Ginkgolide B protects retinal pigment epithelial cells from H2O2-induced oxidative stress and apoptosis by activating the AMPK/Nrf2 pathway

Objective To investigate whether Ginkgolide B (GB) protects retinal pigment epithelial cells (RPEs) from hydrogen peroxide (H 2 O 2 )-induced oxidative stress and apoptosis, and to explore the potential involvement of the adenosine monophosphate-activated protein kinase α (AMPKα)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Methods Human RPEs were divided into the following groups: control, model (200 μmol/L H₂O₂ for 24 h), GB + H₂O₂, GB + H₂O₂ + Compound C (an AMPK inhibitor), H₂O₂ + Compound C, and GB alone. Cell viability, apoptosis, antioxidant parameters, and AMPKα/Nrf2 expression were assessed using the Cell Counting Kit-8 (CCK-8) assay, flow cytometry, colorimetric biochemical assays, transmission electron microscopy (TEM), quantitative polymerase chain reaction (PCR), and Western blot. Results TEM showed that GB attenuated H₂O₂-induced mitochondrial swelling and cristae disruption, which were reversed by Compound C. Compared with the model group, the GB + H₂O₂ group exhibited increased cell viability, decreased apoptosis, elevated activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as increased glutathione (GSH) content, and reduced malondialdehyde (MDA) (all p < 0.05), though protein carbonyl (PC) levels showed no significant amelioration. All protective effects were attenuated by Compound C. In the GB-alone group, the percentage of apoptotic cells, Nrf2 mRNA expression, and all other parameters did not differ significantly from those in the control group. Conclusion GB was associated with protection of RPEs against H₂O₂-induced oxidative stress and apoptosis. Because these protective effects were attenuated by pharmacological inhibition of AMPK, the findings suggest that AMPK/Nrf2 signaling may contribute to the cytoprotective actions of GB. However, additional mechanistic studies are required to confirm the involvement of this pathway.