Improving the inhibition of β-amyloid aggregation by withanolide and withanoside derivatives

2021-03-01

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Rajagopal Subramanyam *

DOI：10.1016/j.ijbiomac.2021.01.094

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Here, we have studied the ameliorative effects of Withania somnifera derivatives (Withanolide A, Withanolide B, Withanoside IV, andWithanoside V) on the fibril formation of amyloid-beta (42) for Alzheimer's disease. We analyzed reduction in the aggregation of beta amyloid protein with these Ashwagandha derivatives by Thioflavin T assay in the oligomeric and fibrillar state. We have tested the cytotoxic activity of these compounds against human SK-N-SH cell line for 48 h, and the IC (50) value found to be 28.61 +/- 2.91, 14.84 +/- 1.45, 18.76 +/- 0.76 and 30.14 +/- 2.59 mu M, respectively. After the treatment of the cells with half the concentration of IC (50) value, there was a remarkable decrease in the number of apoptotic cells stained by TUNEL assay indicating the DNA damage and also observed significant decrease of reactive oxygen species. Also, the binding and molecular stability of these derivatives with amyloid beta was also studied using bioinformatics tools where these molecules were interacted at LVFFA region which is inhibition site of amyloid-beta 1 (42). These studies revealed that the Withanolides and Withanosides interact with the hydrophobic core of amyloid-beta (1-42) in the oligomeric stage, preventing further interaction with the monomers and diminishing aggregation. (C) 2021 Elsevier B.V. All rights reserved.

Keywords:

Amyloid beta(1-42)

Withania somnifera

Thioflavin-T fluorescence assay

Cell viability assay

Molecular docking

Molecular dynamics

Improving the inhibition of β-amyloid aggregation by withanolide and withanoside derivatives

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