Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 173, Issue -, Pages 56-65Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2021.01.094
Keywords
Amyloid beta(1-42); Withania somnifera; Thioflavin-T fluorescence assay; Cell viability assay; Molecular docking; Molecular dynamics
Funding
- Science and Engineering Research Board, India [SB/EMEQ-064/2014]
- CSIR
Ask authors/readers for more resources
Studies have shown that Withania somnifera derivatives have ameliorative effects on the fibril formation of amyloid-beta (42) for Alzheimer's disease, reducing aggregation and cytotoxicity. These derivatives interact with the hydrophobic core of amyloid-beta at the inhibition site, preventing further aggregation and cell apoptosis.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available