Ginkgolide B-induced AMPK pathway activation protects astrocytes by regulating endoplasmic reticulum stress, oxidative stress and energy metabolism induced by Aβ(1-42)

Ginkgolide B (GB), the diterpenoid lactone compound isolated from the extracts of Ginkgo biloba leaves, significantly improves cognitive impairment, but its potential pharmacological effect on astrocytes induced by β-amyloid (Aβ)(1-42) remains to be elucidated. The present study aimed to investigate the protective effect and mechanism of GB on astrocytes with Aβ(1-42)-induced apoptosis in Alzheimer's disease (AD). Astrocytes obtained from Sprague Dawley rats were randomly divided into control, Aβ, GB and GB + compound C groups. Cell viability and apoptosis were analyzed using Cell Counting Kit-8 and flow cytometry assays, respectively. Protein and mRNA expression levels were analyzed using western blotting and reverse transcription-quantitative PCR, respectively. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), reactive oxygen species (ROS) and ATP were determined using the corresponding commercial kits. The findings revealed that GB attenuated Aβ(1-42)-induced apoptosis and the 5′ adenosine monophosphate- activated protein kinase (AMPK) inhibitor compound C reversed the protective effects of GB. In addition, GB reversed Aβ(1-42)-induced oxidative damage and energy metabolism disorders, including decreases in the levels of SOD, GSH-Px and ATP and increased the levels of MDA and ROS in astrocytes, while compound C reversed the anti-oxidative effect and the involvement of GB in maintaining energy metabolism in astrocytes. Finally, GB decreased the expression levels of the endoplasmic reticulum stress (ERS) proteins and the apoptotic protein CHOP and increased both mRNA and protein expression of the components of the energy metabolism-related AMPK/peroxisome proliferator-activated receptor γ coactivator 1α/peroxisome proliferator-activated receptor α and anti-oxidation-related nuclear respiratory factor 2/heme oxygenase 1/NAD(P)H dehydrogenase (quinone 1) pathways and downregulated the expression of β-secretase 1. However, compound C could antagonize these effects. In conclusion, the findings demonstrated that GB protected against Aβ(1-42)-induced apoptosis by inhibiting ERS, oxidative stress, energy metabolism disorders and Aβ(1-42) production probably by activating AMPK signaling pathways. The findings provided an innovative insight into the treatment using GB as a therapeutic in Aβ(1-42)-related AD.