RRC ID |
59592
|
Author |
Shanmuganathan B, Sathya S, Balasubramaniam B, Balamurugan K, Devi KP.
|
Title |
Amyloid-β induced neuropathological actions are suppressed by Padina gymnospora (Phaeophyceae) and its active constituent α-bisabolol in Neuro2a cells and transgenic Caenorhabditis elegans Alzheimer's model.
|
Journal |
Nitric Oxide
|
Abstract |
The inhibition of Aβ peptide development and aggregation is a hopeful curative approach for the discovery of disease modifying drugs for Alzheimer's disease (AD) treatment. Recent research mainly focuses on the discovery of drugs from marine setting due to their immense therapeutic potential. The present study aims to evaluate the brown macroalga Padina gymnospora and its active constituent α-bisabolol against Aβ25-35 induced neurotoxicity in Neuro2a cells and transgenic Caenorhabditis elegans (CL2006 and CL4176). The results of the in vitro study revealed that the acetone extract of P. gymnospora (ACTPG) and its active constituent α-bisabolol restores the Aβ25-35 induced alteration in the oxidation of intracellular protein and lipids. In addition, ACTPG and α-bisabolol inhibited cholinesterase and β-secretase activity in Neuro2a cells. Moreover, the intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS) production was reduced by ACTPG and α-bisabolol in Neuro2a cells. The decrease in the expression level of apoptotic proteins such as Bax and caspase-3 in ACTPG and α-bisabolol treated group indicates that the seaweed and its bioactive compound have anti-apoptotic property. Further, the in vivo study revealed that the ACTPG and α-bisabolol exerts neuroprotective effect against Aβ induced proteotoxicity in transgenic C. elegans strains of AD. Moreover it altered the Aβ mediated pathways, lifespan, macromolecular damage and down regulated the AD related gene expression of ace-1, hsp-4 and Aβ, thereby preventing Aβ synthesis. Overall, the outcome of the study signifies the neuroprotective effect of ACTPG and α-bisabolol against Aβ mediated AD pathology.
|
Volume |
91
|
Pages |
52-66
|
Published |
2019-10-1
|
DOI |
10.1016/j.niox.2019.07.009
|
PII |
S1089-8603(19)30070-9
|
PMID |
31362072
|
MeSH |
Alzheimer Disease / chemically induced
Alzheimer Disease / drug therapy*
Amyloid beta-Peptides / genetics
Amyloid beta-Peptides / metabolism*
Animals
Animals, Genetically Modified
Apoptosis / drug effects
Biological Products / pharmacology*
Caenorhabditis elegans / genetics
Cell Line, Tumor
Enzyme Inhibitors / pharmacology
Humans
Membrane Potential, Mitochondrial / drug effects
Mice
Monocyclic Sesquiterpenes / pharmacology*
Neuroprotective Agents / pharmacology*
Oxidative Stress / drug effects
Peptide Fragments / genetics
Peptide Fragments / metabolism*
Phaeophyta / chemistry*
Reactive Nitrogen Species / metabolism
Reactive Oxygen Species / metabolism
|
IF |
3.371
|
Times Cited |
10
|
Resource |
C.elegans |
|