Blueberry anthocyanins extract attenuated diabetic retinopathy by inhibiting endoplasmic reticulum stress via the miR-182/OGG1 axis.

BACKGROUND: Previous studies have found that blueberry anthocyanin extract (BAE) could prevent diabetic retinopathy (DR) development, but the underlying molecular mechanism is still a mystery. METHODS: Human retinal pigment epithelium cell line ARPE-19 cells were exposed to high concentration glucose (H-Glu) with 25 mM for 24 h, and the cell viability and apoptosis were analyzed by MTT assay and flow cytometry, respectively. The endoplasmic reticulum stress (ERS) markers were determined by western blotting. Dual luciferase assay was applied to investigate the relationship between miR-182 and 8-oxoguanine-DNA glycosylase (OGG1). Furthermore, experiments in vivo were also performed to confirm the function of BAE in DR. RESULTS: The increase of apoptosis, reactive oxygen species (ROS) level and ERS in ARPE-19 cells induced by H-Glu was notably restored by BAE. Meanwhile, BAE greatly inhibited H-Glu-induced miR-182 expression in ARPE-19 cells, and OGG1 was identified to be one of the downstream target moleculars of miR-182. Furthermore, miR-182 overexpression or OGG1 knockdown restored the impact of BAE on H-Glu-treated APRE-19 cells. Even more important, BAE was further confirmed to alleviated the development of DR in diabetes rat models. CONCLUSIONS: BAE significantly inhibited the progression of DR via molecular regulation function between miR-182/OGG1 axis and ROS/ERS.

Changes of metabolites of acrylamide and glycidamide in acrylamide-exposed rats pretreated with blueberry anthocyanins extract.

Blueberry anthocyanins extract (BAE) is widely used natural antioxidant. The inhibitory effect of BAE (175 mg/kg bw/day) pretreatment on glycidamide (GA) metabolism following acrylamide (AA) (35 mg/kg bw/day) gavage for consecutive 7 days and 14 days in SD rat model were investigated in this work. AA, GA and its metabolites in urine, blood and 3 tissues were quantified using UPLC-MS/MS, respectively. The results showed pretreatment with BAE could significantly block the epoxidation of AA to GA. Compared with the control, BAE pretreatment significantly decreased the amount of GA and its mercapturic acid metabolite N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)-cysteine (GAMA3) in rats urine (p < 0.05), and sharply decreased the accumulation of GA DNA adduct N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GA-Gua) in liver, kidney and lung (p < 0.05). Meanwhile, significant reduction (p < 0.05) of N-(2-carbamoyl-2-hydroxyethyl) valine (GA-VAL) content was found in erythrocyte of the rats treated with BAE. This study provides a novel evidence for elucidating the chemopreventive effect of BAE on AA toxicity.