Activation of the Nrf2/HO-1 antioxidant pathway contributes to the protective effects of Lycium barbarum polysaccharides in the rodent retina after ischemia-reperfusion-induced damage.

Abstract

Lycium barbarum polysaccharides (LBP), extracts from the wolfberries, are protective to retina after ischemia-reperfusion (I/R). The antioxidant response element (ARE)-mediated antioxidant pathway plays an important role in maintaining the redox status of the retina. Heme oxygenase-1 (HO-1), combined with potent AREs in its promoter, is a highly effective therapeutic target for the protection against neurodegenerative diseases, including I/R-induced retinal damage. The aim of our present study was to investigate whether the protective effect of LBP after I/R damage was mediated via activation of the Nrf2/HO-1-antioxidant pathway in the retina. Retinal I/R was induced by an increase in intraocular pressure to 130 mm Hg for 60 minutes. Prior to the induction of ischemia, rats were orally treated with either vehicle (PBS) or LBP (1 mg/kg) once a day for 1 week. For specific experiments, zinc protoporphyrin (ZnPP, 20 mg/kg), an HO-1 inhibitor, was intraperitoneally administered at 24 h prior to ischemia. The protective effects of LBP were evaluated by quantifying ganglion cell and amacrine cell survival, and by measuring cell apoptosis in the retinal layers. In addition, HO-1 expression was examined using Western blotting and immunofluorescence analyses. Cytosolic and nuclear Nrf2 was measured using immunofluorescent staining. LBP treatment significantly increased Nrf2 nuclear accumulation and HO-1 expression in the retina after I/R injury. Increased apoptosis and a decrease in the number of viable cells were observed in the ganglion cell layer (GCL) and inner nuclear layer (INL) in the I/R retina, which were reversed by LBP treatment. The HO-1 inhibitor, ZnPP, diminished the LBP treatment-induced protective effects in the retina after I/R. Taken together, these results suggested that LBP partially exerted its beneficial neuroprotective effects via the activation of Nrf2 and an increase in HO-1 protein expression.

• Authors: Meihua He, Hong Pan, Raymond Chuen-Chung Chang, Kwok-Fai So, Nicholas C Brecha, Mingliang Pu
• Journal: PloS one (PLoS One) Vol. 9 Issue 1 Pg. e84800 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24400114 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Drugs, Chinese Herbal
• NF-E2-Related Factor 2
• Reactive Oxygen Species
• lycium barbarum polysaccharide
• Heme Oxygenase-1

Topics

• Amacrine Cells (drug effects, metabolism)
• Animals
• Apoptosis (drug effects)
• Cell Nucleus (metabolism)
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology)
• Enzyme Activation (drug effects)
• Gene Expression Regulation (drug effects)
• Heme Oxygenase-1 (genetics, metabolism)
• Lycium (chemistry)
• Male
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress (drug effects)
• Protein Transport
• Rats
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury
• Retina (drug effects, metabolism, pathology)
• Retinal Ganglion Cells (drug effects, metabolism, pathology)
• Signal Transduction (drug effects)