Alzheimer's disease (AD) is the most common type of dementia with a complex pathobiology. The clinically approved treatments against AD attempt to provide only symptomatic relief. Therefore, the curre Show more
Alzheimer's disease (AD) is the most common type of dementia with a complex pathobiology. The clinically approved treatments against AD attempt to provide only symptomatic relief. Therefore, the current findings highlighted the neuroprotective effect and the potential signaling mechanism of quinic acid (1) and its amide derivatives (2-4) against phytohaemagglutinin (PHA)-induced neurotoxicity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was conducted to assess the proliferative potential of 1-4 which were observed to increase the viability of SH-SY5Y cells. Microscopic examination of the cells induced with PHA and post treated with the respective test compound showed that 1 as well as its derivatives (2-4) improved morphology of the cells and subside the toxic effects of PHA. Evaluation of reactive oxygen species (ROS) production demonstrated that the test compounds except 4 decreased PHA-induced ROS in SH-SY5Y cells. The mRNA expression analysis of IL-1β, TNF-α, p38-α, p38-β and the disease associated ADAM10 and BACE1 genes revealed that 1 and its derivatives (2-4) reduced the PHA-induced elevated levels of inflammatory molecules whereas the compounds did not positively modulate the expression of proteolytic secretases. Moreover, the compounds reduced the disease specific increased expression of amyloid beta (Aβ), phosphorylated tau and activated p38 MAPK observed through fluorescence microscopy. Show less