Vitexin inhibits Aβ25-35 induced toxicity in Neuro-2a cells by augmenting Nrf-2/HO-1 dependent antioxidant pathway and regulating lipid homeostasis by the activation of LXR-α.
Amyloid beta (Aβ) formation is one of the neuropathological hallmarks of Alzheimer's disease (AD), which induces the generation of reactive oxygen species (ROS), further leading to the alteration of several signalling pathways. In the present study, vitexin has been evaluated for its neuroprotective activity against Aβ25-35 induced toxicity in Neuro-2a cells. Results of cell free studies indicated that vitexin significantly inhibited the aggregation of Aβ25-35. Studies in Neuro-2a cells revealed that Aβ25-35 significantly affected the cell viability by inducing ROS mediated toxicity and apoptosis. However, pre-treatment of Neuro-2a cells with vitexin (50 μM) significantly restored the cell viability up to 92.86 ± 5.57%. Vitexin has been found to inhibit the production of free radicals and suppress ROS mediated lipid peroxidation, protein oxidation and loss of membrane potential. Also, vitexin modulated the expression of genes involved in antioxidant response mechanisms (Nrf-2, HO-1), cholesterol metabolism (LXR-α, APOE, ABCA-1, Seladin-1), and endoplasmic reticulum stress (Grp78, Gadd153) to offer neuroprotection. Aβ25-35 induced caspase-3 activation, and Bax protein expression was also found to be significantly inhibited by vitexin. Taken together, our results indicate that vitexin offers neuroprotection to cells in part via augmenting the antioxidant mechanisms, maintaining lipid homeostasis and inhibiting apoptosis induced by Aβ.
['Malar|Dicson Sheeja|DS|', 'Suryanarayanan|Venkatesan|V|', 'Prasanth|Mani Iyer|MI|', 'Singh|Sanjeev Kumar|SK|', 'Balamurugan|Krishnaswamy|K|', 'Devi|Kasi Pandima|KP|']
D016229:Amyloid beta-Peptides D000818:Animals D047310:Apigenin D053148:Caspase 3 D045744:Cell Line, Tumor D002470:Cell Survival D000091342:Endoplasmic Reticulum Chaperone BiP D005978:Glutathione D006360:Heat-Shock Proteins D051547:Heme Oxygenase-1 D000071518:Liver X Receptors D053078:Membrane Potential, Mitochondrial D008565:Membrane Proteins D051379:Mice D051267:NF-E2-Related Factor 2 D018696:Neuroprotective Agents D010446:Peptide Fragments D026361:Reactive Nitrogen Species D017382:Reactive Oxygen Species D015398:Signal Transduction D051742:Transcription Factor CHOP
Vitexin Aggregation Lipid peroxidation Seladin-1 Caspase-3