Hadipour_2024_Toxicol.Res.(Camb)_13_tfae217

OBJECTIVE: Alzheimer's disease (ad) is a progressive and degenerative disorder of the central nervous system that is associated with cognitive and memory impairment. The main factors which have been implicated in neurodegeneration of ad are oxidative stress and cholinergic neurons dysfunction. Here, we examined the effects of auraptene, a novel acetylcholinesterase (AChE) inhibitor, on hydrogen peroxide (H(2)O(2))-induced cell death in PC12 cells. METHODS: Thereby, we measured cell viability, intracellular reactive oxygen species (ROS) production, AChE inhibitory activity, cell damage and apoptosis with AlmarBlue, 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA), Ellman method, lactate dehydrogenase (LDH) release, propidium iodide (PI) staining and western blot analysis, respectively. RESULTS: H(2)O(2) (150 microM) resulted in the cell death and apoptosis while, pretreatment with auraptene (10, 20 and 50 microM) significantly increased the viability (P < 0.01), and at 5-50 microM decreased ROS amount (P < 0.05 and P < 0.001). Pretreatment with auraptene (10, 20 and 50 microM) lessened AChE activity (P < 0.001), and at 20 and 50 microM reduced the release of LDH (P < 0.001), and at (10, 20 and 50 microM) diminished the percentage of apoptotic cells (P < 0.001). Also, pretreatment with auraptene at 10,20 and 50 microM prevented from poly (ADP-ribose) polymerase (PARP) cleavage (P < 0.001), and cytochrome c release (P < 0.01 and P < 0.001). The amount of caspase 3 activity (P < 0.001) and survivin (P < 0.001) were elevated after pretreatment of cells with auraptene at 10-50 microM and 10 and 50 microM. CONCLUSION: It seems that auraptene has the ability to slow down or stop H(2)O(2)-induced nerve cells death by reducing the activity of AChE and suppression of internal pathway of apoptosis.