Protein Kinase C Involvement in Neuroprotective Effects of Thymol and Carvacrol Against Toxicity Induced by Amyloid-Β in Rat Hippocampal Neurons

Abstract

Introduction: We have reported that thymol and carvacrol can improve cognitive abilities in Alzheimer’s disease (AD) rat model. However, the mechanism of their action is not yet fully understood. Recently, our in vitro results suggested that PC12 cell death-induced by Aβ25-35 can be protected by thymol and carvacrol via PKC and ROS pathways. So, we hypothesize that the mechanisms of thymol and carvacrol in improving the learning impairment in AD rat model may be related to their effects on PKC. So, the activity of PKC and protein expression levels of PKCα was examined in the hippocampal cells of AD rat model. Methods: To examine thymol and carvacrol effects, we performed behavioral test in AD rat model induced by Aβ25–35 neurotoxicity. To access the underlying mechanism of protective effects, western blotting was performed with antibodies against PKCα. We also measured PKC activity assay by Elisa. Histopathological studies were carried out in hippocampus by hematoxylin & eosin (H&E). Results: It was shown that escape latency increased in Aβ-received rats compared to control group and thymol and carvacrol reversed this deficit. Furthermore, these compouds could enhance PKC activity, and increase the PKCα expression ratio. Moreover, H&E showed that Aβ caused shrinkage of the CA1 pyramidal neurons. However, thymol and carvacrol treatments could prevent this effect of Aβ peptides. Conclusions: This study suggests that Aβ results in memory decline and histochemical disturbances in hippocampus. Moreover, these results revealed that thymol and carvacrol could have protective effects on cognition in AD-like models via PKC activation.