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Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from Myrtus Communis on Inflammatory Response in Mouse Macrophages

(1) Introduction: Reactive oxygen species (ROS) and nitric oxide (NO) are key signaling molecules that play important roles in the progression of inflammatory disorders. The objective of this study was to explore the use of myrtucommuacetalone-1 (MCA-1), as a novel compound of natural origin and a p...

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Autores principales: Soomro, Samreen, Mesaik, M. Ahmed, Shaheen, Farzana, Khan, Noureen, Halim, Sobia Ahsan, Ul-Haq, Zaheer, Ali Siddiqui, Rafat, Choudhary, Muhammad Iqbal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983223/
https://www.ncbi.nlm.nih.gov/pubmed/31861488
http://dx.doi.org/10.3390/molecules25010013
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author Soomro, Samreen
Mesaik, M. Ahmed
Shaheen, Farzana
Khan, Noureen
Halim, Sobia Ahsan
Ul-Haq, Zaheer
Ali Siddiqui, Rafat
Choudhary, Muhammad Iqbal
author_facet Soomro, Samreen
Mesaik, M. Ahmed
Shaheen, Farzana
Khan, Noureen
Halim, Sobia Ahsan
Ul-Haq, Zaheer
Ali Siddiqui, Rafat
Choudhary, Muhammad Iqbal
author_sort Soomro, Samreen
collection PubMed
description (1) Introduction: Reactive oxygen species (ROS) and nitric oxide (NO) are key signaling molecules that play important roles in the progression of inflammatory disorders. The objective of this study was to explore the use of myrtucommuacetalone-1 (MCA-1), as a novel compound of natural origin and a potential anti-inflammatory agent. (2) Methodology: The anti-inflammatory potential of MCA-1, which was isolated from Myrthus communis Linn, was determined by assaying superoxide, hydrogen peroxide, and nitric oxide production in macrophages. Furthermore, the effects of the compound were analyzed via phosphorylation and translocation of the transcription factor NF kappa B, which is a key regulator of iNOS activation. The effect of MCA-1 on the inducible nitric oxide synthase (iNOS) enzyme was also examined using in silico docking studies. The anticancer potential for MCA-1 was evaluated with an MTT cytotoxic assay. (3) Results: In stimulated macrophages, MCA-1 inhibited superoxide production by 48%, hydrogen peroxide by 53%, and nitric oxide (NO) with an IC(50) of <1 µg/mL. MCA-1 also showed a very strong binding pattern within the active site of the inducible nitric oxide synthase enzyme. Furthermore, 25 µg/mL of MCA-1 inhibited inducible nitric oxide synthase expression and abolished transcription factor (NFκB) phosphorylation and translocation to the nucleus. Cytotoxicity analyses of MCA-1 on 3T3 mouse fibroblasts, CC1 liver cell line, J774.2, macrophages and MDBK bovine kidney epithelial cell, yielded IC(50) values of 6.53 ± 1.2, 4.6 ± 0.7, 5 ± 0.8, and 4.6 ± 0.7, µg/mL, respectively. (4) Conclusion: Our results suggest that MCA-1, a major phloroglucinol-type compound, shows strong anti-inflammatory activity and has a potential to be a leading therapeutic agent in the future.
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spelling pubmed-69832232020-02-06 Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from Myrtus Communis on Inflammatory Response in Mouse Macrophages Soomro, Samreen Mesaik, M. Ahmed Shaheen, Farzana Khan, Noureen Halim, Sobia Ahsan Ul-Haq, Zaheer Ali Siddiqui, Rafat Choudhary, Muhammad Iqbal Molecules Article (1) Introduction: Reactive oxygen species (ROS) and nitric oxide (NO) are key signaling molecules that play important roles in the progression of inflammatory disorders. The objective of this study was to explore the use of myrtucommuacetalone-1 (MCA-1), as a novel compound of natural origin and a potential anti-inflammatory agent. (2) Methodology: The anti-inflammatory potential of MCA-1, which was isolated from Myrthus communis Linn, was determined by assaying superoxide, hydrogen peroxide, and nitric oxide production in macrophages. Furthermore, the effects of the compound were analyzed via phosphorylation and translocation of the transcription factor NF kappa B, which is a key regulator of iNOS activation. The effect of MCA-1 on the inducible nitric oxide synthase (iNOS) enzyme was also examined using in silico docking studies. The anticancer potential for MCA-1 was evaluated with an MTT cytotoxic assay. (3) Results: In stimulated macrophages, MCA-1 inhibited superoxide production by 48%, hydrogen peroxide by 53%, and nitric oxide (NO) with an IC(50) of <1 µg/mL. MCA-1 also showed a very strong binding pattern within the active site of the inducible nitric oxide synthase enzyme. Furthermore, 25 µg/mL of MCA-1 inhibited inducible nitric oxide synthase expression and abolished transcription factor (NFκB) phosphorylation and translocation to the nucleus. Cytotoxicity analyses of MCA-1 on 3T3 mouse fibroblasts, CC1 liver cell line, J774.2, macrophages and MDBK bovine kidney epithelial cell, yielded IC(50) values of 6.53 ± 1.2, 4.6 ± 0.7, 5 ± 0.8, and 4.6 ± 0.7, µg/mL, respectively. (4) Conclusion: Our results suggest that MCA-1, a major phloroglucinol-type compound, shows strong anti-inflammatory activity and has a potential to be a leading therapeutic agent in the future. MDPI 2019-12-18 /pmc/articles/PMC6983223/ /pubmed/31861488 http://dx.doi.org/10.3390/molecules25010013 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Soomro, Samreen
Mesaik, M. Ahmed
Shaheen, Farzana
Khan, Noureen
Halim, Sobia Ahsan
Ul-Haq, Zaheer
Ali Siddiqui, Rafat
Choudhary, Muhammad Iqbal
Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from Myrtus Communis on Inflammatory Response in Mouse Macrophages
title Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from Myrtus Communis on Inflammatory Response in Mouse Macrophages
title_full Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from Myrtus Communis on Inflammatory Response in Mouse Macrophages
title_fullStr Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from Myrtus Communis on Inflammatory Response in Mouse Macrophages
title_full_unstemmed Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from Myrtus Communis on Inflammatory Response in Mouse Macrophages
title_short Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from Myrtus Communis on Inflammatory Response in Mouse Macrophages
title_sort inhibitory effects of myrtucommuacetalone 1 (mca-1) from myrtus communis on inflammatory response in mouse macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983223/
https://www.ncbi.nlm.nih.gov/pubmed/31861488
http://dx.doi.org/10.3390/molecules25010013
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