Neuroprotective and Neurodifferentiative Properties of Ferulic Acid

Background and Aim: Ferulic acid (FA) is a phenolic compound withknown anti-apoptotic and anti-oxidative properties. Effect of FA on theinduction of neurogenesis and neuro-differentiation beside its effect onneuroprotection makes this compound very interesting for stem cellresearches. We designed this set of experiments to evaluate the effect ofFA on neuronal differentiation and neuroprotection.Methods: ROS-mediated apoptosis was induced on PC12 cells by usinghydrogen peroxide then with the treatment of different concentrationsof FA was started. To evaluate the differentiation-inducing the effect ofFA, PC12 cells and mouse neural stem cells (mNSCs) were treated withdifferent concentrations of FA. MTT, quantitative real-time RT-PCR andimmunostaining assays were performed on cells.Results: FA treatment at low concentrations significantly reduced theapoptosis rate in treated PC12 cells. Real-time RT-PCR and western blotassays confirmed that FA revealed this effect through stabilization anddegradation of P53 by increasing the expression rate of SIRT1, SIRT7and MDM2 and down-regulation of USP7. Beside this anti-apoptoticeffect, FA treatments on PC12 cells and mNSCs at higher concentrationson PC12 cells and mNSCs increased their differentiation toward matureneurons. Immunocytochemical staining against beta-tubulin III andMap2 verified the presence of mature neurons, and western blot assay onFA treated PC12 cells showed a stepwise rise of phosphorylated-ERK1/2 as the concentration of FA was increased.Conclusion: our findings showed that FA at low concentrations has aneuroprotective effect through up-regulation of SIRT1, SIRT7, andMDM2, and in higher concentrations can promote neural differentiationand neurite outgrowth.

کلیدواژه ها:

Ferulic Acid ، PC12 Cells ، Apoptosis ، Survival ، Neuronal differentiation