganglial and microglial cells, respectively [84,86,87].…”

Anthocyanins as Antidiabetic Agents—In Vitro and In Silico Approaches of Preventive and Therapeutic Effects

“…In addition, the potential antidiabetic properties of intact anthocyanins could also be partly related to their antioxidant and anti-inflammatory activities. Anthocyanins may decrease the levels of reactive oxygen species, increase the enzyme activity of catalase and superoxide dismutase [ 36 ], and may influence angiogenesis by decreasing the vascular endothelial cell growth factor (VEGF) level and inhibiting the protein kinase B (Akt) pathway [ 36 ]. In particular, anthocyanins interact with the NF-κB and activator protein-1 (AP-1) signal transduction pathways, which respond to oxidative signals and mediate a proinflammatory effect, and the nuclear erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway and its regulated cytoprotective proteins (Glutathione S-transferase (GST), NADPH quinone oxidoreductase-1 (NQO-1), Heme oxygenase-1 (HO-1), etc.…”