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Molecules. 2017 Dec 18;22(12). pii: E2251. doi: 10.3390/molecules22122251.

The Benefits of the Citrus Flavonoid Diosmin on Human Retinal Pigment Epithelial Cells under High-Glucose Conditions.

Author information

1
Department of Urology, Jen-Ai Hospital, Taichung City 41625, Taiwan. waynedoctor@gmail.com.
2
Center for Basic Medical Science, College of Health Science, Central Taiwan University of Science and Technology, Taichung City 40601, Taiwan. waynedoctor@gmail.com.
3
Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung County 90741, Taiwan. ssliou@tajen.edu.tw.
4
Department of Biotechnology, College of Pharmacy and Health Care, Tajen University, Pingtung County 90741, Taiwan. tyhong@tajen.edu.tw.
5
Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung County 90741, Taiwan. iml@tajen.edu.tw.

Abstract

We investigate diosmin for its effect on the ARPE-19 human retinal pigment epithelial cells exposed to high glucose, a model of diabetic retinopathy (DR). After incubation for 4 days with a normal (5 mmol/L) concentration of D-glucose, ARPE-19 cells were exposed separately to normal or high concentrations of D-glucose (30 mmol/L) with or without diosmin at different concentrations (0.1, 1, 10 μg/mL) for another 48 h. Next, we assessed cell viability, reactive oxygen species (ROS) generation and antioxidant enzyme activities. In order to examine the underlying molecular mechanisms, we meanwhile analyzed the expressions of Bax, Bcl-2, total and phosphorylated JNK and p38 mitogen-activated protein kinase (MAPK). Diosmin dose dependently enhanced cell viability following high glucose treatment in ARPE-19 cells. The activities of superoxide dismutase and glutathione peroxidase, as well as the levels of reduced glutathione were decreased, while it was observed that levels of ROS in high glucose cultured ARPE-19 cells increased. High glucose also disturbed Bax and Bcl-2 expression, interrupted Bcl-2/Bax balance, and triggered subsequent cytochrome c release into the cytosol and activation of caspase-3. These detrimental effects were ameliorated dose dependently by diosmin. Furthermore, diosmin could abrogate high glucose-induced apoptosis as well as JNK and P38 MAPK phosphorylation in ARPE-19 cells. Our results suggest that treatment ARPE-19 cells with diosmin halts hyperglycemia-mediated oxidative damage and thus this compound may be a candidate for preventing the visual impairment caused by DR.

KEYWORDS:

MAPK; ROS; diabetic retinopathy; diosmin; high glucose; human retinal pigment epithelial cells

PMID:
29258224
PMCID:
PMC6149669
DOI:
10.3390/molecules22122251
[Indexed for MEDLINE]
Free PMC Article

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