PUBLICATION

Amelioration of cognitive deficit in zebrafish by an undescribed anthraquinone from Juglans regia L.: An in-silico, in-vitro and in-vivo approach

Authors
Devidas, S.B., Rahmatkar, S.N., Singh, R., Sendri, N., Purohit, R., Singh, D., Bhandari, P.
ID
ZDB-PUB-210608-4
Date
2021
Source
European Journal of Pharmacology   906: 174234 (Journal)
Registered Authors
Keywords
Acetylcholinesterase, Anthraquinone, Juglans regia L, Neurotoxicity, T-maze, Zebrafish
MeSH Terms
  • Acetylcholinesterase/metabolism
  • Acrylamide/administration & dosage
  • Acrylamide/toxicity
  • Animals
  • Anthraquinones/isolation & purification
  • Anthraquinones/pharmacology*
  • Anthraquinones/therapeutic use
  • Cholinesterase Inhibitors/isolation & purification
  • Cholinesterase Inhibitors/pharmacology*
  • Cholinesterase Inhibitors/therapeutic use
  • Cognitive Dysfunction/chemically induced
  • Cognitive Dysfunction/prevention & control*
  • Disease Models, Animal
  • Humans
  • Juglans/chemistry
  • Learning/drug effects
  • Memory/drug effects
  • Molecular Docking Simulation
  • Neuroprotective Agents/isolation & purification
  • Neuroprotective Agents/pharmacology*
  • Neuroprotective Agents/therapeutic use
  • Zebrafish
PubMed
34090895 Full text @ Eur. J. Pharmacol.
Abstract
An undescribed anthraquinone assigned as 1-Hydroxy-5,5-dimethyl-5,6,7,8-tetrahydro-9,10-anthraquinone (compound 1) was isolated from ethylacetate extract of Juglans regia. The structure of the compound was established on the basis of 1D, 2D NMR (HSQC, HMBC, COSY), ESI-QTOF-MS/MS spectroscopy. The molecular docking studies of compound 1 indicated similar molecular interactions as that of co-crystalized inhibitor. Compound 1 showed hydrogen bonds with residues PHE295, GLY121, π-σ interactions with TYR 341, π-π interactions with HIS 447 residues, and π-alkyl with TRP86 and TYR 337. On the basis of in-silico interaction studies of compound 1 with proteins, it was tested using acetylcholinesterase inhibition assay, acrylamide-induced neurotoxicity test of zebrafish larva, and scopolamine-induced cognitive deficit model of adult zebrafish. The compound 1 showed potent acetylcholinesterase inhibition activity, prevented acrylamide-induced neurotoxicity and improved learning and memory functions in T-maze test. The results established compound 1 to be a potential neuroprotective natural product for amelioration of cognitive impairment.
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