Diosgenin protects retinal pigment epithelial cells from inflammatory damage and oxidative stress induced by high glucose by activating AMPK/Nrf2/HO‐1 pathway

INTRODUCTION: Diosgenin is a natural steroidal compound with reported antidiabetic and many other protective properties. This study aimed to explore the protective effect of diosgenin on high‐glucose (HG)‐induced retinal pigment epithelial cells. METHODS: HG‐induced ARPE‐19 cells were considered as a cell model of diabetic retinopathy (DR). The viability and apoptosis of ARPE‐19 cells induced by HG treated with either diosgenin or Compound C (CC; dorsomorphin) were detected by Cell Counting Kit‐8 assay and flow cytometric analysis. The expression of apoptosis‐related proteins, inflammation‐related proteins, and AMPK/Nrf2/HO‐1 pathway‐related proteins was detected by western blotting. The levels of inflammatory cytokines and detection of oxidative stress indexes were performed using the appropriate assay kits. The messenger RNA expression of inflammatory cytokines was detected by real‐time quantitative polymerase chain reaction. RESULTS: There was no obvious effect of diosgenin on the viability of ARPE‐19 cells and the viability of ARPE‐19 cells was significantly reduced after HG induction. However, diosgenin increased the viability, inhibited the apoptosis, and reduced the inflammatory response and oxidative stress of ARPE‐19 cells induced by HG. In addition, diosgenin could activate the AMPK/Nrf2/HO‐1 pathway. CC, an AMPK inhibitor, could reverse the above changes caused by diosgenin treatment in ARPE‐19 cells induced by HG. CONCLUSIONS: Diosgenin could protect ARPE‐19 cells from inflammatory damage and oxidative stress induced by HG, by activating the AMPK/Nrf2/HO‐1 pathway.