Protective effect of Auraptene, a novel acetylcholinesterase inhibitor, on hydrogen peroxide-induced cell toxicity in PC12 cells.

Toxicol Res (Camb)

Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Khorasan Razavi, Mashhad, Azadi Square, 9177948954, Iran.

Published: December 2024

AI Article Synopsis

  • Alzheimer's disease (AD) is a progressive brain disorder characterized by memory loss and cognitive decline, largely linked to oxidative stress and cholinergic neuron dysfunction.
  • The study investigated auraptene, a novel acetylcholinesterase (AChE) inhibitor, for its protective effects against hydrogen peroxide (H2O2) induced cell death in PC12 cells, using several experimental techniques to assess cell health and apoptotic processes.
  • Results showed that auraptene significantly increased cell viability and reduced harmful reactive oxygen species, AChE activity, and cell apoptosis, suggesting it may help prevent nerve cell death by inhibiting AChE and blocking apoptotic pathways.

Article Abstract

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 (HO)-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: HO (150 μM) resulted in the cell death and apoptosis while, pretreatment with auraptene (10, 20 and 50 μM) significantly increased the viability ( < 0.01), and at 5-50 μM decreased ROS amount ( < 0.05 and  < 0.001). Pretreatment with auraptene (10, 20 and 50 μM) lessened AChE activity ( < 0.001), and at 20 and 50 μM reduced the release of LDH ( < 0.001), and at (10, 20 and 50 μM) diminished the percentage of apoptotic cells ( < 0.001). Also, pretreatment with auraptene at 10,20 and 50 μM prevented from poly (ADP-ribose) polymerase (PARP) cleavage ( < 0.001), and cytochrome c release ( < 0.01 and  < 0.001). The amount of caspase 3 activity ( < 0.001) and survivin ( < 0.001) were elevated after pretreatment of cells with auraptene at 10-50 μM and 10 and 50 μM.

Conclusion: It seems that auraptene has the ability to slow down or stop HO-induced nerve cells death by reducing the activity of AChE and suppression of internal pathway of apoptosis.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655956PMC
http://dx.doi.org/10.1093/toxres/tfae217DOI Listing

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