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

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 M_uller cells (MIO-M1). Cell Counting Kit-8 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 M_uller cells. Additionally, the EX-527, an Sirt1 inhibitor, was used to study whether the effects of Rhein, on HG-induced M_uller cells were mediated by activation of the Sirt1 signaling pathway. Our data showed that Rhein improved cell viability of HG-induced M_uller cells. Rhein reduced the ROS and MDA production and increased the activities of SOD and CAT in M_uller cells in response to HG stimulation. Rhein decreased the production of VEGF, IL-1 beta, IL-6 and TNF-alpha. 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 M_uller cells. The protein levels of p-AMPK and PGC-1 alpha 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-1 alpha signaling pathway.