F Homayouni Moghadam - Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
M Khajeh-Mobarakeh - Department of Biology, ACECR Institute of Higher Education, Is-fahan, Iran
R Dehghani Varnamkhasti - Department of Biology, ACECR Institute of Higher Education, Is-fahan, Iran
M Mesbah-Ardakani - Imam Hossein Hospital of Sepidan, Shiraz University of Medical Sciences, Shiraz, Iran
MH Nasr-Esfahani - Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

Objective: Ferulic acid (FA) as a phenolic phytochemical has many medicinal properties that have been proven to have anti-oxidant and protective effects on various cell types, including neurons. However, studies on its effects on other biological pro-cesses, such as inducing neuronal differentiation and the stimu-latory effect on the change of microglia phenotype from M۱ to M۲, are very limited.Materials and Methods: In a series of studies on PC۱۲ cells, neuronal precursors, and microglia cells, we found that these neurons reacted differently to different concentrations of the compound. In these experiments, we treated PC۱۲, NSC and microglia cells with different concentrations of FA and evalu-ated the expression of genes and proteins involved in differentiation, survival and inflammation in different laboratory conditions. Western blotting, quantitative real-time PCR, im-muno-cytochemical staining, survival measurement with MTT assay and morphological studies were used to confirm the find-ings.Results: FA specifically promotes the survival of nerve cells and increases their resistance to oxidative stress by stimulating the expression of Sirtuins, especially SIRT ۱ and ۷. It also in-duces differentiation in NSCs toward neurons through the ERK ۱/۲ signaling pathway. Regarding induction of differentiation, our studies showed that at high concentrations FA shows this property, while at low concentrations it promotes neuroprotec-tion. Regarding the stimulation of microglia, our study showed that FA in low concentrations has the property of inducing the M۱ to M۲ shift of microglia and thereby reducing the aggres-sive properties of microglia. In this way, FA acts through sup-pression of M۱-inflammatory genes (IL ۱β, IL۶, TNFα, OPG) and increasing the expression of M۲-anti-inflammatory mark-ers (IL۱۰, IL۴, TGFβ).Conclusion: Our studies show that FA is not just an antioxidant and can have significant effects on inducing differentiation and reducing inflammation in the nervous system.

Ferulic acid, Neuron, Microglia, Differentiation, Pro-tection