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. 2020 Nov 15;10(11):1556.
doi: 10.3390/biom10111556.

Potential Nutraceutical Properties of Leaves from Several Commonly Cultivated Plants

Hafsa Amat-Ur-Rasool  1   2 , Fenella Symes  3 , David Tooth  4 , Larissa-Nele Schaffert  1 , Ekramy Elmorsy  1   5 , Mehboob Ahmed  2 , Shahida Hasnain  2 , Wayne G Carter  1
Affiliations

Potential Nutraceutical Properties of Leaves from Several Commonly Cultivated Plants

Hafsa Amat-Ur-Rasool et al. Biomolecules. .

Abstract

Chronic dietary ingestion of suitable phytochemicals may assist with limiting or negating neurodegenerative decline. Current therapeutics used to treat Alzheimer disease elicit broad adverse drug reactions, and alternative sources of cholinesterase inhibitors (ChEIs) are required. Herein, we screened methanolic extracts from seven commonly cultivated plants for their nutraceutical potential; ability to inhibit acetylcholinesterase (AChE) and butyryl-cholinesterase (BuChE), and provision of antioxidant activity through their 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging capabilities. Potential neurotoxicity of plant extracts was examined via application to SHSY-5Y neuroblastoma cells and quantitation of cell viability. Methanolic extracts of Citrus limon (Lemon), Bombax ceiba (Red silk-cotton), Lawsonia inermis (Henna), Eucalyptus globulus (Eucalyptus), Ocimum basilicum (Basil), Citrus reticulata (Mandarin orange), and Mentha spicata (Spearmint) all displayed concentration-dependent inhibition of AChE and BuChE. The majority of extracts inhibited AChE and BuChE to near equipotency, with Henna and Eucalyptus extracts the two most potent ChEIs. All plant extracts were able to scavenge free radicals in a concentration-dependent manner, with Eucalyptus the most potent antioxidant. Toxicity of plant extracts to neuronal cells was concentration dependent, with Eucalyptus also the most toxic extract. Fractionation of plant extracts and analysis by mass spectrometry identified a number of plant polyphenols that might have contributed to the cholinesterase inhibition: 3-caffeoylquinic acid, methyl 4-caffeoylquinate, kaempferol-acetyl-glycoside, quercetin 3-rutinoside, quercetin-acetyl-glycoside, kaempferol 3-O-glucoside, and quercetin 3-O-glucoside. In silico molecular modeling of these polyphenols demonstrated their improved AChE and BuChE binding affinities compared to the current FDA-approved dual ChEI, galantamine. Collectively, all the plant extracts contained nutraceutical agents as antioxidants and ChEIs and, therefore, their chronic consumption may prove beneficial to combat the pathological deficits that accrue in Alzheimer disease.

Keywords: Alzheimer disease; acetylcholinesterase inhibitors; antioxidants; butyrylcholinesterase inhibitors; molecular modelling; nutraceuticals; phytochemicals.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
The cholinergic system and cholinergic synapse. (a) Overview of the cholinergic system: DB, diagonal band of Broca; LDT, laterodorsal pontine tegmentum; MSN, medial septal nucleus; NB, nucleus basalis; PPT, pedunculopontine tegmental nucleus. (b) The cholinergic synapse: ACh, acetylcholine; AChE, acetylcholinesterase; BuChE, butyrylcholinesterase; ChAT, choline acetyltransferase; CHT1, choline transporter; VAChT, vesicular acetylcholine transporter.
Figure 2
Figure 2
Assessment of the ability of plant extracts and galantamine to inhibit AChE and BuChE. (a) Inhibition of AChE by plant extracts. (b) Inhibition of BuChE by plant extracts. (c) Inhibition of AChE and BuChE by galantamine. Assays were performed using modified Ellman’s assay [40]. Results are expressed as means ± SEM, for an n-number of 4.
Figure 3
Figure 3
Comparison of BuChE and AChE inhibitory activity for plant extracts. The ability of plant extracts at 2.5 mg/mL to inhibit BuChE and AChE was compared with that for galantamine at 0.01 mg/mL. Results are expressed as means ± SEM, for an n-number of 4.
Figure 4
Figure 4
DPPH radical scavenging activity of plant extracts. The ability of plant extracts across a concentration range of 12.5–200 µg/mL to scavenge the DPPH• was assessed spectrophotometrically and compared with Vitamin E. Histograms represent means ± SEM for an n-number of 4; ns = nonsignificant differences from Vitamin E.
Figure 5
Figure 5
Toxicity of plant extracts to SH-SY5Y neuroblastoma cells. Cultured SH-SY5Y cells were exposed to plant extracts over a concentration range of 156–2500 µg/mL and for 48 h. Toxicity was evaluated by a MTT assay. Histograms represent cell viability as means ± SEM for an n-number of 4; ns = nonsignificant differences from control values.
Figure 6
Figure 6
Correlation analysis between anti-cholinesterase activities, DPPH radical scavenging, and cell viability for plant extracts. (A) Correlation between BuChE and AChE potency. (B) Correlation between DPPH radical scavenging and AChE inhibition. (C) Correlation between DPPH radical scavenging and BuChE inhibition. (D) Correlation between cell viability and AChE inhibition. (E) Correlation between cell viability and BuChE inhibition. (F) Correlation between cell viability and DPPH radical scavenging.
Figure 7
Figure 7
Molecular docking of potential ChEIs. (a) Binding pose of 3-caffeoylquinic acid (pink-colored sticks) looking down the gorge of AChE (green-colored surface representation). (b) The 3-caffeoylquinic acid (pink-colored sticks) docked with binding site residues of AChE (green-colored sticks). (c) Binding pose of rutin (pink-colored sticks) looking down the gorge of BuChE (green-colored surface representation). (d) Rutin (pink-colored sticks) docked with binding site residues of BuChE (green-colored sticks). Hydrogen bonding represented by yellow lines.
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