Rhein protects retinal Müller cells from high glucose-induced injury via activating the AMPK/Sirt1/PGC-1α pathway.

ABSTRACT

Oxidative stress, inflammation and apoptosis are important pathogenic factors of diabetic retinopathy (DR). In the current study, we aimed to evaluate the potential role of Rhein, a natural anthraquinone compound found in rhubarb, in high glucose (HG)-induced Müller cells (MIO-M1). Cell Counting Kit­8 assay, TUNEL assay, Western blot analysis, Reverse transcription quantitative polymerase chain reaction (RT-qPCR), and ELISA were conducted to assess the effects of Rhein on Müller cells. Additionally, the EX-527, an Sirt1 inhibitor, was used to study whether the effects of Rhein, on HG-induced Müller cells were mediated by activation of the Sirt1 signaling pathway. Our data showed that Rhein improved cell viability of HG-induced Müller cells. Rhein reduced the ROS and MDA production and increased the activities of SOD and CAT in Müller cells in response to HG stimulation. Rhein decreased the production of VEGF, IL-1ß, IL-6 and TNF-α. Moreover, Rhein attenuated HG-induced apoptosis, evidenced by increase in Bcl-2 level and decreases in the Bax, caspase-3 expression. It was also found that EX-527 counteracted Rhein-mediated anti-inflammatory, antioxidant and anti-apoptosis effects on Müller cells. The protein levels of p-AMPK and PGC-1α were also upregulated by Rhein. In conclusion, these findings support that Rhein may ameliorate HG-induced inflammation, oxidative stress, apoptosis and protect against mitochondrial dysfunction by the activation of the AMPK/Sirt1/PGC-1α signaling pathway.