β-amyloid peptide (Aβ) has been considered a critical factor that is associated with the development of oxidative stress and neuroinflammation in the pathogenesis of Alzheimer's disease. This study was performed to evaluate the effect of geraniin on Aβ25–35-caused oxidative damage and neuroinflammatory response, and its underlying mechanism. Geraniin protected pheochromocytoma12 (PC12) cells from Aβ25–35-mediated cell death by reducing oxidative stress and restoring cell cycle dysregulation. Moreover, geraniin markedly attenuated Aβ-triggered DNA injury that was partially associated with decreases in caspase-3 activity. Moreover, the compound significantly downregulated the release of neuroinflammatory factors. Upregulation of nuclear factor-κB activity was suppressed by geraniin, which was due to suppression of JNK, ERK1/2, and the p38 mitogen-activated protein kinase (MAPK) pathway. This was the first study to support further understanding of geraniin as a promising agent against neurotoxicity in the reduction of oxidative stress and neuroinflammation.
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