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A Major Diplotaxis harra-Derived Bioflavonoid Glycoside as a Protective Agent against Chemically Induced Neurotoxicity and Parkinson’s Models; In Silico Target Prediction; and Biphasic HPTLC-Based Quantification
Oxidative stress and chronic inflammation have a role in developing neurodegenerative diseases such as Parkinson’s disease (PD) and inflammatory movement disorders such as rheumatoid arthritis that affect millions of populations. In searching for antioxidant and anti-inflammatory molecules from natu...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912516/ https://www.ncbi.nlm.nih.gov/pubmed/35270118 http://dx.doi.org/10.3390/plants11050648 |
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author | Ahmed, Atallah F. Wen, Zhi-Hong Bakheit, Ahmed H. Basudan, Omer A. Ghabbour, Hazem A. Al-Ahmari, Abdullah Feng, Chien-Wei |
author_facet | Ahmed, Atallah F. Wen, Zhi-Hong Bakheit, Ahmed H. Basudan, Omer A. Ghabbour, Hazem A. Al-Ahmari, Abdullah Feng, Chien-Wei |
author_sort | Ahmed, Atallah F. |
collection | PubMed |
description | Oxidative stress and chronic inflammation have a role in developing neurodegenerative diseases such as Parkinson’s disease (PD) and inflammatory movement disorders such as rheumatoid arthritis that affect millions of populations. In searching for antioxidant and anti-inflammatory molecules from natural sources that can counteract neurodegenerative diseases and arthritis, the flavonoid-rich extract of Diplotaxis harra (DHE) was selected based on its in vitro antioxidant and anti-inflammatory activities. DHE could inhibit the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages from 100% to the level of 28.51 ± 18.67 and 30.19 ± 5.00% at 20 μg/mL, respectively. A TLC bioautography of DHE fractions using 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) led to the isolation of a major antioxidant compound which was identified by X-ray diffraction analysis as isorhamnetin-3-O-β-D-glucoside (IR3G). IR3G also exhibited a potent anti-inflammatory activity, particularly by suppressing the upregulation of iNOS expression, similar to that of dexamethasone (DEX) at 10 μM to the level of 35.96 ± 7.80 and 29.34 ± 6.34%, respectively. Moreover, IR3G displayed a strong neuroprotectivity (>60% at 1.0(−4)–1.0(−3) μM) against 6-hydroxydopamine (6-OHDA)-challenged SHSY5Y neuroblastoma, an in vitro model of dopaminergic neurons for Parkinson’s disease (PD) research. Accordingly, the in vivo anti-Parkinson potentiality was evaluated, where it was found that IR3G successfully reversed the 6-OHDA-induced locomotor deficit in a zebrafish model. A study of molecular docking and molecular dynamic (MD) simulation of IR3G and its aglycone isorhamnetin (IR) against human acetylcholine esterase (AChE), monoamine oxidase B (MAO-B), and Polo-like kinase-2 (PLK2) was performed and further outlined a putative mechanism in modulating neurodegenerative diseases such as PD. The free radical scavenging, anti-inflammatory through anti-iNOS and anti-COX-2 expression, and neuroprotective activities assessed in this study would present partial evidence for the potentiality of D. harra-derived IR3G as a promising natural therapeutic agent against neurodegenerative diseases and inflammatory arthritis. Finally, a biphasic HPTLC method was developed to estimate the biomarker IR3G in D. harra quantitatively. |
format | Online Article Text |
id | pubmed-8912516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89125162022-03-11 A Major Diplotaxis harra-Derived Bioflavonoid Glycoside as a Protective Agent against Chemically Induced Neurotoxicity and Parkinson’s Models; In Silico Target Prediction; and Biphasic HPTLC-Based Quantification Ahmed, Atallah F. Wen, Zhi-Hong Bakheit, Ahmed H. Basudan, Omer A. Ghabbour, Hazem A. Al-Ahmari, Abdullah Feng, Chien-Wei Plants (Basel) Article Oxidative stress and chronic inflammation have a role in developing neurodegenerative diseases such as Parkinson’s disease (PD) and inflammatory movement disorders such as rheumatoid arthritis that affect millions of populations. In