Research Article: Ginkgolide B protects retinal pigment epithelial cells from H 2 O 2 -induced oxidative stress and apoptosis by activating the AMPK/Nrf2 pathway
Abstract:
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 ? (AMPK?)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.
Human RPEs were divided into the following groups: control, model (200??mol/L H?O? for 24?h), GB?+?H?O?, GB?+?H?O??+?Compound C (an AMPK inhibitor), H?O??+?Compound C, and GB alone. Cell viability, apoptosis, antioxidant parameters, and AMPK?/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.
TEM showed that GB attenuated H?O?-induced mitochondrial swelling and cristae disruption, which were reversed by Compound C. Compared with the model group, the GB?+?H?O? 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.
GB was associated with protection of RPEs against H?O?-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.
Introduction:
Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly worldwide. Recent epidemiological analysis in the United States indicates that the crude prevalence of early AMD in people aged 40 and older reached 11.64% in 2020, with late AMD at approximately 0.94%, showing significant variations by age, sex, and race ( 1 ). A study also suggests that the number of AMD patients will increase by about 50% around 2020 due to population aging, with over 7 million people at potential risk for…
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