Quercetin alleviates 6-OHDA-caused apoptosis in SH-SY5Y cells.

ABSTRACT

Aim: This study is primarily designed to investigate the potential neuroprotective effects of polyphenol against 6-OHDAcaused neurotoxicity on SH-SY5Y cells. Materials and Methods: Cytotoxic effect of 6-OHDA and valuable role of quercetin, myricetin and kaempferol on SH-SY5Y cells were analyzed by MTT assay. Generation of 6-OHDA-stimulated reactive oxygen species (ROS) was measured using DCFDA fluorescence dye. Alteration of 6-OHDA-caused mitochondrial membrane potential and nuclear condensation was investigated with the help of rhodamine-123 and hoechest stain. Immunoblotting was performed to detect the expression level of 6-OHDA-caused alpha-synuclein (á-syn), Bcl-2 associated protein X (BAX), caspase 3, cleaved Poly ADP - ribose polymerase (PARP) and Bcell lymphoma 2 proteins (Bcl-2). Result: Through MTT assay, quercetin was selected over myricetin and kaempferol to counter 6-OHDA-caused cell death. The research delves into unraveling the intricate mechanisms underlying 6-OHDA-induced neurotoxicity, encompassing alterations in cellular morphology, escalation of oxidative stress, perturbation in mitochondrial membrane potential, and nuclear condensation. Exposure to 6-OHDA is implicated in the upregulation of á-syn protein, contributing to the aggravation of neurotoxicity. Concurrently, 6-OHDA orchestrates the apoptotic pathway by upregulating the expression of proapoptotic proteins such as BAX, caspase 3, and PARP, while down regulating the expression of the Bcl-2, affirming its role in apoptosis induction. Quercetin demonstrated ability to attenuate the expression of á-syn in the presence of 6-OHDA-caused injury in SH-SY5Y cells. Conclusion: Taken together, these findings collectively underscore the therapeutic potential of quercetin as a promising agent against neurotoxicity caused by 6-OHDA.