searching for antioxidant and anti-inflammatory molecules from natural sources that can counteract neurodegenerative diseases and arthritis, the flavonoid-rich extract of Diplotaxis harra (DHE) was selected based on its in vitro antioxidant and anti-inflammatory activities. DHE could inhibit the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages from 100% to the level of 28.51 ± 18.67 and 30.19 ± 5.00% at 20 μg/mL, respectively. A TLC bioautography of DHE fractions using 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) led to the isolation of a major antioxidant compound which was identified by X-ray diffraction analysis as isorhamnetin-3-O-β-D-glucoside (IR3G). IR3G also exhibited a potent anti-inflammatory activity, particularly by suppressing the upregulation of iNOS expression, similar to that of dexamethasone (DEX) at 10 μM to the level of 35.96 ± 7.80 and 29.34 ± 6.34%, respectively. Moreover, IR3G displayed a strong neuroprotectivity (>60% at 1.0(−4)–1.0(−3) μM) against 6-hydroxydopamine (6-OHDA)-challenged SHSY5Y neuroblastoma, an in vitro model of dopaminergic neurons for Parkinson’s disease (PD) research. Accordingly, the in vivo anti-Parkinson potentiality was evaluated, where it was found that IR3G successfully reversed the 6-OHDA-induced locomotor deficit in a zebrafish model. A study of molecular docking and molecular dynamic (MD) simulation of IR3G and its aglycone isorhamnetin (IR) against human acetylcholine esterase (AChE), monoamine oxidase B (MAO-B), and Polo-like kinase-2 (PLK2) was performed and further outlined a putative mechanism in modulating neurodegenerative diseases such as PD. The free radical scavenging, anti-inflammatory through anti-iNOS and anti-COX-2 expression, and neuroprotective activities assessed in this study would present partial evidence for the potentiality of D. harra-derived IR3G as a promising natural therapeutic agent against neurodegenerative diseases and inflammatory arthritis. Finally, a biphasic HPTLC method was developed to estimate the biomarker IR3G in D. harra quantitatively. MDPI 2022-02-27 /pmc/articles/PMC8912516/ /pubmed/35270118 http://dx.doi.org/10.3390/plants11050648 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ahmed, Atallah F. Wen, Zhi-Hong Bakheit, Ahmed H. Basudan, Omer A. Ghabbour, Hazem A. Al-Ahmari, Abdullah Feng, Chien-Wei A Major Diplotaxis harra-Derived Bioflavonoid Glycoside as a Protective Agent against Chemically Induced Neurotoxicity and Parkinson’s Models; In Silico Target Prediction; and Biphasic HPTLC-Based Quantification |
title | A Major Diplotaxis harra-Derived Bioflavonoid Glycoside as a Protective Agent against Chemically Induced Neurotoxicity and Parkinson’s Models; In Silico Target Prediction; and Biphasic HPTLC-Based Quantification |
title_full | A Major Diplotaxis harra-Derived Bioflavonoid Glycoside as a Protective Agent against Chemically Induced Neurotoxicity and Parkinson’s Models; In Silico Target Prediction; and Biphasic HPTLC-Based Quantification |
title_fullStr | A Major Diplotaxis harra-Derived Bioflavonoid Glycoside as a Protective Agent against Chemically Induced Neurotoxicity and Parkinson’s Models; In Silico Target Prediction; and Biphasic HPTLC-Based Quantification |
title_full_unstemmed | A Major Diplotaxis harra-Derived Bioflavonoid Glycoside as a Protective Agent against Chemically Induced Neurotoxicity and Parkinson’s Models; In Silico Target Prediction; and Biphasic HPTLC-Based Quantification |
title_short | A Major Diplotaxis harra-Derived Bioflavonoid Glycoside as a Protective Agent against Chemically Induced Neurotoxicity and Parkinson’s Models; In Silico Target Prediction; and Biphasic HPTLC-Based Quantification |
title_sort | major diplotaxis harra-derived bioflavonoid glycoside as a protective agent against chemically induced neurotoxicity and parkinson’s models; in silico target prediction; and biphasic hptlc-based quantification |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912516/ https://www.ncbi.nlm.nih.gov/pubmed/35270118 http://dx.doi.org/10.3390/plants11050648 |
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