Publications by authors named "Mathieu P A Hébert"

3 Publications

  • Page 1 of 1

Evaluating the mitochondrial activity and inflammatory state of dimethyl sulfoxide differentiated PLB-985 cells.

Mol Immunol 2021 Apr 7;135:1-11. Epub 2021 Apr 7.

Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada; New Brunswick Center for Precision Medicine, Moncton, NB, Canada. Electronic address:

Neutrophils play a key role in the innate immunity with their ability to generate and release inflammatory mediators that promote the inflammatory response and consequently restore the hemostasis. As active participants in several steps of the normal inflammatory response, neutrophils are also involved in chronic inflammatory diseases such as asthma, atherosclerosis, and arthritis. Given their dual role in the modulation of inflammation, regulating the inflammatory response of neutrophils has been suggested as an important therapeutic approach by numerous researchers. The neutrophils have a relatively short lifespan, which can be problematic for some in vitro experiments. To address this issue, researchers have used the human monomyelocyte cell line PLB-985 as an in vitro model for exploratory experiments addressing neutrophil-related physiological functions. PLB-985 cells can be differentiated into a neutrophil-like phenotype upon exposure to several agonists, including dimethyl sulfoxide (DMSO). Whether this differentiation of PLB-985 affects important features related to the neutrophil's normal functions (i.e., mitochondrial activity, eicosanoid production) remains elusive, and characterizing these changes will be the focal point of this study. Our results indicate that the differentiation affected the proliferation of PLB-985 cells, without inducing apoptosis. A significant decrease in mitochondrial respiration was observed in differentiated PLB-985 cells. However, the overall mitochondria content was not affected. Immunoblotting with mitochondrial antibodies revealed a strong modulation of the succinate dehydrogenase A, superoxide dismutase 2, ubiquinol-cytochrome c reductase core protein 2 and ATP synthase subunit α in differentiated PLB-985 cells. Finally, eicosanoids (leukotriene B, 12-hydroxyheptadecatrienoic and 15-hydroxyeicosatetraenoic acids) production was significantly increased in differentiated cells. In summary, our data demonstrate that the differentiation process of PLB-985 cells does not impact their viability despite a reduced respiratory state of the cells. This process is also accompanied by modulation of the inflammatory state of the cell. Of importance, our data suggest that PLB-985 cells could be suitable in vitro candidates to study mitochondrial-related dysfunctions in inflammatory diseases.
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http://dx.doi.org/10.1016/j.molimm.2021.03.026DOI Listing
April 2021

New Zileuton-Hydroxycinnamic Acid Hybrids: Synthesis and Structure-Activity Relationship towards 5-Lipoxygenase Inhibition.

Molecules 2020 Oct 14;25(20). Epub 2020 Oct 14.

Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB E1A3E9, Canada.

A novel series of zileuton-hydroxycinnamic acid hybrids were synthesized and screened as 5-lipoxygenase (5-LO) inhibitors in stimulated HEK293 cells and polymorphonuclear leukocytes (PMNL). Zileuton's () benzo[b]thiophene and hydroxyurea subunits combined with hydroxycinnamic acid esters' ester linkage and phenolic acid moieties were investigated. Compound , bearing zileuton's () benzo[b]thiophene and sinapic acid phenethyl ester's () α,β-unsaturated phenolic acid moiety was shown to be equipotent to zileuton (), the only clinically approved 5-LO inhibitor, in stimulated HEK293 cells. Compound was three times as active as zileuton () for the inhibition of 5-LO in PMNL. Compound , bearing the same sinapic acid (3,5-dimethoxy-4-hydroxy substitution) moiety as , combined with zileuton's () hydroxyurea subunit was inactive. This result shows that the zileuton's () benzo[b]thiophene moiety is essential for the inhibition of 5-LO product biosynthesis with our hydrids. Unlike zileuton (), Compound formed two π-π interactions with Phe177 and Phe421 as predicted when docked into 5-LO. Compound was the only docked ligand that showed a π-π interaction with Phe177 which may play a part in product specificity as reported.
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http://dx.doi.org/10.3390/molecules25204686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587396PMC
October 2020

Extraction, Antioxidant Capacity, 5-Lipoxygenase Inhibition, and Phytochemical Composition of Propolis from Eastern Canada.

Molecules 2020 May 21;25(10). Epub 2020 May 21.

Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB E1A 3E9, Canada.

Soxhlet (SE), microwave-assisted (MAE) and ultrasound-assisted (UAE) extraction were compared using ten extraction solvents for their efficiency to extract phenolic and flavonoid antioxidants from Eastern Canada propolis. Extracts were compared for total phenolic (TPC) and total flavonoid (TFC) content, and radical scavenging activities. Anti-inflammatory activity through inhibition of 5-lipoxygenase (5-LO) products biosynthesis in HEK293 cells was also evaluated. The results showed that SE extracts using polar solvents had the highest TPC and TFC. Extracts obtained with ethanol, methanol and acetone were effective free radical scavengers, and showed 5-LO inhibition similar to zileuton. UAE was an effective extraction method since the extracts obtained were comparable to those using SE and the MAE while being done at room temperature. With UAE, extracts of less polar solvents showed similar free radical scavenging and 5-LO inhibition to extracts of much more polar solvents such as methanol or ethanol. Reversed-phase liquid chromatography tandem mass spectrometry confirmed the presence of 21 natural compounds in the propolis extracts based on the comparison of intact mass, chromatographic retention time and fragmentation patterns derived from commercial analytical standards. The current study is the first of its kind to concurrently investigate solvent polarity as well as extraction techniques of propolis.
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http://dx.doi.org/10.3390/molecules25102397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287732PMC
May 2020