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Neuroprotection against Aluminum Chloride-Induced Hippocampus Damage in Albino Wistar Rats by Leucophyllum frutescens (Berl.) I.M. Johnst. Leaf Extracts: A Detailed Insight into Phytochemical Analysis and Antioxidant and Enzyme Inhibition Assays

Authors :
Imtiaz Ahmad
Saeed Ahmad
Esra Küpeli Akkol
Huma Rao
Muhammad Nadeem Shahzad
Mehwish Nawaz
Bilal Ahmad Ghalloo
Wayne Thomas Shier
Eduardo Sobarzo-Sánchez
Source :
Frontiers in Bioscience-Landmark, Vol 28, Iss 8, p 184 (2023)
Publication Year :
2023
Publisher :
IMR Press, 2023.

Abstract

Background: A previously unstudied medicinal plant, Leucophyllum frutescens (Berland.) I.M. Johnst. (Scrophulariaceae) was investigated to evaluate its potential in preventing and treating neurodegenerative diseases, including Alzheimer’s disease. Methods: Methanolic leaf extract (MELE) and its fractions (HELE, CHLE, and BULE) were evaluated for their polyphenolic content and antioxidant activity by five different methods, including in vitro enzyme inhibition assays, which are clinically linked to neurodegenerative diseases. The potentially active n-butanol fraction (BULE) was further evaluated for its neuroprotective effects using an albino rat animal model and phytoconstituents profiling using Liquid chromatography with tandem mass spectrometry (LC–MS/MS), and in silico molecular docking by Maestro® Schrödinger. Results: The n-butanol fraction (BULE) in the hydroalcoholic leaf extract exhibited the highest total phenolic content (230.435 ± 1.575 mg gallic acid equivalent gm-1± SD). The chloroform leaf extract exhibited the highest total flavonoid content (293.343 ± 3.756 mg quercetin equivalent gm-1± SD) as well as the highest antioxidant content, which was equivalent to Trolox, with five assay methods. Similarly, the chloroform and n-butanol fractions from the hydroalcoholic leaf extract significantly inhibited human acetylcholinesterase and butyrylcholinesterase with their IC50 values of 12.14 ± 0.85 and 129.73 ± 1.14 µg∙mL-1, respectively. The in vivo study revealed that BULE exhibited a significant neuroprotective effect at doses of 200 and 400 mg/kg/day in an aluminum chloride-induced neurodegenerative albino rat model. The LC–MS/MS analysis of BULE tentatively confirmed the presence of biologically active secondary metabolites, such as theobromine, propyl gallate, quercetin-3-O-glucoside, myricetin-3-acetylrhamnoside, isoquercitrin-6′-O-malonate, diosmetin-7-O-glucuronide-3′-O-pentose, pinoresinol diglucoside, asarinin, eridictoyl, epigallocatechin, methyl gallate derivative, and eudesmin. The results from the computational molecular docking of the identified secondary metabolites revealed that diosmetin-7-O-glucuronide-3′-O-pentose had the highest binding affinity to human butyrylcholinesterase, while isoquercetin-6′-O-malonate had the highest to human acetylcholinesterase, and pinoresinol diglucoside to human salivary alpha-amylase. Conclusions: The present study concluded a need for further exploration into this medicinal plant, including the isolation of the bioactive compounds responsible for its neuroprotective effects.

Details

Language :
English
ISSN :
27686701
Volume :
28
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Frontiers in Bioscience-Landmark
Publication Type :
Academic Journal
Accession number :
edsdoj.6d90fae2cefb4701bab56922af48da32
Document Type :
article
Full Text :
https://doi.org/10.31083/j.fbl2808184