Neuroprotective effects of acetophenone dimers from Acronychia pedunculata on human neuroblastoma SH-SY5Y cells in glutamate-induced apoptosis

Abstract

Excessive glutamate in the central nervous system is a key pathogenic mechanism in neurodegenerative disorder. This study investigated the neuroprotective effect of acrovestone (AVT), an acetophenone dimer from Acronychia pedunculata, and its underlying mechanism in glutamate-induced neuroblastoma SH-SY5Y cells. The protective effect of AVT was evaluted through cell viability assay and analysis of apoptosis-related protein expression via Western blot analysis. Our finding revealed that AVT significantly improved cell viability under glutamate induced excitotoxicity conditions. Mechanistic investigations demonstrated that AVT attenuated the activation of pro-apoptotic proteins including ERK1/2, Bim, BAX, caspase-3, caspase-7, and caspase-9. Concurrently, AVT upregulated the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. Furthermore, AVT modulated the Akt/FoxO3a signaling pathway, alleviating acute oxidative stress caused by glutamate exposure in SH-SY5Y cells. These results suggest that AVT inhibits glutamate-induced neurotoxicity by modulating apoptosis signaling pathway, highlighting its potential as a therapeutic candidate for preventing neurodegenerative diseases.

Graphical abstract