Alzheimer’s disease (AD) is a destructive neurodegenerative disease that currently has no effective treatment option available. Ginkgolide B (GB) is a terpene lactone derivative of Ginkgo biloba that possesses neuroprotective effects in various diseases. The aim of the present study was to investigate whether GB protects against cognitive impairment in AD by mitigating oxidative stress, inflammation and ferroptosis using senescence-accelerated P8 (SAMP8) mice. The results showed that GB improved the cognitive dysfunction of SAMP8 mice in the Morris water maze and novel object recognition test, which was associated with the attenuation of oxidative stress, inflammation and nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4 (GPX4) pathway-mediated ferroptosis. Furthermore, Ras-selective lethal small molecule 3, a GPX4 inhibitor and ferroptosis inducer, compromised GB-induced cognitive performance in SAMP8 mice. These findings suggested that GB alleviated AD-induced cognitive defects by mitigating oxidative stress, neuroinflammation and ferroptosis, and that the inhibition of ferroptosis is required for GB to have beneficial effects in AD.
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