1. Amelioration of cognitive deficit in zebrafish by an undescribed anthraquinone from Juglans regia L.: An in-silico, in-vitro and in-vivo approach
- Author
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Rahul Singh, Damanpreet Singh, Shinde Bhagatsing Devidas, Pamita Bhandari, Nitisha Sendri, Shubham Nilkanth Rahmatkar, and Rituraj Purohit
- Subjects
0301 basic medicine ,In silico ,Anthraquinones ,Juglans ,Anthraquinone ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Memory ,In vivo ,medicine ,Animals ,Humans ,Learning ,Cognitive Dysfunction ,Zebrafish ,Pharmacology ,Acrylamide ,Natural product ,biology ,Neurotoxicity ,biology.organism_classification ,medicine.disease ,Acetylcholinesterase ,In vitro ,Molecular Docking Simulation ,Disease Models, Animal ,Neuroprotective Agents ,030104 developmental biology ,chemistry ,Biochemistry ,Cholinesterase Inhibitors ,030217 neurology & neurosurgery - 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 L. 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.
- Published
- 2021