Title:In silico Evaluation and Neuroprotective Effect of Jasmonic Acid on Sleep
Deprivation Induced Alzheimer’s in Zebrafish
Volume: 19
Issue: 7
Author(s): Tamilanban Thamaraikani*, Vijay Babu Anandan, Manasa Karnam, Manimaran Vasanthan and Gayathiri Kichenamurthy
Affiliation:
- Department of Pharmacology, SRM College of Pharmacy, SRMIST, Kattankulathur, 603203, Tamilnadu, India
Keywords:
Jasmonic acid, autodock, zebrafish, T-maze, Y-maze, sleep deprivation.
Abstract:
Background: Disturbances in the sleep cycle have been often associated with the depletion
of oxidant enzymes and deposition of beta-amyloid plaques leading to neurodegeneration
in Alzheimer's disease (AD). Healthy sleep time and sleep cycles were proven to clear the betaamyloid
out of the brain and also promote the synthesis and functions of anti-oxidant enzymes.
Objective: Jasmonic acid was evaluated to enhance the cognition and acetylcholine enzyme in the
sleep deprivation-induced Alzheimer's by using the zebrafish model.
Methods: The molecular properties, bioactivity score, and pharmacokinetic parameters of
jasmonic acid were predicted using Molinspiration, SwissADME, and PreADMET tools.
Jasmonic acid obeys Lipinski's rule and has significant bioavailability and blood-brain barrier
penetration. The prediction of binding energy and interactions of jasmonic acid with six selected
receptors was performed using AutoDock 4.2 software. It has significant binding affinity and interactions
with different receptors which predict a multi-target potential using in-silico studies. In
vivo neurobehavioral analysis of jasmonic acid was performed with zebrafish by using T-maze,
Y-maze, and inhibitory avoidance apparatus and the results reveal Jasmonic acid produces more
memory retention in zebrafish. In vitro assays of jasmonic acid on acetylcholinesterase enzyme
level, glucose level, catalase activity, and lipid peroxidation activity were performed. Jasmonic
acid shows cholinesterase inhibition, it acts as a good anti-oxidant and increases glucose metabolism
on zebra fish brain homogenate using various assays. Jasmonic acid decreases neurodegeneration,
and amyloid deposits in zebrafish brains using histopathological studies.
Results: In silico molecular docking studies, in vitro assays, in vivo neurobehavioral analysis and
histopathological studies reveal that jasmonic acid showed significant activity against sleep deprivation-
induced AD in the zebrafish model.
Conclusion: Hence, jasmonic acid will be carried out for further preclinical and clinical studies in
order to prove the same for the management of Alzheimer's disease.