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Rhein protects retinal Müller cells from high glucose-induced injury via activating the AMPK/Sirt1/PGC-1α pathway
Cong Liu1,2, Qian Cao2, Yueqin Chen3
1Department of Ophthalmology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
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 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 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-1β, 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.
Insights
Rhein, a compound from rhubarb, protects against diabetic retinopathy by reducing inflammation, oxidative stress, and cell death in Müller cells. It activates the AMPK/Sirt1/PGC-1α pathway, offering potential therapeutic benefits.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Diabetic retinopathy (DR) pathogenesis involves oxidative stress, inflammation, and apoptosis.
- Müller cells play a critical role in retinal homeostasis and are affected by high glucose (HG).
Purpose of the Study:
- To investigate the protective effects of Rhein on high glucose-induced Müller cells (MIO-M1).
- To elucidate the role of the Sirt1 signaling pathway in Rhein's mechanism of action.
Main Methods:
- Cell Counting Kit-8, TUNEL assay, Western blot, RT-qPCR, and ELISA were used.
- Müller cells were treated with high glucose and Rhein, with or without the Sirt1 inhibitor EX-527.
- Key markers of cell viability, oxidative stress, inflammation, apoptosis, and signaling pathways were assessed.
Main Results:
- Rhein enhanced Müller cell viability and reduced oxidative stress markers (ROS, MDA) while increasing antioxidant enzymes (SOD, CAT).
- Rhein decreased pro-inflammatory cytokines (VEGF, IL-1β, IL-6, TNF-α) and attenuated apoptosis by modulating Bcl-2, Bax, and caspase-3.
- Rhein upregulated p-AMPK and PGC-1α, and these effects were reversed by the Sirt1 inhibitor EX-527.
Conclusions:
- Rhein exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties in high glucose-induced Müller cells.
- These protective effects are mediated through the activation of the AMPK/Sirt1/PGC-1α signaling pathway.
- Rhein demonstrates potential as a therapeutic agent for diabetic retinopathy by protecting against Müller cell dysfunction.
